307 - ksos · 2011. 7. 2. · m.d., 7th edition 4. atlas of glaucoma, neil t choplin, diane c...

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Editorial

Glaucoma is generally described as the silent thief of sight. Last few years have witnessed some major changes in the outlook of management of glaucoma. Some important clinical trials have given more insight into the treatment of glaucoma. This issue of KJO is dedicated to this subspecialty in ophthalmology.

Even though with effective treatment blindness can be delayed in most cases of glaucoma, some are very refractory to treatment. Aqueous drainage devices are useful in this scenario. Different types of shunts especially Indian made ones are described in the first article. Another difficult situation is paediatric glaucoma. Second article describes the difficulties faced and the methods to overcome them while managing childhood glaucoma. Surgical methods are also explained. Non penetrating glaucoma filtering surgery and selective laser trabeculoplasty are two relatively new concepts. These topics are covered with current evidence in support to them.

In a case of glaucoma associated with cataract management options are little confusing. It is a dilemma for most of us to recognize the sequence of events that will be ideal while managing cataract with glaucoma. The review article on co existent glaucoma and cataract gives some simple algorithms for managing this situation. Current literature is reviewed in support of the arguments. Another surgical situation is pseudo exfoliation syndrome. This is associated with a high incidence of intraoperative complications during cataract extraction. The review on pseudo exfoliation glaucoma will be useful for all the practicing ophthalmologists. Another article that will be very useful for general ophthalmologist is an article which tells you how to calibrate an applanation tonometer which is used in routine practice by all of us. Illustrations make the steps very simple.

We have two original articles on the surgical outcome of glaucoma cases. Split macular fixation is a nightmare for any glaucoma surgeon because of the theoretical chance of wipe out. Also outcome of cases of uncontrolled glaucoma requiring surgery is unpredictable. The articles conclude with a positive note saying that all is not that bad and the chance of wipe out is not very high. It is better to operate where majority of cases benefit rather than observing the patient go blind. The brief communication tells about a new relation or co existence between sleep apnoea and glaucoma. Whether it is a co incidence or whether there is any significant correlation between these two conditions or whether sleep apnea is an independent risk factor for glaucoma will be elucidated by larger studies in future. Another original article discusses the relation of diabetic retinopathy and plasma fibrinogen. The clinical significance of this is not clear at present. Also it may have some implications in the management of sight threatening diabetic retinopathy in future.

We continue all the regular features like journal and book reviews, spot diagnosis and PG corner. The response of theme based journal had been very encouraging. Issues of KJO like last one based on trauma may be used as a quick reference. Editorial board feels this issue may also be useful to all the members of KSOS. Ultimately the aim of painstakingly bringing out the journal is to impart and spread the knowledge. Editorial office is taking steps to improve so that KJO gets better and better.

Mahesh G

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MajorReview Aqueous Drainage Devices

Address for Correspondance: VV Associates, II Sringaram Avenue, 85, Pantheon Road, Egmore, Chennai-8

These are specially deviced plates with tubes which conduct aqueous from the anterior chamber to the subtenon lake created at the equator. Aqueous drainage devices are important tools in the management of refractory glaucomas.

Seton(Latin word - bristle)

Seton is a non- hollow linear shaft that prevents wound apposition facilitating bulk flow by surface tension.

Sources of Seton: Silk, Horse hair, gold, Tantalum wire, platinum, gelatin, Silicon, PMMA.

Shunt

Shunt is a passive tubular structure incapable of influencing either antegrade or retrograde flow.

Valves

Designed to allow unidirectional flow.

Principle

Principle behind the function of the aqueous drainage devices is that it provides an alternate pathway for drainage and absorption of aqueous. Aqueous is shunted to a subscleral lake created behind the equator where the plate is fixed and aqueous collected there is absorbed in to systemic circulation by diffusion and through the scleral veins.

Basic fundamentals of drainage implants

All modern implants are made of non reactive synthetic material to which fibroblasts adhere poorly. Device establishes a potential space around which drained aqueous is pooled and gets absorbed. The bleb is placed away from the anterior limbus and this reduces inflammation and thinning of the bleb. Plates have large surface area and hence promote the formation of filtering bleb posteriorly near the equator.

Newer implants use translimbal aqueous drainage from anterior limbus to posterior subtenon reservoir. There is increased surface area under the Tenon’s causing increased absorption of aqueous and reduction in IOP. There is also a reduced possibility of conjunctival erosion.

Indications1. Refractory neovascular glaucomas2. Aphakic & pseudophakic glaucomas3. In children with JRA and uveitic glaucomas4. Post traumatic glaucomas5. Glaucomas following Vitreoretinal surgeries and PKP

6. Refractory glaucomas after failed AG surgery with or without antimetabolite7. Post inflammatory glaucomas8. ICE syndrome.

Types of Aqueous drainage devicesA. Non valved implantsB. Valved implantsC. Implants for non penetrating deep sclerectomy.

Non valved implants1. Molteno2. Bareveldt3. Schocket4. White pump shunt5. Express miniature glaucoma shunt6. istent from glaucos7. Deep light gold micro shunt from SOLX (suprachoroidal shunt)

Valved implants1. Krupin Denver2. Joseph3. American glaucoma valve4. Optimed implant5. Ahmed implant6. Keiki Mehta valve

Parts of the valveA. Connecting tubeB. Reservoir plateC. Membrane valve- Present at the junction of tube and the plate

Advantages of the valved implants are that they are pressure dependent. Start shunting of fluid only when the IOP goes above the preset level. Normally the pressure is kept at 9-10 mmHg and hence the risk of hypotony is reduced.

Implants for non penetrating deep sclerectomyAbsorbable implants1. Aquaflow- Collagen implant2. SK gel 3.5 & 4.5 implant- Reticulated Sodium Hyaluronate3. Healon GV

Non Absorbable implants1. TFLUX implant. T- shaped implant made of polymagma.2. TBAR- Made of surgical grade Stainless steel3. MERMOUD X- Essentially a PMMA implant.4. Mehta hema wedge

These implants have been used in the intra scleral space to

V. Velayutham MS

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prevent inevitable fibrosis in late stages and thereby good results are achieved.

Procedure

All procedures are done under peribulbar anaesthesia Conjunctival peritomy is done and tenon’s tissue is separated at the site of reservoir plate to be placed. Partial thickness scleral flap is taken to place the tube. The tube can also be placed through the scleral tunnel created by 18G needle. First reservoir plate is sutured in place then connecting tube is interiorized into the anterior chamber through the scleral flap/tunnel created. Tube placed inside should be bevel up and should be near the root of the iris to avoid corneal erosion.

Complications

1) Intraoperative:

• Oversized anterior chamber incision- managed by closing the wound with sutures.

• Improper direction of entry insertion- managed by redirecting the new incision.

• Scleral perforation- managed by applying retinal cryo at the perforation site.

2) Post Operative complications:

• Valve malfunction- priming should be done

• Flat chamber & Hypotony

a. By overfiltration- valved device , temporary occlusion of tube lumen with stent, injection of dense Viscoelastic agents.

b. Hypotony due to aqueous leakage around the shunt. Ensure the entry site is watertight around the shunt.

c. Flat chamber with shunt cornea touch- Early reformation of anterior chamber and correction of overdrainage by using shunt occlusion technique.

d. Flat chamber due to serous choroidal detachment and supra choroidal haemorrhage- Conservative management.

• Shunt occlusion & increased IOP: avoid by beveling the shunt away from uveal tissue or vitreous. Iridectomy at the site of tube ostium has been recommended to prevent iris plugging the tube ostium.

• Shunt Cornea Touch: Avoid making the anterior chamber insertion parallel with the iris plane.

• Shunt Exposure Or Erosion: Repair shunt exposure by removing any protruding sutures and secure the tube tightly.

• Plate Migration- Surgical Revision: Avoid by securing the plate tightly to sclera with non absorbable sutures. Plate migration towards the limbus requiresrepositioning of the

plate in te equatorial subconjunctival space. Plate migration away from the limbus may require tube extender.

• Endophthalmitis: In the late postoperative period exposure of the tube seems to be a major risk factor for these infections. Surgical revision with a patch graft in all cases is indicated to prevent this potentially devastating complication.

• Inflammation-Corticosteroids

• Diplopia-Prisms , removal of the implant

A study was conducted in RIOGOH- Chennai wherein Mehta valve implantation was done in 30 eyes of 29 patients during the two year study period between September 2006 & October 2008. The Male to Female ratio was 2:1 and the mean age was 10-64 years. The mean preop IOP was 37.4mmHg.

GLAUCOMA DIAGNOSIS NO. OF PATIENTS

Neovascular Glaucoma 22

Post traumatic Glaucoma. 2

Post PKP Glaucoma 1

Failed Trabeculectomy 2

Post inflammatory Glaucoma 3

In the immediate post operative period IOP was recorded by non- contact tonometry. 22 patients had post operative IOP well within the desired range 3 patients had minimal hyphaema in the immediate post operative period & the IOP was not recordable immediately but 1 week later the IOP was within the desired range. All cases were done without patch graft and tube was secured in the intrascleral tunnel.

In terms of IOP control Mehta implant was found to be good in refractory glaucomas and the fall in IOP was sustained over the period of follow up. Nevertheless longer follow up is necessary to examine the long term course of the success rate.

Molteno Valve

V. Velayutham - Aqueous Drainage Devices

Vol. XXII, No.4, Dec. 2010

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Kerala Journal of Ophthalmology

Ahmed Valve

Keiki Mehta Valve

iSTENT

Express Shunt

References1. Text book of Glaucoma, M. Bruce Shields, M.D. 4th edition2. The Glaucomas, Clinical Science, Robert Ritch, Theodore Krupin, M.Bruce Shields 2nd edition, Vol.2.3. Becker-Shaffer’s Diagnosic and therapy of the Glaucomas, Robert. L. Stamper, M.D., Marc F. Liberman M.D., Michael V. Drake, M.d., 7th edition4. Atlas of Glaucoma, Neil T choplin, Diane C Chandy5. Soft Section Glaucoma filtration surgry - a new technique Mehta K R, Ind J Ophthalmol. 1986:34:200

6. Wolff’s Anatomy Of the eye & Orbit , 8th Edition, Anthony T. Bron, Ramesh C. Tirupathi, Brenda J. Tripathi.

Internet References:7. Keiki Mehta BP valve Glaucoma shunt-Surgiwear8. Surgical procedure of Ahmed Glaucoma Valve9. Clinical update- Glaucoma today- Glaukos i stent10. Ocular Surgery news US edition Feb 2006- Express shunt, Solx deep light gold micro shunt, Bifurcatable trabecular shunt

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MajorReview

Glaucoma in ChildhoodA Review

Arathi Simha MS, Andrew Braganza MS, Swetha Sara Philip MS.

Address for Correspondance: Andrew Braganza, Christian Medical College, Vellore.

Introduction

Childhood or pediatric glaucomas are a heterogeneous group, comprising the true primary developmental glaucomas, associated with developmental anomalies in the eye since birth and other secondary glaucomas. Early onset primary open angle glaucoma, the so called juvenile glaucoma, as well as angle closure glaucomas both primary and secondary are also seen in the pediatric age group. Pediatric glaucoma is a potentially blinding disease accounting for about 4.2% of childhood blindness.1 Early diagnosis and prompt surgical intervention form the mainstay of management of this condition. The aim of treating pediatric glaucomas should be to lower the IOP permanently, to preserve visual acuity and field and help in the development of binocular single vision. Surgeries such as goniotomy, trabeculotomy and trabeculectomy formed the mainstay of surgical treatment and are still the commonest procedures performed today, albeit with modifications. Aqueous drainage devices and intra- and post-operative use of antimetabolites are the more significant recent advances in the surgical management of glaucoma. Medical management is only a temporizing measure while the child is awaiting surgery. However medical management does continue to play a role in older children with raised IOP or progression of glaucoma after failure or limited success of surgical procedures. Topical carbonic anhydrase inhibitors and prostaglandin analogues are the newer drugs tried in the management of paediatric glaucoma though beta blockers continue to be the most often prescribed. Continued long-term follow up and management of associated refractive errors and amblyopia are of prime importance. Early identification and prompt referral to ophthalmologists by paediatricians is very critical if functional, stable vision is to be achieved in the long term.

Classification and nomenclatureThe term developmental glaucoma refers to glaucoma that is associated with developmental anomalies in the eye since birth. It may be associated with anomalies of the anterior chamber angle and trabecular meshwork alone or associated with other ocular or systemic/developmental anomalies. Hoskin2 classified developmental glaucomas based on the anatomy/structural abnormalities as:

1) Isolated trabeculodysgenesis A Flat iris insertion • Anterior insertion • Posterior insertion

• Mixed insertion B Concave iris configuration

2) Iridotrabeculodysgenesis A anterior stromal defects • hypoplasia • hyperplasia B Anomalous iris vessels • Persistence of tunica vasculosa lentis • Anomalous superficial vessels C Structural anomalies • Holes • Colobomata • Aniridia3) Corneotrabeculodysgenesis A Peripheral ( Axenfeld anomaly) B mid peripheral (Reiger’s anomaly) C central (Peter’s anomaly)

Isolated congenital glaucoma refers to isolated trabecular maldevelopment without associated ocular or systemic anomalies. This entity has often been called primary congenital glaucoma (PCG). The terms congenital glaucoma and infantile glaucoma are often used synonymously with isolated congenital glaucoma but these could encompass other developmental glaucomas as well. Juvenile glaucoma is non-specific and is used for any type of glaucoma occurring in late childhood or teenage years for which no secondary cause is obvious. The term Juvenile Open Angle Glaucoma (JOAG) has been used to refer to chronic open angle glaucoma diagnosed between 10 to 35 years age.3 Thus, paediatric glaucoma includes developmental glaucoma as well as acquired glaucomas in children (secondary to tumors, inflammation, trauma) of which aphakic or pseudophakic glaucoma following cataract surgery is an important cause.

Epidemiology

Isolated congenital glaucoma occurs in about 1 in 30,000 live births.3 Various studies have shown varying prevalances. In India, according to a population based study in south India, the prevalence of PCG is 1 in 3,300.1 Prevalance has varied from 1 in 10,000-20,000 in the west4 to 1 in 1250 in the gypsy population of Slovakia.4 Pediatric glaucoma is a potentially blinding disease accounting for about 4.2% of childhood blindness.1 It is usually bilateral (75%) in most cases. Males constitute 65% of the cases. Most cases are sporadic. 10% show a hereditary pattern, usually autosomal recessive with variable inheritance.5


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Diagnosis and differential diagnosis

The features with which the child with congenital glaucoma could present include photophobia, epiphora, blepharospam, large eyes and hazy cornea. On examination there can be raised IOP and glaucomatous discs. The differential diagnoses for each of these symptoms and signs that have to be considered before making a diagnosis of congenital glaucoma include:

Photophobia: corneal infection, corneal epithelial defects, foreign bodies, ocular albinism

Epiphora: congenital naso-lacrimal duct block, congenital ectropion

Large cornea: megalocornea, high myopia

Hazy cornea: healed keratitis, corneal dystrophies, metabolic disorders like cystinosis congenital anomalies like Peter’s anomaly, Irido-corneo-endothelial (ICE) syndrome, Congenital Hereditary Endothelial Dystrophy (CHED)

Management

Management of a case of pediatric glaucoma begins with taking a good history regarding the onset of symptoms, treatment taken, birth history (for forceps delivery) and general activity of the child. Initial examination under sedation (Syrup trichlofos sodium- 0.75ml or 75 mg/kg body weight or Syrup chloral hydrate 25-50mg/kg body weight) to record corneal diameter, tonopen IOP and fundoscopy to evaluate disc is attempted in all children. Examination under anaesthesia with the idea of proceeding to a surgical solution is the definitive management. In older children who are cooperative for office examination, best corrected visual acuity, detailed slit-lamp examination including recording of IOP with an applanation tonometer, gonioscopy and fundus examination is done. Other tests including measurement of the corneal diameter, refraction, axial length and visual field assessment if possible should be done.

Examination under anaesthesia would include performing and documenting the following procedures:

1) Refraction (retinoscopy) if corneal clarity of either eye allows it

2) Intraocular pressure (using Tonopen or Perkins tonometer)

3) Corneal diameter – white to white (using corneal calipers)

4) Fundus examination (with indirect ophthalmoscope and 20D lenses, direct ophthalmoscope)

5) Examination of the cornea under operating microscope or, preferably, a portable slit lamp to look for Descemet’t tears or Haab’s striae. Haab’s striae are horizontal in the centre of the cornea and curvilinear at the limbus. This

kind of break has to be differentiated from breaks due to birth trauma which are more oblique or vertical.

6) Direct gonioscopy (using an indirect gonioscope and operating microscope or Koeppe’s lens with a hand held slit lamp) if the cornea is clear. In normal newborns, the trabecular meshwork(TM) is transparent and iris is inserted posterior to the scleral spur but in PCG the iris insertion is anterior and directly into the TM.6

7) Pachymetry to measure corneal thickness (using ultrasound pachymeter)

8) Axial length measurement (ultrasound)

9) B –scan (if corneal haze does not allow any view to fundus)

Choice of anaethetic agent and the stage or plane of anaesthesia during which IOP is checked is important. Cyclopropane and succinlyl choline tend to elevate the IOP giving higher values of IOP.7 A rapid lowering of intraocular pressure occurs particularly with halothane; halothane also lowers IOP artificially during deep anaesthsia.7 Agents achieving lighter anaesthesia like ketamine and diethylether are suitable agents.7 It is important to check the IOP immediately after induction as deeper stages of anesthesia will give falsely low pressure. IOP of more than 20 mmHg should be viewed with suspicion, but there is a wide variation expected with the type of anaesthetic agent, the age of the patient and the stage of anaesthesia.8 IOP values cannot be alone used for a diagnosis of glaucoma but must be interpreted with co-existing signs like corneal diameters, optic disc cupping, axial length etc.

The normal horizontal corneal diameter is approximately 10.5 to 11 mm. At birth normal horizontal corneal diameter is considered to be 10 mm, up to 10.5 mm at 6 months of age and less than 11 mm at 1year of age.9 Horizontal corneal diameter of more than 12 mm by one year of age must be treated as suspicious of glaucoma. Glaucomatous disc changes are often seen early in children; conversely, enlargement of the cup often reverses following reduction of IOP. Both phenomena are probably due to the increased elasticity of the connective tissues of the optic nerve head at this age.10 Cup-disc ratio (CDR) ≥ 0.3 and presence of asymmetry in cupping between the two eyes is suggestive of congenital glaucoma. The normal disc has a round central cup with surrounding pink healthy NRR. Normal axial length is about 22 mm by one year of age. It has been shown that nearly 90% of the growth of the eye takes place by 18 months of age and from this age to 11 years of age the eye grows by a maximum of 2 mm.11 Thereafter, the axial length of the eye stabilizes.

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Arathi Simha, Andrew Braganza et al - Glaucoma in Childhood

Therapy

In PCG the mainstay of treatment is surgery. Medical therapy is used as a temporizing measure while the child is awaiting evaluation by a paediatrician or anaesthetist to assess the child’s fitness for general anaesthesia. It reduces and stabilizes the IOP to a certain extent thus facilitating surgical intervention. However these drugs do have a role in the management of glaucoma in older children.

Medical therapy1. Beta Blockers

Timolol (0.25%), a non-selective beta–blocker, is the most commonly used medication for treatment of developmental glaucoma. It acts by reducing aqueous inflow. Side effects such as respiratory distress or apnoea, hypothermia and bradycardia are well described.12,13 Punctal occlusion should be employed after instilling timolol in the eyes to reduce systemic absorption. Selective beta blockers are safer in children.13 Betaxolol (0.25%) is a selective β1 blocker and causes less respiratory problems.14 The gel form is preferred to the purely aqueous preparation in children as gels are less absorbed systemically;15 however, these are not very easily available. Local side effects of beta blockers include ocular burning, stinging and dryness16 but are usually not so severe as to cause discontinuation.

2. Carbonic Anhydrase Inhibitors (CAI)

Oral Acetazolamide (Diamox) in the dose 5-10mg/kg body weight17 every 6 hours is safe and well tolerated in infants. Side effects from short-term use of carbonic anhydrase inhibitors (CAIs) in infants and young children are rare. However side effects of oral CAIs like diarrhoea, hypokalemia, hyponatremia, asthenia, hypochloremic acidosis, hypersensitivity reactions, renal stones and growth suppression could occur.18 Systemic side effects are less common with topical CAIs.

Topical CAI s have been shown to effectively lower IOP in children with few side effects.19,20 Systemic acidosis has been reported in a neonate on topical CAI alone.21 Dorzolamide (2%) and Brinzolamide (1%) are carbonic anhydrase inhibitors available for topical use. Dorzolamide is preferred to brinzolamide since it causes lesser ocular burning, stinging and itching.22 In a randomized controlled trial of 56 patients below 6 years of age followed up over 3 months, by Ott et al,19 IOP reduction of about 20% was noted with dordolamide 2% tid with no serious systemic side effects. Ocular discharge, ocular hyperemia and ocular burning caused discontinuation. Portellos et al20 have reported an IOP-lowering effect of 27% in a 6-month study in children. Sabri et al23 found greater addictive effect in children compared to adults when oral CAI were added compared to topical dorzolamide. However, others have found more or equal efficacy of topical CAI

s as compared to oral CAIs. Combination of the two forms is effective in reducing IOP in children more than in adults probably due to the presence of a higher level of carbonic anhydrase receptors in pediatric ocular tissue.22

3. Prostagladin analogues

Prostaglandin (PG) anlogues are found to be less effective in children compared to adults.22 The exact reason for the poor response is not clear. Variation in the outflow pathways in these children as well as the alteration in these pathways post-surgery are considered to be the possibilities for poor response.22 Late onset glaucomas with normal angles as in Sturge Weber syndrome24,25,26 as well as older children27 have been found to show better response to latanoprost). In a study by Enyedi et al,28 latanoprost reduced the IOP by only 14.7% in 8 eyes in contrast to adults where PG analogues reduce IOP by as much as 30%.

In another study29 on 57 eyes of 48 pediatric patients with uncontrolled IOP with congenital glaucoma, aphakic glaucoma, and juvenile open-angle glaucoma (JOAG), 32% had an IOP reduction of at least 10% after the addition of latanoprost, whereas only 19% had at least a 15% decrease in IOP. The median age of responders and non-responders was 11 and 5 years respectively. In addition, responders were significantly more likely to carry a diagnosis of JOAG than non-responders.

No significant side effects have been reported with PG analogues in children.30A case of uveal effusion has been reported in a child with Sturge Weber syndrome on travoprost.31 PG analogues thus possibly have a role in the management of late onset glaucoma in older children and in secondary glaucomas like aphakic and pseudophakic glaucomas in the paediatric age group.

Alpha 2 agonists (brimonidine, apraclonidine) have significant central nervous system toxic side effects like somnolence, respiratory depression and apnoea due to the drug crossing the BBB easily in neonates and children and are best avoided.22

Miotics like pilocarpine have not demonstrated much effect due to abnormal iris insertion.32 They are not currently recommended in the routine management of paediatric glaucoma.

Surgical ManagementGoniotomy

This procedure consists of incising the obstructing structures in the angle which allows separation of the trabecular sheets and subsequent flow of aqueous into Schlemm’s canal. It is done by entering the anterior chamber and sweeping the angle with a blade under direct visualization using an indirect


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gonioscope such as a Barkan lens under the operating microscope. The conjunctiva is not opened. It can be done only in clear corneas where angle visualization is possible. Shaffer33 reported a success rate of 94% with goniotomy in children aged between 1 and 24 months. The outcome was poorer in neonates less than 1 month (26%) as well as in children older than 2 years (38%). The main inhibition to using this procedure is that most paediatric glaucomas in our country are seen at an advanced stage when the cornea is hazy. Further, lack of experience with the technique means that this is a rarely used surgical option.

Trabeculotomy

In this procedure, a trabeculotome is inserted from the external aspect under a partial thickness scleral flap and incision into Schlemm’s canal and swept across the angle with the inner blade of the trabeculotome entering the anterior chamber. As with goniotomy the aim is to remove the obstruction to aqueous outflow across the anomalous angle. The advantage over goniotomy is that the procedure can be done irrespective of corneal clarity. However, considerable expertise by the surgeon is required. Success rates of 80-90%34 have been reported. Hyphaema, stripping of Descemet’s membrane and iridodialysis are some of the associated complications.

Ikeda et al35 in a study of 112 eyes with primary developmental glaucoma with trabeculectomy followed up over 9.5 ± 7.1 years, reported good long term success of 89.3% with trabeculotomy.

Debnath et al36 in a retrospective study compared trabeculotomy (31 eyes of 16 children) with trabeculectomy (30 eyes of 16 children) and found success of 67% and 54% respectively. The difference was not statistically significant. Trabeculectomy was associated with more complications.

Tamcelik et al37 compared viscotrabeculotomy (group1, n=58) with standard trabeculotomy (group2, n=51) in a long term study in children with at least 3 years of follow up. At the last visit, the success rates of group 1 and group 2 were 91.3% and 68.6% respectively, and the difference was statistically significant (p = 0.02). The mean number of anti-glaucoma medications used after surgery was significantly lower in the viscotrabeculectomy group They concluded that the use of viscoelastic materials during trabeculotomy may increase the success rate of the procedure by prevention and inhibition of postoperative haemorrhage, adhesion of the incision lips and fibroblastic proliferation.

Trabeculectomy

Trabeculectomy creates a fistula draining aqueous from the anterior chamber into the subconjunctival space and bypasses episcleral venous pressure. Thus, combining a trabeculotomy and trabeculectomy would work through

separate mechanisms and produce additional lowering of IOP. Trabeculectomy in children has lower success rates due to the thick Tenon’s capsule and exaggerated healing. There are varying reports of success (50% to over 90%) of trabeculectomy in paediatric glaucoma depending on the definition of success, length of follow up and variations in surgical techniques.

Table 1

* Clinics (Sao Paulo). 2008;63(4):421-6. # JPOS 2005 ;42;97-102$ BJO 2005 ; 89(2) 165-168**Ophthalmology 1997;104:996-1001##JGlaucoma 1995;4:151-157

Beauchamp et al38 (n=26) reported overall success of 50% in controlling IOP. Burke et al39 (n= 21) reported 87% success, Rao et al40 (n=25) 75% success and Debnath et al36 (n=30 ) 54% success. Fulcher et al41 reported success of 92.3% with trabeculectomy in primary infantile glaucoma. Detry Morel

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et al42 (n=46) reported success rates of almost 90% following trabeculectomy as the initial procedure of choice.

There are numerous studies looking at the safety and efficacy of antimetabolites in congenital glaucoma. Some studies have found more bleb related complications while other studies have not. Table 1 summarises some relevant studies of trabeculectomy with mitomycin in paediatric glaucomas.

Rodrigues et al43 in a retrospective study of 91 patients compared success of trabeculectomy without (61) and with (30) mitomycin 0.3mg/ml for 3-4 minutes and found no difference (p = 0.97) in the success. Both age and the presence of previous trabeculotomy did not influence the success of trabeculectomy through time. The complication rate (shallow anterior chamber and hypotony) was higher among the patients who received mitomycin C (p = 0.01). There were no cases of bleb related infection. Yalvac et al44 also did not find any difference in the outcome with and without mitomycin.

Mandal et al45 in a retrospective review of refractory congenital glaucomas (n=19) undergoing mitomycin augmented trabeculectomy( 0.4 mg/ml for 3 minutes) found good success(94.74%) with no case of bleb related complications(follow up 19.52 ± 2.65 months) and considered it a viable option in failed conventional trabeculotomy.

Al-Hazmi et al46 noted that bleb related complications with the use of mitomycin C increased with age. The complication rate was 0% for eyes younger than 6 months of age to 37% for eyes after 4 yearsof age and hence additional complications could be anticipated on prolonged follow up. Children less than 2 years are probably less susceptible to the effects of MMC due to the large population of multiplying cells.

Low et al47 in a retrospective case review of 30 patients, evaluated childhood filtration surgery using releasable sutures, anti-metabolites, and bleb-needling with 5-fluorouracil (5FU). Patients had undergone either trabeculectomy or combined trabeculotomy-trabeculectomy using anti-metabolites, releasable sutures, and bleb modification was performed. There were no major or sight-threatening complications in their series; no eyes developed cystic avascular blebs or bleb-related infections.

Snir etal48 have used 5-FU alone as well as with mitomycin and found no significant drug induced complications. Up to 6 injections of 5-FU (5mg) were used.

Thus, additional use of mitomycin (0.2-0.4mg/ml for 3-4 minutes) may be beneficial in paediatric glaucomas. However complications in the form of hypotony and shallow AC are commoner with mitomycin, though the risk of bleb


related endophthalmitis is not increased in children, unlike in adults. A well planned RCT would help quantify the risks and benefits.

Trabeculectomy and trabeculotomy

Good success has been reported with combined trabeculotomy and trabeculectomy. with or without antimetaboloites. Mandal et al49,50 and Elder et al51 have reported high success of more than 90% with the combined procedure.

Mullaney et al52 in a retrospective review of 60 patients (100 eyes) with congenital glaucoma, reported a 78% success rate for combined trabeculotomy and trabeculectomy for PCG. The success dropped to 45% when associated anterior segment anomalies were present.

Al-Hazmi et al53 in a retrospective review of 532 paediateric glaucoma patients (820 eyes) compared the outcomes of goniotomy, trabeculotomy, or combined trabeculotomy-trabeculectomy with mitomycin C in children less than 1 year old with minimum 1 year post-operative follow up. They found that all three surgical procedures resulted in high success rates of 81–100% for the mild form of PCG. Eyes classified with moderate glaucoma had a 13%, 40%, and 80% success rate respectively for goniotomy, trabeculotomy, and combined trabeculotomy-trabeculectomy with mitomycin C. The success rate for severe PCG was 10% and 70% for trabeculotomy and combined surgery respectively. Combined trabeculotomy-trabeculectomy with mitomycin C (CTTM) gave the best results for moderate and severe cases of PCG. Complications were most common when the CTTM technique was undertaken (31/73 cases).

Agarwal et al54 (n=30) compared mitomycin C 0.2 mg/ml vs mitomycin C 0.4 mg/ml and found no difference in the success rates of combined trabeculectomy and trabeculotomy with the two concentrations

Aqueous drainage devices

Aqueous drainage devices are usually used in refractory glaucoma in patients in whom the other above mentioned surgeries have failed. Molteno implant, Barveldt glaucoma implant and the Ahmed Glaucoma Valve (AGV) have been used in paediatric glaucoma. Adult size implants and even double plate implants are usually suitable in paediatric patients as well due to the larger size of the globe in these children with glaucoma. Smaller sized (paediatric AGV implants) may be indicated in microphthalmic eyes. Tube-cornea touch with consequent corneal decompensation is the most common complication (5.7- 20%).55 requiring surgical repositioning of the tube. Changing dimensions due to growth and expansion of the globe and limbus leads


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AGV: Ahmed Glaucoma valve implantBGI:Baerveldt Glaucoma ImplantSP:Single plateDP:Double plate*BJO2009;93 (6) 795-798#JAAPOS 2008;12(1) 33-39$ Ophthalmology 2004;111(12):2204-2210** AJO 2003; 136:994-1000## Ophthalmology 2001; 108:614-620$$ Ophthalmology 1991;98:1042-1046*** JPOS 1991; 28:68-72

Khan et al56 in a retrospective analysis compared the survival rates of polypropylene AGV (31) and silicone (11) AGV implantation during the first 2 years of life in children with 2 years’ postoperative follow-up.They found better average survival (p = 0.001) in the silicone group ( 23.36 months; CI 20.16 to 24.00 months) compared to the polypropylene

group (19.10 months CI 16.1 to 22.12 months). Cumulative probabilities of survival at 2 years by Kaplan to Meier analysis were 90.9% and 54.8% respectively (p = 0.001) . All eyes implanted with silicone AGVs had the diagnosis of congenital glaucoma, which was independently associated with better 2-year survival. They concluded that AGV implantation in other paediatric glaucoma diagnoses is needed to determine whether or not silicone AGVs independently have a better survival after implantation in the first 2 years of life.

Cyclodestructive surgeries

Cyclodestructive procedures like cyclocryotherapy and trans scleral cyclophotocoagulation are currently considered only for symptomatic children (pain) with refractory glaucomas with no visual potential. Complications like hypotony and phthisis leading to poor cosmetic outcome need to be kept in mind.

Follow up

Follow up is a essential part of glaucoma management and is particularly important in children. The treating surgeon needs to be very clear in his mind that the aim of treatment is to provide the child with good vision that will last out its lifetime, not just control of IOP. This means that refractive errors, media opacities and other factors affecting visual development must be actively looked for, and monitoring of vision to detect amblyopia is mandatory. Repeated examinations under sedation (or EUA if required) initially monthly and if stable after 5-6 months, at less frequent intervals of 2-3 months and later every 6 months are usually needed. All the parameters as detailed earlier for EUA must be recorded every time. Additionally, visual assessment by Sheridan’s or preferential looking tests as well as ocular alignment and media clarity must be specifically assessed. High IOP and increased disc cupping indicate uncontrolled glaucoma. Enlarging corneal diameters and axial length with increasingly myopic refractions are indirect clues to inadequate IOP control. Re-surgery may be needed in as many as 20% cases.55 Appropriate refractive correction and occlusion therapy if needed for amblyopia are very essential at every stage.

Conclusion

Goniotomy and trabeculotomy have yielded good results. A combined trabeculotomy and trabeculectomy procedure has the best success. All surgeries have the best outcome in isolated congenital glaucoma. Success is lesser in other types of developmental glaucomas. Primary trabeculectomy alone without trabeculotomy is not usually preferred. Mitomycin used intraoperatively has questionable benefits with some studies reporting increased incidence of bleb related complications. Aqueous drainage devices are useful for refractory paediatric glaucomas. Silicone implants (AGV) may

to angling of the tube towards the cornea. More posterior placement of the tube, 1-2 mm behind the limbus under a partial thickness scleral flap has been recommended to avoid this problem.55

Success rates of 44-100%56 have been reported depending on the age, diagnosis, definition of success, length of follow up, type of implant.

Table 2 shows details of some of the studies with aqueous drainage devices in children

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have better success, though more data is needed to confirm this. Medical management is restricted to patients awaiting surgery. However topical CA inhibitors and PG analogues may have a role in older children or as an adjunct to partially successful surgery.

Early diagnosis, prompt surgical treatment and prolonged life long follow up with ambyopia management is necessary in all cases for optimal long term visual outcomes.

References1. Dandona L, Williams JD, Williams BC, Rao GN. Population-based assessment of childhood blindness in southern India. Arch Ophthalmol 1998; 116:545-62. The Glaucomas, Ritch R, Bruce Shields M, Krupin T ed, 2nd edition, Mosby-Year Book, Chapter 33; Epidemiology and Pathphysiology of Congenital Glaucoma. Author Christopher J Dickens, H. Dunabar Hoskins Jr. Pg 7313. The Glaucomas, Ritch R, Bruce Shields M, Krupin T ed, 2nd edition, Mosby-Year Book, Chapter 33; Epidemiology and Pathphysiology of Congenital Glaucoma. Author Christopher J Dickens, H. Dunabar Hoskins Jr. Pg 7304. Gencik A, Gencikova A, Ferak V. Population genetical aspects of primary congenital glaucoma. I. Incidence, prevalence, gene frequency, and age of onset. Hum Genet 1982; 61:193-75. Sarfarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye 2000; 14:422-86. Anderson DR: The development of the trabecular meshwork and its abnormality in primary infantile glaucoma. Trans Am Ophthalmol Soc 79: 45-485, 19817. Hass J: Principles and problems of therapy in congenital glaucoma : Invest Ophthalmol 7: 140-146, 19688. Dominguez A, Banos MS, Alvarez MG: Introcular pressure measurements in infants under general anesthesia. Am J ophthalmol 78: 110-116, 19749. Kwito ML.Surgery of infant eye . New York-Appelton-Century Crofts 1979:1110. Quigley HA: Childhood glaucoma: Results with trabeculectomy and study of reversible cupping. Ophthalmology 89: 219-225, 198211. Gordon RA, Donzis PB. Refractive development of the human eye. Arch Ophthalmol 103:785-789, 198512. McMohan CD, Hetherington Jt, Hoskins HD and Shaffer RN. Timolol and pediatric glaucoma. Ophthalmology. 88: 249-252, 198113. Oslen RJ, Bromberg BB and Zimmerman TJ. Apneic cells associated with timolol therapy in a neonate. Am J Ophthalmol 88:120-122,197914. Maris PJ Jr, Mandal AK, Netland PA. Medical therapy of pediatric glaucoma and glaucoma in pregnancy. Ophthalmol Clin North Am. 2005;18:461-46815. The safety and efficacy of Glaucoma medication in the pediatric population. Greet Coppens, Ingeborg Stalsmans, Thierry Zeyen, Ingele Casteels. J Pediatr Ophthalmol Strabismus 2009;46: 12-1816. Mc Mohan CD, Hetherington JJ, Hoskins JH, Shaffer RN. Timolol and paediatric glaucomas. Ophthalmology. 1981;88:249-252

17. The Glaucomas, Chapter 34, Diagnosis and treatment of congenital glaucoma.Chri---Dickens, Hoskins Jr pg 74718. Futagi Y, Otani K, Abe J.Growth suppression in children receiving acetazolamide with anti epileptic drugs. Pediatr Neurol.1996;15:323-32619. Ott EZ, Mills MD, Arango S, Getson AJ, Assaid CA, Adamsons IA. A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years. Arch Ophthalmol 2005; 123:1177-118620. Portellos M, Buckley EG, Freedman SF. Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma. J AAPOS.1998;2:43-4721. Morris S, Geh V, Nischal A, Sahi S, Amhed MA. Topical dorzolamide and metabolic acidosis in a neonate. Br J Ophthalmol.2003;87:1052-105322. Greet Coppens, Ingeborg Stalsmans, Thierry Zeyen, Ingele Casteels. The safety and efficacy of Glaucoma medication in the pediatric population. J Pediatr Ophthalmol Strabismus 2009;46: 12-1823. Sabri K, Levin AV.The additive effect of topical dorzolamide and systemic acetazolamide in pediatric glaucoma. J AAPOS.2006;10:464-46824. Ong T,Chia A, Nischal KK.Latanoprost in portwint stain related pediatric glaucoma. Br J Ophthalmol.2000; 87:1091-109325. Yang CB, Freedman SF, Myers JS, Buckley EG, Herndon LW, Allingham RR. Use of latanoprost in the treatment of glaucoma associate dwith Sturge-Weber syndrome. Am J Ophthalmol.1998; 126: 600-60226. Altuna JC, Greenfield DS, Wand M, etal . Latanoprost in glaucoma associated with Sturge- Weber syndrome: benefits and side effects.J Glaucoma.1999;8:199-20327. Urban B, Bakunowicz Lazarczyk A, Mrugacz M, Ozeiblo Kupczyk M. The effectiveness of latanoprost for the treatment of pediatric glaucoma. Klin Ocnza.2004; 106:243-24428. Enyedi LB, Freedman SF, Buckley EG. The effectiveness of latanoprost for the treatment of pediatric glaucoma. J AAPOS 1999; 3: 33–3929. Enyedi LB, Freedman SF, Buckley EG. Latanoprost for the treatment of pediatric glaucoma. Surv Ophthalmol.2002;47:S129-13230. Black AC, Jones S, Yanovitch TL, Enyedi LB, Stinnett SS, Freedman SF.Latanoprost in pediatric glaucoma – pediatric exposure over a decade. J AAPOS. 2009 ec;13(6):558 – 6231. Gambrelle J, Denis P, Kocaba V, Grange JD. Uveal effusion induced by topical travoprost in a patient with Sturge-Weber-Krabbe syndrome. J Fr Ophtalmol. 2008;31(9):1932. Maumenee AE: Further observations on the patho¬genesis of congenital glaucoma. Am J Ophthalmol 55: 1163¬1176, 196333. Shaffer RN. Prognosis of goniotomy in primary infantile glaucoma (trabeculodysgenesis). Trans Am Ophthalmol Soc 1982; 80:321-32534. Anderson DR.Trabeculectomy compared to goniotomy for glaucoma in children. Ophthalmology 1983; 90:80535. Ikeda H, Ishigooka H, Muto T, Tanihara H, Nagata M Long-term outcome of trabeculotomy for the treatment of developmental glaucoma.Arch Ophthalmol. 2004;122(8):1122-8



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36. Debnath SC, Teichmann KD, Salamah K Trabeculectomy versus trabeculotomy in congenital glaucoma. Br J Ophthalmol. 1989;73(8):608-1137. Tamcelik N, Ozkiris A. Long-term results of viscotrabeculotomy in congenital glaucoma: comparison to classical trabeculotomy.Br J Ophthalmol. 2008;92(1):36-938. Beauchamp GR, Parks MM.Filtering surgery in children: barriers to success.Ophthalmology. 1979;86(1):170-8039. Burke JP, Bowell R.Primary trabeculectomy in congenital glaucoma. Br J Ophthalmol. 1989;73(3):186-9040. K Vengala Rao, C Madhava Sai, BV Nagendra Babu. Trabeculectomy in congenital glaucoma. Indian Journal of Ophthalmol1984; 32 (5): 439-44041. Fulcher T, Chan J, Lanigan B, Bowell R, O’Keefe M Long-term follow up of primary trabeculectomy for infantile glaucoma.Br J Ophthalmol. 1996;80(6):499-50242. Detry-Morel M, Feron EM.Trabeculectomy in congenital glaucoma: retrospective medium and long-term results.Bull Soc Belge Ophtalmol. 1996;262:143-5143. Rodrigues AM, Júnior AP, Montezano FT, de Arruda Melo PA, Prata J Jr. Comparison between results of trabeculectomy in primary congenital glaucoma with and without the use of mitomycin C.J Glaucoma. 2004;13(3):228-3244. Yalvac HS, Nurozler A, Kohraman etal . The results of trebeculectomy with and without mitomycin c in young patients.Ophthalmologica 1998: 212:39945. Mandal AK, Walton DS, John T, Jayagandan A. Mitomycin C-augmented trabeculectomy in refractory congenital glaucoma.Ophthalmology. 1997;104(6):996-100146. al-Hazmi A, Zwaan J, Awad A, al-Mesfer S, Mullaney PB, Wheeler DT. Effectiveness and complications of mitomycin C use during pediatric glaucoma surgery.Ophthalmology. 1998;105(10):1915-20

47. Low S, Hamada S, Nischal KK. Antimetabolite and releasable suture augmented filtration surgery in refractory pediatric glaucomas. J AAPOS. 2008;12(2):166-7248. Snir M, Lusky M, Shalev B, Gaton D, Weinberger D. Mitomycin

C and 5-fluorouracil antimetabolite therapy for pediatric glaucoma

filtration surgery. Ophthalmic Surg Lasers. 2000;31(1):31-7

49. Mandal AK, Naduvilath TJ, Jayagandan A. Surgical results of

combined trabeculotomy-trabeculectomy for developmental

glaucoma.Ophthalmology. 1998;105(6):974-82.

50. Mandal AK, Bhatia PG, Gothwal VK, Reddy VM, Sriramulu P,

Prasad MS, John RK, Nutheti R, Shamanna BR. Safety and efficacy

of simultaneous bilateral primary combined trabeculotomy-

trabeculectomy for developmental glaucoma. Ind J Ophthalmol.

2002;50(1):13-9

51. Elder MJ. Combined trabeculotomy-trabeculectomy compared

with primary trabeculectomy for congenital glaucoma.Br J

Ophthalmol. 1994;78(10):745-8

52. Mullaney PB, Selleck C, Al-Awad A, Al-Mesfer S, Zwaan J.

Combined trabeculotomy and trabeculectomy as an initial

procedure in uncomplicated congenital glaucoma.Arch Ophthalmol.

1999;117(4):457-60

53. Al-Hazmi A, Awad A, Zwaan J, Al-Mesfer SA, Al-Jadaan I, Al-

Mohammed A. Correlation between surgical success rate and severity

of congenital glaucoma.Br J Ophthalmol. 2005;89(4):449-53

54. Agarwal HC, Sood NN, Sihota R, Sanga L, Honavar SG. Mitomycin-C

in congenital glaucoma.Ophthalmic Surg Lasers. 1997;28(12):979-85

55. Tanimoto SA, Brandt JD. Options in pediatric glaucoma after

angle surgery has failed. Curr Opin Ophthalmol. 2006;17(2):132-7

56. Khan AO, Al-Mobarak F. Comparison of polypropylene and

silicone Ahmed valve survival 2 years following implantation in the

first 2 years of life. Br J Ophthalmol. 2009;93(6):791-4

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MajorReview

Non-Penetrating Glaucoma Filtering Surgery-An overview

Manish Panday, MS, Ronnie George, MS

Address for Correspondance: Smt. Jadhavbai Nathmal Singhvee Glaucoma Services, Sankara Nethralaya,18, College Road, Chennai

Introduction

Trabeculectomy remains the standard surgery for intraocular pressure control for glaucoma. It involves a full thickness penetration of sclera, to allow aqueous seepage to subconjunctival space under a scleral flap. However, it carries the risk of serious bleb related complications like overfiltration, hypotony and consequent persistent choroidal detachment, shallow anterior chamber, cataract, peripheral anterior synechiae or decreased vision from hypotonous maculopathy. Moreover, bleb leaks increase the risk of bleb infection and endophthalmitis.

Interest in non penetrating glaucoma surgery (NPGS) evolved in avoiding the complications of a full thickness procedure. These techniques mainly target the outer trabecular meshwork at the site of maximum resistance to aqueous outflow. Other possible mechanisms include transscleral flow, uveoscleral outflow and opening of non functional areas of Schlemm’s canal. Various surgical techniques have been described for the same, which we try to subsequently analyze in this article.

Discussion

NPGS evolved during the late 1950’s and early 1960’s by Epstein1 and Krasnov2. However, its popularity as an effective treatment for IOP control was limited due to concurrent introduction of trabeculectomy as a relatively easier and more effective procedure to perform than NPGS. Recent renewed interest in NPGS lies in overcoming these previous drawbacks.

Surgical Techniques Deep Sclerectomy

After adequate anaesthesia, a superior rectus or corneal traction suture is placed and a fornix or limbus based conjunctival flap is created. A partial thickness (one third to half thickness) limbus based scleral flap measuring 5mmx 5 mm is dissected 1.5 mm into the clear cornea. A deeper (upto 90% depth) second scleral flap measuring 4mm x 4 mm is then dissected forwards in the plane of scleral spur and Schlemm’s canal. The Schlemm’s canal is identified and unroofed for approximately 3 mm long at the level of scleral spur. Cleavage is taken forwards between the corneal stroma and Descemet’s membrane. This deeper scleral flap is subsequently excised to form a ‘scleral lake’ for pooling of aqueous. This leads to the formation of a ‘trabeculo-Descemet’s membrane’ (TDM) as the outflow resistance for

aqueous. Evidence of flow through this TDM is mandatory at this point. To improve outflow, inner wall of Schlemm’s canal can be removed and juxtacanalicular meshwork can be gently peeled with blunt forceps. Use of mitomycin c in the scleral bed and use of space maintainer implants (Aqua flow, T Flux, SKGEL and PMMA) have been described. The scleral flap is loosely sutured with two 10-0 nylon sutures and the conjunctiva and Tenon’s capsule are closed in layers. Since deep sclerectomy involves filtration and formation of a bleb, modulation by means of postoperative 5-Fluouracil injections have been described along with Nd-YAG goniopunctue of the TDM in the postoperative phase; which converts this into a full thickness procedure.

Viscocanalostomy

As a variant of NPGS, viscocanalostomy involves injecting high viscosity viscoelastic in the Schlemm’s canal, after unroofing the Schlemm’s canal. Peeling of inner wall of Schlemm’s canal and juxtacanalicular TM is not suggested. Aqueous seepage from the TDM is thus forced to reach the ostia of Schlemm’s canal. Viscoelastic is also placed in the ‘scleral lake’ preventing collagen cross linking. The first scleral flap is tightly sutured as opposed to deep sclerectomy and thus there is no filtering bleb in this procedure. The conjunctiva and Tenon’s capsule are closed in layers.

An alternative technique of dilation of Schlemm’s canal has been described using an illuminated optical fiber microcatheter. Following exposure of Schlemm’s canal, the catheter is passed circumferentially around the Schlemm’s canal under direct visualization. High viscosity hyaluronic acid is injected to dilate the Schlemm’s canal every 2 clock hours. A 10- Nylon sutue is affixed to the end of the catheter which is subsequently withdrawn. The suture is then tied resulting in 360 degree dilation of the canal. The scleral flap and conjunctiva are subsequently closed as above.

NPGS is a more challenging surgical procedure as compared to trabeculectomy, requiring increased surgical time and a prolonged learning curve. Besides, risk of perforation of the TDM requiring conversion to conventional trabeculectomy has prompted development of alternative techniques. Recently, carbon dioxide laser (CO2 laser) has also been used for photoablation of the scleral bed after fashioning a 5x5 mm superficial scleral flap. This laser has the unique property of being absorbed by a thin layer of water. The laser beam is focused on an area overlying the Schlemm’s canal and ablation is continued till obvious percolation of aqueous through the scleral bed is seen. At this point, the residual


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trabecular meshwork is protected by the effect of laser due to aqueous percolation. Thus the chances of perforation into the anterior chamber are minimized. The superficial scleral flap is secured loosely with 10-0 Nylon sutures and the conjunctiva and Tenon’s capsule are closed in layers.

Mechanism of action

Deep Sclerectomy: Aqueous percolates through the TDM into the scleral lake and then to subconjunctival space. Resultant blebs are usually shallower and more diffuse. Alternative pathways for drainage include suprachoroidal space, via the cut ends of Schlemm’s canal and through the intrascleral bleb.

Viscocanalostomy: This procedure results in dilation of Schlemm’s canal and associated collector channels, resulting in enhanced drainage through this route. In addition, damage to endothelium of Schlemm’s canal results in communication of juxtacanalicular zone to Schlemm’s canal.

Indications and Contraindications

NPGS is usually indicated in open angle glaucomas-whether primary or secondary (especially pigmentary and pseudoexfoliative). Angle closure glaucomas are a relative contraindication as clinical decision depends on degree of synechial closure of the trabecular meshwork. Iridocorneal endothelial syndrome (ICE) and eyes with congenital or juvenile glaucomas with angle anomalies and scleral thinning are contraindications to NPGS. Neovascular glaucomas constitute an absolute contraindication due to invasion of the angle and trabeculum with neovascular vessels and subsequent loss of filtration.

The amount of IOP reduction achieved with NPGS is usually lower than that by trabeculectomy. NPGS may be more suited when target IOP is in mid to high normal range. It may be a procedure of choice in patients with high risk of choroidal haemorrhage or postoperative hypotony. Currently, evidence is lacking in regards to choice of a particular procedure for a specific patient.

Postoperative complications

In general, NPGS has been shown to be associated with fewer complications as compared to trabeculectomy. The commonest intraoperative complication is perforation of the TDM. Smaller ones causing no anterior chamber shallowing and iris prolapse can be ignored, larger ones require conversion to conventional trabeculectomy. A steep learning curve has been reported in many studies and conversion rates come down with time.

Early postoperative hypotony with a deep anterior chamber is a good prognostic indicator. IOP tends to stabilize over time. Early postoperative raised IOP may be due to insufficient leakage though TDM or may be viscoelastic

induced (in combined surgeries/ AC reformations). Nd-YAG goniopuncture can be attempted in case of insufficient leak through TDM. Rupture of the fragile TDM can also occur in case of Valsalva maneuver or by trauma/ rubbing of eyes with consequent iris prolapse and raised IOP. Peripheral anterior synechiae can also cause late raised IOP. Other reported complications include Descemet’s membrane detachments, cataract and scleral ectasia.

Outcomes of NPGS

Stegmann et al3 first reported the results of viscocanalostomy in 214 eyes of 157 black patients with open angle glaucoma. The mean baseline IOP was 47.4±13.0 mm Hg and mean postoperative IOP was 16.9±8.0 mm Hg at a follow up of 35 months. Bleb formation was seen in 5% patients with minimal complications reported. Postoperative IOP of 22 mm Hg or less was achieved in 82.7% of patients.

The ophthalmic technology assessment committee of American Academy of Ophthalmology reviewed 33 articles related to NPGS from 1968 to 2000.4 They reported a mean postoperative IOP lowering to high normal range in NPGS with fewer complications due to overfiltration and hypotony as compared to trabeculectomy with no evidence of prevention of progressive glaucomatous optic neuropathy.

In a meta-analysis of 22 studies of deep sclerectomy and 14 with viscocanalostomy from January 2000 to August 2005, Hondur A et al5 reported 48.6% patients achieving an IOP of 21 mm Hg or less with primary deep sclerectomy (without antimetabolite use/ implants), the rate of goniopuncture being from 4.6% to 40%. In contrast 51.1% patients after primary viscocanalostomy achieved a final postoperative IOP of at least 21 mm Hg after 25.6 months with goniopuncture rate from 4.1% to 56%. However, most series did not report the severity of glaucoma. The authors stressed the need for data regarding glaucoma severity, visual fields in particular and an individualized target IOP to assess the efficacy and success of any surgical therapy. These success rates would also reflect post operative bleb modulations by means of goniopuncture and antimetabolite use.

Wide variation in reported success rates are also attributed to the long learning curve as well as varied surgical techniques in NPGS. Use of implants and antimetabolites in surgery is generally reported to increase the success rates.5, 6, 7 In a prospective randomised study of 26 eyes of 13 patients with open angle glaucoma, Shaarawy et al6 reported a complete success rate of 38% in deep sclerectomy alone versus 69% in those with adjuvant collagen implant at 48 months. A complete success was defined as IOP < 21 mm Hg without medications. The mean IOP was 16 mm Hg for the former and 10 mm Hg for the latter group at 48 months.

Both deep sclerectomy and viscocanalostomy can be

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combined with cataract surgery.8.9 Moreno-Lopez M et al9

in a retrospective review of 15 eyes of 12 patients showed IOP control at median of 12 months with 80% patients having IOP <17 mm Hg following cataract surgery with deep sclerectomy.

The short term efficacy of newer techniques such as carbon dioxide laser NPGS appear promising, though long term results need to be looked for in terms of IOP control and complications.

Conclusion

In general, surgical therapy in glaucoma is resorted to in failure of medical therapy. This results from the fact that the current gold standard therapy in form of trabeculectomy may result in varied intraoperative and post operative complications. However, medical therapy over prolonged period of time may also result in conjunctival remodelling and has cost concerns. Though NPGS continues to evolve for the past 50 years and the intraocular pressure achieved is in a higher range as compared to standard trabeculectomy, it may have a role in early glaucomas where modest IOP control may be required besides avoiding complications from a full thickness procedure.

References1. Epstein E. Communications. Fibrosing response to aqueous. Its relation to glaucoma. Br J Ophthal.1959;43:641-7.2. Krasnov MM. Externalisation of Schlemm’s canal (sinusotomy) in glaucoma. Br J Ophthal.1968;52:157-61.3. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open-angle glaucoma in black African patients. J Cataract Refract Surg 1999;25:316-22.4. American Academy of Ophthalmology. Ophthalmic Technology Assessment-Nonpenetrating glaucoma surgery. Ophthalmology 2001;108:416-421.5. Hondur A, Onol M, Hasanreisoglu B. Non Penetrating Glaucoma Surgery: Meta-analysis of Recent Results. J Glaucoma 2008;17:139-146.6. Shaarawy T, Mermoud A. Deep sclerectomy in one eye vs deep sclerectomy with collagen implant in the contralateral eye of the same patient: long-term follow-up. Eye 2005;19:298-302.7. Shaarawy T, Nguyen C, Schnyder C, Mermoud A. Comparative study between deep sclerectomy with and without collagen implant, long term follow up. Br J Ophthalmol 2004;88:95-8.8. Park M, Tanito M, Nishikawa M, Hayashi K, Chichara E. Combined viscocanalostomy and cataract surgery compared with cataract surgery in Japanese patients with glaucoma. J Glaucoma 2004;13:55-61.9. Moreno-Lopez M, Perez-Alvarez MJ. Short and medium-term intraocular pressure lowering effects of combined phacoemulsification and nonpenetrating deep sclerectomy without scleral implant or antifibrotics. Arch Soc EspOftalmol 2006; 81:93–100.

Figure 1, 2, 3: After dissection of the scleral flap, the laser beam being focused at the scleral bed (red dots) and repeated applications are attempted till obvious percolation of aqueous is seen. The anterior chamber depth is maintained throughout the procedure. Note the ACM in this case.

Figure 4: Diffuse bleb 1 month postoperative with deep AC, IOP 10 mm Hg after carbon dioxide laser NPGS on a patient with baseline IOP 26 mm Hg with POAG

Figure 4

Figure 3

Figure 2

Figure 1

Manish Panday, Ronnie George - Non Penetrating Glaucoma Filtering Surgery

323

MajorReviewSelective Laser Trabeculoplasty

Address for Correspondance: Smt. Jadhavbai Nathmal Singhvee Glaucoma Services, Sankara Nethralaya, 18, College Road, Chennai

G Balu, DNB, Ronnie George, MS

Laser trabeculoplasy has been used to lower the intraocular pressure for more than four decades. Various lasers have been most commonly the Argon laser, Diode laser and continuous frequency doubled ND: YAG laser.

The exact mechanism of how Laser trabeculoplasty acts to reduce IOP is not well understood. Theories include a mechanical effect, a biochemical effect, and a cellular effect. In a recent review Stein and Challa noted that since both lasers have similar IOP reducing effects and safety profile it was likely that both act by the same mechanism.1 With this background it is reasonable to conclude that the tissue damage occurring with ALT (disruption and coagulation damage to the trabecular tissue and membrane growth over the trabecular meshwork) is not required for the hypotensive effect. The SLT is based on the concept of selective photothermolysis. This results in targeted thermally mediated radiation damage to a selected pigmented cell population within a tissue of mixed cell types of differing pigmentation. Typically the SLT delivers a 400 mm diameter treatment spot ( energy 0.4-1.2mJ per spot) in 3 nanoseconds. This results in energy fluence levels to the TM that are several thousand times lower than with ALT. In the trabecular meshwork this acts upon only pigmented trabecular meshwork cells which absorb the laser energy selectively, sparing damage to surrounding tissue. Histo-pathological studies in human eyes have shown intact trabecular beams with absence of coagulative damage. Continuous endothelial lining was found while pigmented trabecular cells showed disrupted pigment granules. The similarity in ocular hypotensdive response without the attendant tissue damage have resulted in a recent resurgence in interest in laser trabeculoplasty. Latina et al were the first to publish efficacy data for the SLT.2 In a prospective,

nonrandomized clinical trial in OAG uncontrolled on medical therapy with prior ALT treatment. Fifty three eyes (One eye per subject) received 180 degrees SLT, and both eyes continued their pretreatment medical therapy postoperatively. Mean IOP reduction in SLT-treated eyes was 6.0mm Hg (P<0.001) in eyes previously treated with ALT and 5.8mm Hg (P<0.001) in eyes without prior ALT treatment. Overall, 70% of eyes exhibited an IOP reduction of at least 3mm Hg.

Comparison between ALT and SLT

Numerous studies show equal efficacy of both the treatments irrespective of previous ALT treatments.3,4 The Glaucoma

Laser Trial reported that after ALT only 32% of eyes were still controlled with no additional IOP-lowering demonstrated that by 5 years. Both also appear to have similar duration of action, with both techniques losing efficacy over time. Juzych et al performed a retrospective comparison of SLT and ALT, they reported reported success rates (20% or greater IOP reduction without further intervention) in eyes with medically uncontrolled OAG at 1, 3, and 5 years of 58% to 68%, 38% to 46%, and 31% to 32%, respectively, for SLT and 46% to 54%, 23% to 30%, and 13% to 31%, respectively, for ALT. 5

How much to treat : There is some evidence to suggest that treatiung a greater part of the angle is likely to result in more IOP reduction. Nagar et al reported that 90 degrees SLT treatment produced lower success rates than either 180 or 360 degrees SLT. While 360 degree treatment appeared to be more effective than 180 degree treatment this did not reach statistical significance. Larger treatment (360 degrees compared to 90 degrees) was associated with greater ocular pain, however IOP spikes and anterior chamber inflammation were similar.

Repeat treatments: There are numerous reports comparing effect of SLT after ALT. There are fewer reports on the efficacy of repeat SLT. In a retrospective case series of eyes undergoing a repeat 360 degree SLT after loss of IOP control following the first treatment Hong et al found that IOP’s did reduce though somewhat less than with the first treatment. Percentage of eyes achieving a 20% or greater IOP reduction within the first month post treatment, at 1-3 month post treatment and at 5-8 months post treatment were 29.5%, 54.5% and 50% respectively following the first treatment and 40.5%, 36.5% and 43.2% respectively after the repeat treatment.

Procedure

Laser Parameters: SLT delivers laser energy using Q-switched ND: YAG laser 0.8 to 1.6 mJ , spot size 400 micro meters. A Goldmann 3 mirror contact lens or the Latina laser lens is used with a coupling medium such as methyl cellulose and placed over the eye .The laser is aimed at pigmented trabecular meshwork.50 non overlapping spots are placed. There is no visible end point but some authors increase the energy till small champagne bubbles are visualised. Pre- treatment with apraclonidine eye drops or systemic acetazolamide should be considered to blunt a post laser IOP spike.


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Post procedure topical steroids or NSAIDS and anti glaucoma medications are continued for 4 weeks.

The ocular hypotensive effect usually is first is seen after a week and a small additional benefit after 4-6 weeks.

Indications: Uncontrolled Ocular hypertension, POAG, pigmentary glaucoma, pseudo exfoliative glaucoma, Poor compliance with medical therapy , intolerance or non response to medical therapy

Contra indications: iritis , uveitis and closed angle

Adverse effects

Transient IOP elevation. Pain, discomfort and redness, Peripheral anterior synecheiae. Anterior chamber inflammation. In pigmentary glaucoma Van de Veire et al reported a paradoxical IOP rise following SLT of nearly 20% that persisted for 12 weeks. In another case series Harasymowycz IOP spikes in 4 patients with heavily pigmented angles, with peak IOP’s ranging from 31 to 65mm Hg, three of them required filtering surgery.

While the SLT is a useful addendum to the glaucoma armamentarium, there is little data on its efficacy or cost

effectiveness in Indian eyes. One should keep in mind that IOP reductions are typically modest and do not last for long periods. Patients treated with SLT will need to be on close follow up even post treatment. Care should be taken in eyes with a densely pigmented trabecular meshwork.

References1. Stein JD, Challa P.Mechanisms of action and efficacy of argon laser trabeculoplasty and selective laser trabeculoplasty. Curr Opin Ophthalmol. 2007; 18(2):140-52. Latina MA, de Leon JM. Selective laser trabeculoplasty.Ophthalmol Clin North Am. 2005 ;18(3):409-193. Damji KF, Bovell AM, Hodge WG, Rock W, Shah K, Buhrmann R, Pan YI. Selective laser trabeculoplasty versus argon laser trabeculoplasty: results from a 1-year randomised clinical trial. Br J Ophthalmol. 2006 ;90(12):1490-4. 4. Birt CM. Selective laser trabeculoplasty retreatment after prior argon laser trabeculoplasty: 1-year results. Can J Ophthalmol. 2007 Oct;42(5):715-95. Juzych MS, Chopra V, Banitt MR, Hughes BA, Kim C, Goulas MT, Shin DH. Comparison of long-term outcomes of selective laser trabeculoplasty versus argon laser trabeculoplasty in open-angle glaucoma. Ophthalmology. 2004 ;111(10):1853-9.

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MajorReview

Challenges in the Management of Glaucoma coexistent with Cataract

Gowri J Murthy, DNB, FRCO (Lon), FRCS (Edin)

Address for Correspondance: Dr.Gowri J Murthy, Vittala International Institute of Ophthalmology, CA site no1, 2 cross, 2 main, BSK 3rd stage, Bangalore 560085

Glaucoma and cataract are both well recognized causes of preventable and curable blindness respectively. A general ophthalmologist, very often encounters situations where the two coexist. Despite extensive literature published on this subject, lot of gray areas and unanswered questions abound, about the combined management of cataract and glaucoma. There are no formula based or rule of thumb approaches. Knowledge of management nuances and tailoring one’s approach to a situation can help management of these problems, when coexistent.

Evaluation of a patient with both cataract and glaucoma

The key to effective management lies in appropriate and comprehensive evaluation of the patient, pre operatively. Failing to diagnose glaucoma, in a patient with cataract can spring unwelcome surprises in the post operative period, and prove disappointing, both to the surgeon, as well as the patient.

Evaluation of the cataract

Type and location of lens opacity

As in the routine evaluation of any patient with cataract, the type of cataract, and its location should be evaluated pre operatively. Certain types of localized posterior sub capsular cataracts can give rise to localized defects on visual fields, which can mimic glaucomatous defects.

Pupil dilation and other pupil related issues

Pupil related issues often coexist with glaucoma, and are very relevant when planning cataract surgery. Pre operatively, it helps to assess the extent of pupil dilation. Posterior synechiae may be present, due to previous use of pilocarpine, or inflammation. Inadequate pupil dilation may necessitate the usage of pupil stretching techniques, iris hooks, or pupil expanders.1

Use of these techniques invariably results in more pigment dispersion in the AC, multiple clear corneal/ limbal incisions, more inflammation than usual post operatively, and can have an effect on the post operative outcome of a combined trabeculectomy. Loss of sphincter tone can leave the iris floppy, and post operatively predispose to peripheral anterior synechiae, and posterior synechiae formation.

It would also be prudent to stop pilocarpine pre operatively if it is being used, as usage of pilocarpine , in addition to its

miotic effect, can affect the blood ocular barrier and lead to more severe and prolonged post op inflammation.

Zonular integrity

An assessment of the zonular integrity pre operatively, after dilating the pupil is mandatory in all eyes with glaucoma and cataract. Pseudo exfoliation and coexisting zonular weakness can be easily missed if slit lamp examination is not done with dilated pupil.2 In the presence of weak zonules one should have a plan to deal with it, by the use of endocapsular rings, or segments. Possibility of having to make additional conjunctival incisions and scleral flaps, for fixation of capsule tension rings, and scleral fixated intraocular lenses should be kept in mind.

Pseudo exfoliation: Presence of typical powdery pseudoexfoliative material on the pupil edge and lens capsule aid in the diagnosis. Examination of the eye after dilation is mandatory, as sometimes PXS can be missed in the undilated state. The implications for cataract management include non dilating pupils, and zonular instability. The glaucoma associated with PXS can have more IOP fluctuation, and also progress at a faster rate compared to POAG, and has to be managed appropriately. Post cataract surgery, capsular phimosis, and contracture occur in a slightly higher rate than expected. For this reason silicone foldable lenses are not recommended in eyes with pseudoexfoliation.2 There is also a recommendation to consider cataract surgery early in such eyes, as surgery in the presence of very dense nuclear sclerosis, and zonular instability very frequently tends to become complicated.2

Anterior chamber depth, presence of issues like relative anterior microphthalmos/ nanophthalmos

Many eyes with angle closure glaucoma also have shallow anterior chambers and this is a factor which has to be taken into consideration when planning cataract surgery. Use of highly retentive viscoelastics like Healon-5TM may help anterior chamber maneuvers in the presence of a very shallow AC

Relative Anterior Microphthalmos ( RAM) 3: This is a clinical entity characterized by horizontal corneal diameter < 11mm, Axial length >/= 20 mm, with no visible malformation in the anterior chamber. These eyes have normal axial length, but a disproportionately small anterior chamber. Clinically RAM patients have a high incidence of glaucoma, (77%) and also may have associated guttate changes in the corneal


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endothelium, as well as Pseudo exfoliation and poorly dilating pupils. Combinations of such factors make cataract surgery in such eyes very challenging.

Cilio lenticular block post operatively is also more common in such eyes. Proper pre operative evaluation and identification of such eyes can help us plan cataract surgery and minimize complications.3 IOL power calculation in short eyes and in eyes with RAM, is better done with formulae designed for the same- e.g. Haigis, Holladay II formulae for high hypermetropia, and nanophthalmos. Higher IOL powers may sometimes be required and necessitate piggy back IOLs. 4

Nanophthalmos is a well recognized clinical entity. The corneal diameter ranges from 9-11mm, total axial length in the range of 14- 17 mm (less than 20 mm). Patients typically have high hypermetropia, and an abnormally thick sclera. One can also describe such eyes as having a “normal” sized lens in a small eye. Cataract Surgery, in addition to being technically challenging in such eyes, is complicated by serous retinal detachments, and choroidal detachments, post operatively. Dissection of partial thickness scleral windows near the vortex veins helps in preventing development of such effusions. Proper pre operative evaluation can help detection of this condition pre operatively, and planning the surgery can help us achieve good results.5, 6

Evaluation of GlaucomaPreoperative assessment of Glaucoma, and the extent of disc and fields damage, is central to the management of a patient with both cataract and glaucoma.

IOP and target IOP

The highest untreated IOP at which glaucoma damage occurred and the estimated target IOP should be known for all patients pre operatively. The number of antiglaucoma medications required to keep the IOP at target should also be factored, in the decision making process. If IOPs are well controlled with a single antiglaucoma medication, in the presence of mild to moderate disc and fields’ damage, cataract surgery alone may be considered. Use of multiple medication to achieve target IOP, and IOPs higher than target despite maximal medications will necessitate a combined trabeculectomy with cataract surgery. In the presence of very advanced glaucoma with threatened or split fixation, and IOPs not under control with maximal antiglaucoma medications, it may even be an option to just perform a trabeculectomy with antimetabolite, allow for control of IOPs and establishment of a good filtering bleb, and plan cataract surgery after 3-6 months.

Fields

Visual fields evaluation is a must ,by any standard threshold perimetry, pre operatively. Documenting the visual fields

status pre operatively helps in preventing post operative surprises due to extensive glaucomatous disc damage. It is also a tool to counsel the patient regarding the extent of visual recovery to expect following removal of the cataract.

Visual fields helps us determine the extent of visual field loss due to cataract as compared to that from glaucoma damage. The total deviation probability plot usually can be correlated to the extent of cataract, and the pattern deviation plot, the extent of glaucoma damage. In very advanced glaucoma’s the glaucomatous loss itself is very extensive, and generalized. In such situations, the pattern deviation plot becomes meaningless. In such eyes using central fields testing by programmes like 10-2/ macular programmes can help prognosticate the extent of visual recovery.

ONH- clinical evaluation, relevance and utility of imaging techniques:

A dilated stereoscopic assessment of the optic nerve head is mandatory in all eyes pre operatively. One must remember that in eyes with very dense nuclear sclerosis, the disc gets a pink/ reddish hue as a result of the dense nuclear sclerosis, and one must not use pallor to differentiate from cup and rim, while evaluating the optic nerve head. Contour clues to determine the extent of cupping are more accurate. Even a 0.9 cupped disc may misleadingly appear pink in such eyes, leading to underestimation of glaucoma damage. Disc findings must be correlated with the visual fields, to determine extent of glaucomatous damage.

There has been an emergence of imaging technologies which are useful in documenting and determining extent of structural loss. Most of these technologies however have limitations in the presence of a significant cataract. Poor quality images and falsely low RNFL thickness values are frequently encountered. Acquiring RNFL analysis/ ONH analysis images after pupil dilation can sometimes overcome errors due to minimal lens opacities.

Angle

Pre operative Gonioscopy is also mandatory, to differentiate between open and closed angles in a newly diagnosed case. Presence of synechiae may have to be considered in planning incision sites for cataract and trabeculectomy.

Type of glaucoma and its relevance to formulating the management plan

There is an ongoing debate about cataract extraction alone, in the management of angle closure glaucoma. The hypothesis proposed is that the removal of the lens widens the angle, and can help contribute towards control of IOPs without need for additional glaucoma surgery. Evidence in literature today is definitely not conclusive in this regard. There is some evidence that the amount of IOP reduction

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Gowri J Murthy - Glaucoma and Cataract

with cataract extraction alone may be higher in ACG eyes in comparison to OAG eyes. However whether this amount of IOP reduction is enough in a particular patient is something that has to be answered on an individual basis. In presence of moderate to advanced glaucoma damage, and use of multiple medications for control of IOP, it may be prudent to plan a combined surgery, rather than err on the side of cataract surgery alone.

Formulation of Management plan Combined surgery, or cataract surgery alone?

There are many unanswered questions in the management of glaucoma combined with cataract. Conflicting reports in literature do exist. There is no consensus among glaucoma specialists as to when to recommend glaucoma surgery alone, and when to recommend a combined surgery.

A systematic review of literature commissioned by the American Academy of Ophthalmology, to answer these questions was published in Ophthalmology by Friedman et al.7

The findings of this systematic review are as follows.

Cataract surgery alone and long term IOP control: Evidence was consistent that cataract extraction alone (both Phaco ECE and ECCE) decreased the IOP of glaucoma patients by an average of 2 to 4 mmHg at 1 to 2 years after surgery.

Combined surgery and long term IOP control: There is weak evidence that (1) PECE plus trabeculectomy decreased IOP by approximately 8 mmHg in individuals followed up for 1 to 2 years, and (2) ECCE and trabeculectomy combined decreased IOP by 6 to 8 mmHg in subjects followed up for 1 to 2 years.

There is strong evidence that long-term IOP control is significantly better with combined glaucoma and cataract procedures (PECE and ECCE) than with cataract extraction alone.

There is weak evidence that trabeculectomy alone lowers long-term IOP slightly more than combined PECE and trabeculectomy and trabeculectomy alone lowers long-term IOP more than combined ECCE and trabeculectomy.

The data are inconclusive as to whether cataract extraction negatively impacts pre-existing filtering blebs.7

Technique of combined surgery, and the use of antimetabolites

There is no consensus on recommended technique, and superiority of single site v/s two site approaches, when performing combined surgeries. A systematic review of literature to address this question, has been published by Jampel et al.8

The findings of this systematic review are:8

There is moderate evidence that use of Mitomycin C results in lower IOPs ( 2-4 mmhg lower) when combined surgeries are performed , in comparison to not using an antimetabolite.

There is no evidence that 5FU offers significant advantages in IOP control over not using an antimetabolite during combined surgery

There is moderate evidence that two site surgery results in slightly lower IOPs ( by 1- 2 mmhg) compared to single site surgery.

There is weak evidence that phacoemulsification as the technique of cataract surgery , in combined surgery, is better and lowers IOP by 1-2 mmhg more, compared to lens expression techniques( non Phaco surgeries)

There was insufficient evidence that staged / sequential trab followed by Phaco surgeries offer better control, in comparison to combined surgical approaches.

There was insufficient evidence to evaluate the efficacy of alternate glaucoma surgeries ( e.g. cyclodestruction, implants) in conjunction with cataract surgery.8

Surgical techniqueSpecial aspects to glaucoma surgery, when combined

Conjunctival flap: a fornix based flap may be preferred due to better visualization when combined surgeries are done regardless of single site or two site approaches. Closure of the conjunctival flap should be meticulous with mattress sutures at the limbus to avoid post operative bleb leaks.

Special aspects to cataract surgery

Technique- Phaco/ non Phaco- As earlier mentioned, due to the clear corneal approach, and smaller size, phacoemulsification may be the better technique of cataract surgery in combined surgeries.

Incision site: Temporal clear corneal Phaco approach has been recommended, with superiorly situated trabeculectomy, by many surgeons. Some however perform phacoemulsification through superior temporal, and trabeculectomy through superonasal sites or vice versa. There is no evidence regarding the superiority of either technique. 8

IOL selection: Foldable lenses offer advantages due to smaller cataract incision sizes. There is insufficient evidence in literature regarding the use of multifocals in a patient with glaucoma. Multifocals may influence visual fields results, and imaging techniques to estimate glaucoma damage may not be accurate in the presence of multifocals.


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Pupil management: Small pupil can be managed with iris hooks or pupil expanding rings.

Zonule management: endocapsular rings/ segments can be used if zonular insufficiency is suspected.

Mid course corrections - what to do in case of complications?

Vitreous loss in combined surgery: If vitreous loss occurs during combined surgery, a thorough automated anterior vitrectomy must be done. Care should be taken that the internal ostium is not blocked by formed vitreous. Intracameral tricort can be used to delineate the vitreous and aid in complete anterior vitrectomy. However one should monitor IOPs closely, in the post operative period due to risk of steroid response.

Preexisting glaucoma with cataract

Cataract surgery in an eye status post trabeculectomy

A temporal clear corneal approach to cataract surgery is preferred in the presence of a functioning filtering bleb superiorly.

There are some reports in literature that the functioning of a filtering bleb decreases following subsequent cataract surgery.

Post operative management IOP monitoring post surgery : Post operative management is very important in the case of combined surgery. These patients should be monitored, with more frequent post operative visits and IOP should be monitored at each visit. The frequency of visits can be determined based on the post operative bleb functioning and IOP.

Steroid responders : The incidence of steroid response if patients with glaucoma is higher compared to the general population. Therefore close IOP monitoring is mandatory. Raised IOP in the presence of a functioning filtering bleb may indicate contribution of steroid induced IOP response, and in such cases switching to a lower potency steroid like dexamethasone, or fluoromethalone may lower the IOP.

Aggressively Healing bleb post combined surgery: Aggressive healing of the bleb can contribute to failure of trabeculectomy between the first and third weeks after surgery. After the second week, the cataract incision usually would have healed, and digital massage can be advised, albeit with caution. Post operative 5 FU injections can also be used, and releasables if in place can be released. Laser suture lysis can also be considered.

Establishing the new baseline- Implications for

long term management of Glaucoma: Lastly one should establish a new baseline after cataract surgery to aid the continued management of glaucoma. This requires visual fields and optic nerve imaging studies to be repeated after cataract surgery to document the new baseline. One should ensure that the patient understands that Glaucoma needs continued follow up, even after combined surgery.

A meticulous approach with through pre op evaluation, having an operative plan, and closely following up patients post operatively , can help in effective management of the combined problems of glaucoma and cataract.

References

1) Ahmet Akman, Gürsel Yilmaz, Sibel Oto, Yonca Aydin

Akova, Comparison of various pupil dilatation methods for

phacoemulsification in eyes with a small pupil secondary to

pseudoexfoliation ,Ophthalmology. 2004: 111; 1693-1698

2) Gottfried O.H Naumann, Ursula Schlötzer-Schrehardt, Michael

Küchle Pseudoexfoliation syndrome for the comprehensive

ophthalmologist: Intraocular and systemic manifestations

,Ophthalmology .1998:6;951-968

3) Gerd U Auffarth, Markus Blum, Ute Faller, Manfred R Tetz, Hans E

Völcker Relative anterior microphthalmos Morphometric analysis and

its implications for cataract surgery Ophthalmology.2000:8;1555-1560.

4) Edward J. Wladis, Matthew B. Gewirtz, Suqin Guo Cataract

Surgery in the Small Adult Eye. Surv. Ophthalmol. 2006:2;153-161

5) Wayne Wu, Daniel G Dawson, Alan Sugar, Susan G Elner, Kathy

A Meyer, Jesse B McKey, Sayoko E Moroi,Cataract surgery in patients

with nanophthalmos: Results and complications. Journal of Cataract

& Refractive Surgery. 2004 :3; 584-590

6) Masanobu Uyama, Kanji Takahashi, Jun Kozaki, Nobuko Tagami,

Yuriko Takada, Hiroshi Ohkuma, Hiroshi Matsunaga, Takashi Kimoto,

Tetsuya Nishimura Uveal effusion syndrome1 Clinical features,

surgical treatment, histologic examination of the sclera, and

pathophysiology Ophthalmology, 2000:3; 441-449

7) David S Friedman, Henry D Jampel, Lisa H Lubomski, John H

Kempen, Harry Quigley, Nathan Congdon, Hani Levkovitch-Verbin,

Karen A Robinson, Eric B Bass Surgical strategies for coexisting

glaucoma and cataract: An evidence-based update,Ophthalmology

2002:10;1902-1913

8) Henry D Jampel, David S Friedman, Lisa H Lubomski, John H

Kempen, Harry Quigley, Nathan Congdon, Hani Levkovitch-Verbin,

Karen A Robinson, Eric B Bass Effect of technique on intraocular

pressure after combined cataract and glaucoma surgery: An

evidence-based review Ophthalmology 2002:12;2215-2224

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Fig 1: Flow chart for management of Cataract and Glaucoma

Gowri J Murthy - Glaucoma and Cataract

330

MajorReview

Pseudo Exfoliation Syndrome : An identifiable cause of Open Angle Glaucoma

Savita Bhat MS

Address for Correspondance: Giridhar Eye Institute, Cochin 682 020

Introduction

Pseudo exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of an abnormal fibrillar extracellular material in many ocular tissues and is the most common identifiable cause of open-angle glaucoma worldwide. Exfoliation syndrome plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract, and retinal vein occlusion. Glaucoma occurs more commonly in eyes with XFS than in those without it; in fact, XFS has recently been recognized as the most common identifiable cause of glaucoma. Patients with XFS are also predisposed to develop angle-closure glaucoma, and glaucoma in XFS has a more serious clinical course and worse prognosis than primary open-angle glaucoma.

History

In 1917, a Finnish ophthalmologist named Lindberg first described pseudo exfoliation syndrome. This entity is characterized by flakes of granular material at the pupillary margin of the iris and throughout the inner surface of the anterior chamber. It is also associated with secondary open-angle glaucoma, known as pseudo exfoliation glaucoma, which is the most common identifiable form of secondary open-angle glaucoma worldwide. Dvorak-Thebold suggested the term pseudo exfoliation to differentiate it from true exfoliation or lamellar delamination of the lens capsule found in glassblowers. True exfoliation syndrome is due to heat or infrared-related changes in the anterior lens capsule.

Pathophysiology

Pseudo exfoliation syndrome is a common ocular manifestation of a systemic disease, known to cause disease primarily in the eye. Exact etiology of this condition remains unknown. . Exfoliation syndrome appears to be a disease of elastic tissue microfibrils. Despite extensive research, the exact chemical composition of exfoliation material (XFM) remains unknown. An overproduction and abnormal metabolism of glycosaminoglycans have been suggested as one of the key changes in XFS. The protein components of XFM include both noncollagenous basement membrane components and epitopes of the elastic fiber system such as fibrillium. Regardless of etiology, typical exfoliation fibers have been demonstrated electron microscopically in close association with the pre-equatorial lens epithelium, the nonpigmented ciliary epithelium, the iris pigment epithelium, the corneal endothelium, the trabecular endothelium, and with almost all cell types of the iris stroma, such as fibrocytes, melanocytes,

vascular endothelial cells, pericytes, and smooth muscle cells.

Pseudo exfoliation material is associated with abnormalities of the basement membrane in epithelial cells and has a wide distribution throughout the body. Pseudo exfoliative material has been found in the walls of the vortex veins and the central retinal artery. Extraocular tissues involved include lung, skin, liver, heart, kidney, gallbladder, blood vessels, extraocular muscle, connective tissue in the orbit, and meninges. In the anterior segment of the eye, it is characterized by deposition of pseudo exfoliative amyloid like material on the anterior lens capsule, ciliary body, zonules, pupillary margin of the iris, corneal endothelium, anterior vitreous, and trabecular meshwork.

Some investigators believe that the iris pigment epithelium, the ciliary epithelium, and the peripheral anterior lens epithelium produce this pseudo exfoliative amyloidlike material, which moves into the aqueous humor and is carried to the trabecular meshwork, following the normal flow. Obstruction of the trabecular meshwork by this fibrillar material and pigment associated with degenerative changes in the Schlemm canal and the juxtacanalicular area causes elevation of the intraocular pressure (IOP) with associated glaucoma.

Zenkel et al have studied genes differentially expressed in anterior segment tissues and have postulated that pseudo exfoliation syndrome is a stress-induced elastic microfibrillopathy.1

FrequencyRegional

In Asia, the prevalence in a Japanese population was 3.4%. Hospital-based studies showed a prevalence of 6.45% in Pakistan and 7.4% in India. A prevalence rate of 0.4% in patients aged 60 years or older was identified in China.

International

Roth and Epstein reported that pseudo exfoliation glaucoma was present in 12% of patients with glaucoma.2

In the Framingham study, prevalence of pseudo exfoliation syndrome was 1.8%. In a prospective study, Cashwell and Shields found that the prevalence of pseudo exfoliation syndrome in the south eastern United States was 1.6% of the total population and in 6% of an open-angle glaucoma subpopulation.3 Because of the increased mean age of populations, pseudo exfoliation syndrome may become more prevalent in the future. Prevalence of pseudo exfoliation

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syndrome in Europe was found to be 4.7% in England, 6.3% in Norway, 4% in Germany, 1.1% in Greece, and 5.5% in France.

Bartholomew reported an 8.2% prevalence of pseudo exfoliation syndrome in the Bantu tribes of South Africa.4

Race

Although it occurs in virtually every area of the world, a considerable racial variation exists in the incidence of pseudo exfoliation glaucoma. In Scandinavian countries, more than 50% of cases of open-angle glaucoma are caused by pseudo exfoliation syndrome. Pseudo exfoliation syndrome is relatively rare among African Americans and Eskimos. It was not observed at all in the Inuit who live throughout the Canadian Arctic. Prevalence is high in the Sami people who are indigenous of northern Europe. Among the Bantu tribes of South Africa, exfoliation was found in 19% of patients in a glaucoma clinic. In Saudi Arabia, Summanen and Tonjum reported a prevalence of pseudo exfoliation syndrome of 13%. Prevalence of pseudo exfoliation syndrome in Spanish Americans in New Mexico was estimated to be 3-6%.

Mortality/Morbidity

In a retrospective study, Shrum et al found no association between ocular pseudo exfoliation and cardiovascular or cerebrovascular mortality.5 However, other authors have found that pseudo exfoliation is linked with Alzheimer disease, senile dementia, cerebral atrophy, chronic cerebral ischemia, stroke, transient ischemic attacks, heart disease, and hearing loss. Vessani et al found that homocysteine levels were higher among patients with pseudo exfoliation syndrome and pseudo exfoliative glaucoma compared with controls.6 Roedl et al reported increased homocysteine concentrations in tear fluid and plasma of patients with pseudo exfoliation glaucoma.7 Elevated plasma homocysteine levels have been described as a risk factor for cardiovascular disease.

Sex

Pseudo exfoliation syndrome is more common in females than in males. In a series by Kozart and Yanoff, pseudo exfoliation syndrome was 3 times more common in women than in men.8

Age

Pseudo exfoliation syndrome is rarely seen before age 50 years, and its incidence increases steadily with age.

Clinical Evaluation

History

Patients may be asymptomatic, or they may complain of decreased visual acuity secondary to cataract or glaucomatous visual field changes.

Physical

Pseudo exfoliation syndrome is diagnosed clinically by slit lamp examination with an 85% sensitivity rate and a 100% specificity rate.

• Pseudo exfoliative material can be seen on the pupillary border of the iris without dilation. Pseudo exfoliative material is seen in the image below.

• The most commonly recognized feature is the 3-ring sign on the anterior lens capsule, formed by a central disc, a peripheral ring, and a clear zone, which separates the two. The clear zone varies in diameter and may exhibit curled edges.

• The central disc measures 1-2.5 mm in diameter and has well-demarcated borders.

• The peripheral ring typically is seen after pupillary dilation. Its size is variable, and its inner border has many radial striations.

Figure 1 - Pseudoexfoliation on lens capsule

• The translucent zone most likely is created by the physiologic rubbing of the posterior surface of the iris against the lens. It scrapes the pseudo exfoliative material from the surface of the lens. This scraping results in a secondary pigmentary dispersion syndrome, with a loss of melanin from the iris pigment epithelium at the pupillary margin adopting a sawtooth-like morphology. Accumulation of melanin granules in the trabecular meshwork ensues. Peripupillary iris atrophy is a common and distinctive finding. It is best visualized using infrared transillumination.

• Gonioscopy shows a discontinuous pigmentation of the trabecular meshwork, usually less dense than seen in pigmentary glaucoma. Also, pigment characteristically is deposited on the Schwalbe line or anterior to the Schwalbe line (the Sampaolesi line). A high incidence of narrow, or occludable, angles in eyes with pseudo exfoliation has been reported.

Savitha Bhat - Pseudo exfoliation syndrome


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• Elevated IOP leads to glaucoma development in about 50% of patients. Puska et al reported that the conversion rate from pseudo exfoliation syndrome to pseudo exfoliation glaucoma was 3.2% per year.9 Jeng et al found that, in patients with pseudo exfoliation, the probability of developing glaucoma was 44% after 15 years, and, in a study by Grodum et al, 55.1% of patients developed glaucoma after a mean of 8.7 years.10,11

• When glaucoma develops, it is frequently referred to as capsular glaucoma. Patients with pseudo exfoliation syndrome have higher IOP than patients with primary open-angle glaucoma. Because of these higher IOPs, visual field loss and optic nerve damage are more pronounced.

• Other signs of pseudo exfoliation syndrome are insufficient mydriasis, posterior synechiae, pigment deposition on the iris surface, deposition of pigment and pseudo exfoliation material on the corneal endothelium, pigment liberation after pupillary dilation, and pseudo exfoliation material covering the ciliary processes and the zonules. Phacodonesis, lens subluxation, and corneal endothelial decompensation can be present. An associated nuclear cataract is a common finding.

• Pseudo exfoliation syndrome typically presents unilaterally. Why this occurs remains unknown. The fellow eye develops signs of pseudo exfoliation in more than 40% of cases, but pseudo exfoliation material can almost always be demonstrated in fellow eyes on electron microscopy and conjunctival biopsy.

• Pseudo exfoliation syndrome is associated with reduced ocular blood flow, iris hypoperfusion, and anterior chamber hypoxia.

• Oxidative damage and free radicals may play a role in the disease. A decrease in ascorbic acid concentrations,12

increased 8-iso-prostaglandinF2a concentrations,13 and increased malondialdehyde concentrations14 have been reported.

Causes

Whether pseudo exfoliation syndrome occurs as part of a genetic process or in association with other diseases is not clear. Familial aggregation supports the notion that it may be inherited as an autosomal dominant trait with incomplete penetrance and late onset. Its frequency increases with age; however, it is not part of normal aging. Possible predisposing factors include ultraviolet light, northern latitudes, and altitude. Climate factors may not play a definitive role in the pathogenesis of the disease.

The exact nature of pseudo exfoliation material remains unknown, although its close association with zonular fibers supports the idea of pseudo exfoliation syndrome as a type of

elastosis, affecting elastic microfibrils. It seems to arise from abnormal aggregation of elastin microfibrillar components.

• In 2007, Thorleifsson et al studied Icelandic and Swedish patients with glaucoma. They found that 2 nonsynonymous single-nucleotide polymorphisms (SNPs) (rs1048661, R141L; rs3825942, G153D) in exon 1 of the lysyl oxidase-like protein 1 gene (LOXL1) represent a major susceptibility variant for pseudo exfoliation syndrome and support the idea that the variant confers risk of glaucoma by causing pseudo exfoliation syndrome. These findings have been corroborated by Fingert et al in the United States.15 By fluorescence in situ hybridization, Kenyon et al mapped the human LOXL gene to 15q24-q25.16

• The risk of pseudo exfoliation glaucoma is 700 times in individuals homozygous for the high-risk haplotypes. The 2 non-synonymous changes are highly associated with pseudo exfoliation syndrome and account for more than 99% of all pseudo exfoliation glaucoma cases from Iceland and Sweden and 88% of cases in Iowa. Fan et al found a strong association between non-synonymous single-nucleotide polymorphisms G152D, but not R141L, and pseudo exfoliation in a clinic-based population from the Northeastern United States.

• The LOXL1 gene has been associated with the lysyl oxidase family of proteins that has important roles in elastogenesis. LOXL1 pro-peptide binds to both tropoelastin and fibulin-5 and alterations of the gene could affect the catalytic activity of the protein producing modifications in the elastin fibers, a major pathophysiological component of the syndrome. LOXL1 serves as a cross-linking enzyme and to ensure proper spatial deposition of elastin.

• The high-risk haplotype of LOXL1 alleles is very common in Caucasians with a frequency of approximately 50% in the general population, 25% being homozygous for the haplotype. This indicates that, even though LOXL1 represents a significant risk factor for pseudo exfoliation, most persons with high-risk LOXL1 alleles do not have the condition. Therefore, other factors that remain to be identified must be involved.

• This finding in 2007 that two common single nucleotide polymorphisms in the coding region of the lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically associated with XFS and XFG should help in planning therapy. LOXL1 is a member of the lysyl oxidase family of enzymes, which are essential for the formation, stabilization, maintenance, and remodelling of elastic fibers and prevent age-related loss of elasticity of tissues. LOXL1 protein is a major component of exfoliation deposits and appears to play a role in its accumulation and in concomitant elastotic processes in intra- and extraocular tissues of XFS patients. This discovery should open the way to new approaches and directions of therapy for this protean disorder.

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• Glaucoma is a secondary event. Blockage of the trabecular spaces by pseudo exfoliation material promotes accumulation of pigment and cellular debris, which causes obstruction of the aqueous channels and limits access to the Schlemm canal. Accumulation of pseudo exfoliation material in the juxtacanicular tissue adjacent to the Schlemm canal leads to narrowing of the canal lumen, collapse of its walls, disruption of its endothelium, and partial obliteration. These changes appear to be the causative factors for chronic IOP elevation and pseudo exfoliation glaucoma.

• Zonular laxity allows forward movement of the lens, causing decreased anterior chamber depth and pupillary or angle closure glaucoma.

• Pseudo exfoliation syndrome itself does not produce optic nerve damage.

Imaging Studies

Various imaging technologies are being used to document and monitor changes due to glaucomatous damage in the optic disc and the retinal nerve fiber layer. These imaging techniques are similar to that in open angle glaucoma.

Optical coherence tomography (OCT) is a valuable tool in the evaluation of glaucoma. OCT provides a cross-sectional view of the scanned retinal area that allows differentiation between the retinal layers. The thickness of the retinal nerve fiber layer can be measured using this technique. The confocal scanning laser ophthalmoscope (Heidelberg retina tomograph [HRT]) provides topographical measures of the optic disc as well as indirect measurements of the retinal nerve fiber layer thickness.OCT and HRT have been used to help in the diagnosis and follow-up of patients with glaucoma. Both OCT and HRT have shown a high correlation between the retinal nerve fiber layer thickness and the visual field mean defect during achromatic perimetry. The GDx Nerve Fiber Analyzer has been reported to be a valuable tool in helping the clinician to discriminate between healthy eyes and glaucomatous eyes. Gonioscopy and visual field testing

Histologic Findings

Gottanka et al found marked differences in the optic nerve between primary open-angle glaucoma and pseudo exfoliation glaucoma.17 Eyes with primary open-angle glaucoma were found to have axon loss associated with more connective tissue in the septa and surrounding the central retinal vessels and a decrease in the density of capillaries as compared with eyes with pseudo exfoliation glaucoma where the capillary density did not change with axon loss.

Medical Care

• Patients with pseudo exfoliation syndrome should have annual eye examinations for early detection of glaucoma. Glaucoma in pseudo exfoliation is more resistant to medical

therapy and has a poorer prognosis than primary open-angle glaucoma.

• The treatment of pseudo-exfoliation glaucoma is the same as that of primary open-angle glaucoma; however, topical medications tend to be less effective. Miotics lower IOP, but they aggravate the blood-aqueous barrier dysfunction and decrease iris mobility, thereby increasing the risk of posterior synechiae and cataract formation.

• Argon laser trabeculoplasty is frequently used with excellent initial success. Its hypotensive effect may be facilitated by enhanced heat absorption because of increased trabecular pigmentation.

• According to a published study, selective laser trabeculoplasty (SLT) has been shown to be equivalent to argon laser trabeculoplasty in terms of lowering IOP at 1 year. The theoretical advantage of SLT is that SLT is a repeatable procedure because it does not seem to produce thermal damage to the trabecular meshwork.

Surgical Care

• If medical therapy and laser therapy are unsuccessful to control the glaucoma, trabeculectomy can be performed with similar success rates to that of primary open-angle glaucoma. Because patients with pseudo exfoliation glaucoma have higher IOP, they tend to undergo glaucoma filtering surgery more frequently than patients with primary open-angle glaucoma.

• Cataracts occur more commonly in patients with pseudo exfoliation syndrome. Weakness of the zonular fibers, spontaneous lens subluxation, and phacodonesis also can be present. Therefore, in these patients, cataract surgery alone or combined cataract surgery and glaucoma filtering surgery in the presence of pseudo exfoliation is associated with a higher incidence of intraoperative complications, most notably zonular dialysis, vitreous loss, and lens dislocation. This occurs 5 times more frequently than in other cases. Naumann 1988, Seorolil 1998 and Shingleton 2006.

• The increased intra-operative posterior capsule complication rate appears to correlate with the level of cataract maturity. Modern surgical techniques involving the use of capsulorrhexis, small-incision surgery, and better viscoelastics have improved the surgical outcome. Capsular tension rings have been used to decrease surgical stress on the zonules. Intraoperative modification to reduce zonular stress should include (a) lower the bottle height for less anterior chamber dynamics and zonular stress. (b) More energy to remove lens and not to move it. Careful performance of I & A steps, newer phaco Ozil, Stellaris and Signature help reduce turbulence within the anterior chamber.



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• Several zonular support devices like iris (Figure 2) refractors and capsule tension ring along with newer OVD’s help in achieving better surgical outcome. Simple standard CTR or modified CTR (Cionis) can be placed (Figure 3). Ahmed CTR can be placed before phaco (Figure 4). Henderson modified CTR can be placed to facilitate cortical cleaning (Figure 5).

Figure 2 - Iris Retractors

Figure 3 - A Simple CTR

Figure 4 - Ahmed CTR

Figure 5 - Henderson’s modified CTR

• Postoperative cataract surgery complications can occur after uneventful operations due to continued destabilization of the zonules and capsular contraction and posterior capsular opacifications. Owing to increase in ageing population, more will have PXF. In PXF, there is likelihood of late in the bag dislocation (Fig. 6).

Figure 6 - Dislocated CTR

Shingleton in 2006 estimated this to be 2 in 100 cases of PXF. Davis et al 2009 quoted 50% of in the bag explants to be due to PXF. In order to prevent in the bag dislocation, the following measures could be resorted to:

(1) CTR – may not prevent dislocation

(2) Early YAG to prevent phimosis (either radially or circumferentially).

(3) Suturing the haptic to the sclera

(4) Placement of lens in the sulcus

• Jacobi et al described a non-filtering surgical technique

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consisting of trabecular aspiration with or without cataract removal with encouraging results. The operation attempts to increase the outflow facility along the trabecular meshwork by removing pretrabecular and trabecular debris using an externally applied suction device.

In summary, XFG does not respond well to anti-glaucoma medications. They tend to progress faster, are more refractory to treatment and often present with co-exisisting lens changes. The presence of XFS should alert the clinician to the increased risks of intraocular surgery, most commonly zonular dehiscence, capsular rupture, and vitreous loss during cataract extraction. Therefore, the decision of cataract or combined surgery should be weighed with caution in these patients. Heightened awareness of this condition and its associated clinical signs are important in the detection and management of glaucoma, and preoperative determination of those patients at increased risk for surgical complications.

References1. Zenkel M, Poschl E, von der Mark K, Hofmann-Rummelt C, Naumann GO, Kruse FE, et al. Differential gene expression in pseudoexfoliation syndrome. Invest Ophthalmol Vis Sci. 2005;46(10):3742-52.2. Roth M, Epstein DL. Exfoliation syndrome. Am J Ophthalmol. 1980;89(4):477-81. 3. Cashwell LF Jr, Shields MB. Exfoliation syndrome in the southeastern United States. Prevalence in open-angle glaucoma and non-glaucoma populations. Acta Ophthalmol Suppl. 1988;184:99-102. 4. Bartholomew RS. Pseudocapsular exfoliation in the Bantu of South Africa. Occurrence and prevalence. Br J Ophthalmol. 1973;57(1):41-5. 5. Shrum KR, Hattenhauer MG, Hodge D. Cardiovascular and cerebrovascular mortality associated with ocular pseudoexfoliation. Am J Ophthalmol. 2000;129(1):83-6. 6. Vessani RM, Ritch R, Liebmann JM, Jofe M. Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol. 2003;136(1):41-6.

7. Roedl JB, Bleich S, Reulbach U, Rejdak R, Kornhuber J, Kruse FE, et al. Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma. J Glaucoma. 2007;16(2):234-9. 8. Kozart DM, Yanoff M. Intraocular pressure status in 100 consecutive patients with exfoliation syndrome. Ophthalmology. 1982;89(3):214-8.9. Puska PM. Unilateral exfoliation syndrome: conversion to bilateral exfoliation and to glaucoma: a prospective 10-year follow-up study. J Glaucoma. 2002;11(6):517-24. 10. Jeng SM, Karger RA, Hodge DO, Burke JP, Johnson DH, Good MS. The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma. 2007;16(1):117-21. 11. Grodum K, Heijl A, Bengtsson B. Risk of glaucoma in ocular hypertension with and without pseudoexfoliation. Ophthalmology. 2005;112(3):386-90. 12. Koliakos GG, Konstas AG, Schlotzer-Schrehardt U, Bufidis T, Georgiadis N, Ringvold A. Ascorbic acid concentration is reduced in the aqueous humor of patients with exfoliation syndrome. Am J Ophthalmol. 2002;134(6):879-83.13. Koliakos GG, Konstas AG, Schlötzer-Schrehardt U, Hollo G, Katsimbris IE, Georgiadis N. 8-Isoprostaglandin F2a and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome. Br J Ophthalmol. 2003;87(3):353-6.14. Yimaz A, Adiguzel U, Tamer L, Yildirim O, Oz O, Vatansever H. Serum oxidant/antioxidant balance in exfoliation syndrome. Clin Experiment Ophthalmol. 2005;33(1):63-6.15. Fingert JH, Alward WL, Kwon YH, Wang K, Streb LM, Sheffield VC, et al. LOXL1 mutations are associated with exfoliation syndrome in patients from the midwestern United States. Am J Ophthalmol. 2007;144(6):974-975.16. Kenyon K, Modi WS, Contente S, Friedman RM. A novel human cDNA with a predicted protein similar to lysyl oxidase maps to chromosome 15q24-q25. J Biol Chem. 1993;268(25):18435-7. 17. Gottanka J, Kuhlmann A, Scholz M, Johnson DH, Lütjen-Drecoll E. Pathophysiologic changes in the optic nerves of eyes with primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci. 2005;46(11):4170-81.


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OriginalArticles

Split Macular Fixation- Our Experience

Address for Correspondance: Thomas George T, Regional Institute of Ophthalmology, Trivandrum

Introduction

It has been taught for a long time that patients with advanced glaucoma stand a risk of total loss of vision with surgical therapy. Von Graefe introduced glaucoma surgery in 1856; he noted that central vision may be involved postoperatively in patients with constricted visual fields1. Sugar is quoted as: “In a patient with simple glaucoma who sees with only one eye and who has a small central field of 15 degrees or less, medical treatment should be the only treatment.”2. Kolker et al reported sudden loss of central vision also occurred following cataract extraction (8.7%) and glaucoma filtration surgery (13.6%). No patient lost central vision suddenly following surgery when fixation was not split on field charting at the time of operation3. After this landmark study It became routine to explain about wipe out or snuff out of vision after glaucoma surgery. Glaucoma surgeons the world over became more reluctant to operate on advanced glaucoma cases because of fear of wipe out.

Some other experts denied the possibility of wipe out altogether 4, 5. More recent study by Topouzis et al concluded that there was no risk of wipe out 6. But his series of patients had no patient with a split macular fixation. The AGIS study which is quoted as the landmark study also did not specifically address the situation where macular split was present on fields7. This leaves a lacuna in our knowledge which we tried to fill with our study.

Objective

The objective of my study is to assess the risk of loss of central of central vision in patients with split macular fixation undergoing surgical therapy

Design

This was a retrospective study based on our medical records.

Materials and methods

Macular threshold was obtained using the macular programme on the Humphrey field analyzer (model 720i). This programme uses a full threshold strategy and a size V stimulus size. Split macular fixation was defined for the study as one of the four points abutting fixation on the macular programme having a sensitivity of single digit (less than 10, normal threshold in these locations are in the 30s) with an adjacent point on the same side of fixation also being less than 10 (see fig 1 below) 8.

Fig.1 Split macular fixation is defined as single digit sensitivity at 1 of the four points abutting fixation with at least one adjacent

point being the same. Here in this case the upper right hand side point next to fixation is in single digit and the adjacent points are

also single digit sensitivity.

Thomas George.T MS

Abstract

1. Objective: To assess the risk of loss of central vision in patients with split macular fixation undergoing surgical therapy

2. Design: Retrospective study based on our medical records.

3. Participants and/or controls: 44 eyes of 37 patients with split macular fixation that presented to our glaucoma clinic and underwent filtering surgery from June 2004 to May 2009 were analyzed.

4. Intervention or methods: 32 eyes underwent trabeculectomy, rest underwent combined cataract and filtering surgery

5. Main outcome measure: Post operative intraocular pressure, change in visual acuity and visual fields(central 5°)

6. Results: 1 patient wiped out after surgery. Chances of loss of central vision are low even if central 5° shows split fixation. (2.27% among surgical patients). 2 had decrease in quality of vision due to prolonged hypotony (4.54%).

7. Conclusions: Risk of wipe out with surgery low (93.19% had good vision. 97.73 did not wipe out)). So surgery should not be withheld due to risk of wipe out when target intraocular pressure cannot be maintained medically.

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44 eyes of 37 patients with split macular fixation that presented to our glaucoma clinic and underwent filtering surgery from June 2004 to May 2009 were analyzed. All patients were deemed not to have achieved target intraocular pressures with maximal medical therapy.

The mean age of patients included was 52.75 years (range 24-77, standard deviation of 12.37). There were 19 male patients and 18 female patients. The mean pre operative intraocular pressure was 33.38 mmHg (range 52 -19, standard deviation 9.77).

The diagnoses of these eyes were variable, though primary open angle glaucoma accounted for most cases. 26 eyes had primary open angle glaucoma, 12 had chronic angle closure glaucoma and 3 had combined primary open angle glaucoma and angle closure glaucoma. There was 1 eye with angle recession glaucoma and 2 eyes with intractable probably steroid induced glaucoma (2 eyes of the same patient. In a patient who self medicated for years for allergic conjunctivitis with dexamethasone drops).

Visual acuity ranged from 1/60 (4 eyes) to 6/6 (10 eyes) preoperatively.

Intervention

32 eyes underwent trabeculectomy; rest underwent combined cataract and filtering surgery. The decision for combined surgery was made whenever the cataract was visually significant.

Results

The mean pre operative intraocular pressure was 33.38 mmHg (range 52 -19, standard deviation 9.77). Post operatively the mean intraocular pressures achieved at 2 months was 11.31mmHg (range 4-18, Standard deviation 3.51). There was a mean improvement in visual acuity of 0.59 lines on Snellen acuity (range of -2 to 5 lines, SD of 1.69). The field thresholds were not significantly different pre and post operatively once long term fluctuation in field thresholds were accounted for (except in the 1 patient who wiped out where all sensitivity was lost).

1 patient wiped out after surgery. This patient had a preoperative visual acuity of 6/60 and underwent a combined cataract and filtering surgery. He had no perception of light on the 2nd postoperative day. He was a hypertensive on treatment. He had a hyphema on the 2nd postoperative day with a visible clot in the anterior chamber in the surgical area. His IOP was 54 mmHg on that day. This was controlled with medical measures, but his vision was lost. The rate of wipe out in our study was thus 1/44 (2.27% with a confidence interval of 0 to 5.283%)

2 had decrease in quality of vision (4.54% CI 0.28 -8.80%). 1 patient who was 6/6 preoperatively stabilized at 6/12 after 2

months of hypotony. Another patient who had a preoperative vision of 6/18 stabilized at 6/36 due to a macular hemorrhage noted 1 week post operatively. Both these incidents were probably due to hypotony.

Discussion

From our study we find that the risk of wipeout is less than what was thought before. The risk was estimated to be in the range of 10% in the past (8.7% for cataract extraction and 13.6% for glaucoma surgery) 2. Our study gave us a wipe out rate of 2.27%. The 95% confidence interval calculated on this rate placed the actual risk of wipe out between 0 to 5.283%. If we look at the brighter side 97.73 % of eyes did not wipe out. Therefore almost all eyes benefit from surgery as an option to lower intraocular pressure even with advanced glaucoma with split macular fixation.

On the other hand unlike the more recent literature suggesting that wipe out does not exist6. We can say that there is a definite risk of wipe out. Even though the risk is lower than was previously thought.

Hence surgery as an option to achieve target intraocular pressure should not be withheld when medical therapy is inadequate. The risk of wipe out with surgery is much lower than risk of loss of visual function from uncontrolled glaucoma.

The risk of decrease in visual acuity was 4.54%. These were the consequence of hypotony in our series. Sudden hypotony can cause macular hemorrhage which is another cause for wipe out and degradation of vision. Long standing hypotony can decrease visual acuity and cause metamorphopsia. Hence hypotony lasting over 6 weeks should be viewed seriously and treated.

Conclusions

Risk of wipe out and loss of central vision with surgery are much lower than was thought (93.19% had good vision. 97.73 did not wipe out)). So surgery should not be withheld due to risk of wipe out when target intraocular pressure cannot be maintained medically. In our series hypotony accounted for more of the decrease in visual acuity than a spike in intraocular pressure or cataract formation post operatively. The one case of wipe out however was due to a post operative spike in intraocular pressure.

References 1. A. Von Graefe, Beitrage zur Pathologie und Therapie des Glaucoms. Albrecht von Graefe’s Arch, Klin Ophthalmol 15 (1869),3.2. H.S. Sugar, The glaucomas (2nd Ed), Hoeber, New York (1957), 261.3. A.E. Kolker, Visual prognosis in advanced glaucoma a comparison of medical and surgical therapy for retention of vision in 101 eyes with advanced glaucoma, Trans Am Ophthalmol Soc (1977), vol. LXXV, 529–555.

Thomas George - Split macular fixation


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4. P.R. Lichter and J.G. Ravin, Risks of sudden visual loss after glaucoma surgery, Am J Ophthalmol 1974:78:1009-1013.5. P.A. Chandler and W.M. Grant, Lectures on glaucoma, Lea and Febiger, Philadelphia (1965), 136.6. Topoouziz F et al. Risk of sudden visual loss following filtration surgery in end stage glaucoma; Am Journal Ophthalmol. 2006:142;199-200.

7. Kim J, Dally LG, Ederer F, Gaasterland DE, VanVeldhuisen PC, Blackwell B, Sullivan EK, Prum B, Shafranov G, Beck A, Spaeth GL; AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 14. Distinguishing progression of glaucoma from visual field fluctuations. Ophthalmology. 2004; 111(11):2109-16. 8. Thomas R, George R. Interpreting automated perimetry. Ind J Ophthalmol. 2001:49;125-140.

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339

Original Articles

Plasma fibrinogen levels and its relation to diabetic retinopathy

Neetha Kuzhuppilly I R, MS, Vijaya Pai H, MS

Address for Correspondance: Neetha Kuzhuppilly I R, Kasturba Medical College, Manipal, Karnataka.

ABSTRACT

Aim: To assess the relationship between plasma fibrinogen levels and diabetic retinopathy.

Materials and methods: 122 diabetics were evaluated for diabetic retinopathy. Blood pressure, plasma fibrinogen, fasting and post prandial glucose were determined. Independent sample‘t’ test was used for comparison between diabetics with and without retinopathy.

Results: Fibrinogen levels were significantly higher in diabetics with retinopathy (p=0.004). Regression analysis showed that duration of diabetes and fibrinogen levels were independent factors associated with the existence of retinopathy.

Conclusion: High plasma fibrinogen levels contribute significantly to the development of diabetic retinopathy.

Key words: Plasma Fibrinogen, Diabetic Retinopathy, Diabetes mellitus

Introduction

In the developed world, diabetic retinopathy is the leading cause of blindness in patients under 60 years of age. According to the World Health Organization (WHO) report, dated 2004, India has 31.7 million diabetics, and the number is expected to increase to a staggering 79.4 million by 2030. [1] In India, the prevalence of Diabetic Retinopathy amongst diabetics is 17–27%. [2],[3],[4],[5] Prevalence of diabetic retinopathy at the time of diagnosis is 7.3%. [5]

There are numerous factors associated with the development of diabetic retinopathy. In recent years there has been an increased interest in the hematological changes associated with diabetic retinopathy. Increase in blood viscosity and other hematological changes are now seen to contribute to the development of diabetic retinopathy much more than previously known.[6],[7],[8],[9] Elevation of Plasma Fibrinogen is thought to be one of the major factors associated with this increase in blood viscosity. Keeping this in mind, we did this study to assess the relationship between Diabetic Retinopathy and Plasma Fibrinogen.

Till date, to the best of our knowledge, no study has been conducted on an Indian population in search of a modifiable

risk factor like Plasma Fibrinogen in the development of diabetic retinopathy.

Materials and Methods

It was a Prospective, Observational, Comparative study. The study period was from September 2006 to August 2008.

All known cases of Diabetes Mellitus [DM] & newly diagnosed cases of diabetes mellitus, with Fasting plasma glucose (FPG) >126mg% or Post prandial plasma glucose (PPPG) >200mg% were included in the study.

Cases with systemic illnesses altering the blood coagulation profile, inherited diseases which cause either hypercoagulability or bleeding tendencies, patients on anticoagulants, patients with liver, cardiac or renal failure, or with opacities of ocular media obstructing view of the fundus were excluded.

All the patients enrolled in the study were explained about the study and a written informed consent was taken. The institutional ethics committee cleared the project. History of the patients regarding the ocular complaints, type of diabetes, duration of diabetes and treatment, and other systemic illnesses were noted. Ocular examination included best corrected distance and near vision, anterior segment examination with the slit lamp, intra ocular pressure measurement by Goldmann applanation tonometry, fundus examination with direct ophthalmoscopy / indirect ophthalmoscopy / examination with 90 D lens at the slit lamp. Fundus fluorescein angiography was done as and when indicated. Blood pressure was recorded in all patients. Blood investigations like FPG (Fasting Plasma Glucose), PPPG (Post Prandial Plasma Glucose) and Plasma Fibrinogen were done.

Based on the fundus examination findings, the patients were classified into two groups. Group 1 included patients with diabetic retinopathy and Group 2 included patients with no diabetic retinopathy.

Patients in Group 1 were graded as per the ETDRS (Early Treatment Diabetic Retinopathy Study) classification of diabetic retinopathy. If a patient had different grades of retinopathy in both eyes, the more severe grade was taken into consideration.

For the estimation of plasma fibrinogen, 2 ml of venous blood was collected in a citrated container and fibrinogen levels were estimated using a standardized 2 step procedure.[10]

The principle of the procedure was that the Fibrinogen in


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the citrated plasma is precipitated using calcium chloride solution. The precipitate is re-dissolved in sodium hydroxide and the protein content is estimated by an auto analyzer. The normal plasma fibrinogen level ranges from 200 to 400 mg/dl.

The sample size of the number of participants required in each study group, ‘m’, was determined by the formula,

Where z (1-a/2) and z (1-b) represent percentage points of the normal distribution for statistical significance level and power, respectively and D2 represents the standardized difference (i.e. the mean difference divided by its standard deviation). In the study, statistical significance level was taken as 5% and power was taken as 90%. Using the above mentioned formula, it was calculated that 59.47 [rounded off to 60 patients] were required to be included in each group of the study.

SPSS version 15 for windows was the statistical package used for all statistical analysis of data collected in the course of the study. The procedures followed were in accordance with the ethical standards of the institutional Ethics Committee.

Results

A total of 122 patients with Type 2 diabetes were included in the study.

There were 61 patients in each group, i.e. Group 1 [With Diabetic Retinopathy] and Group 2 [With No Diabetic Retinopathy]. In Group 1, there were 43 patients with Non Proliferative Diabetic Retinopathy [NPDR] and 18 patients with Proliferative Diabetic Retinopathy [PDR].

85 (69.7%) male and 37(30.3%) female patients were enrolled in the study. Group 1 had 42 men and 19 women; Group 2 had 43 men and 18 women. Using Chi square test, it was seen that the gender was not a contributing factor to the outcome of the study as both men and women were equally distributed in the two groups (p value = 0.844).

Both the groups had similar age distribution pattern and no significant difference existed between them. In Group1, the mean age was 54.84 yrs (range 27-75yrs) and in Group 2, the mean age was 55.95 yrs (range 26-74 yrs).

Table 1 shows the duration of diabetes in the two groups. It is seen that the majority of patients with ‘no retinopathy’ had lesser duration of diabetes, compared to patients with diabetic retinopathy. 80.32% of patients with diabetic retinopathy had duration of diabetes >5 yrs. Mean duration

of diabetes in Group 1 was 10.6 yrs (SD 7.39) and in Group 2 was 6.3 yrs (SD 5.75). On analyzing this with independent samples t test, this difference was seen to be significant, with a p value <0.001.

64 patients included in the study were diagnosed hypertensives and 58 were non hypertensives. On analysis of the actual values of the blood pressures in the two groups, it was seen that the mean systolic blood pressure in Group 1, with diabetic retinopathy was 141.48 mm Hg (SD 20.35) and in Group 2, with no diabetic retinopathy, was 133.34mm Hg (SD 15.88). Independent samples t test showed a significant difference (p=0.015). There was no significant difference in the diastolic blood pressures between the 2 groups. The mean diastolic blood pressure in Group 1 was 85.48 mm Hg (SD 9.59) and in Group 2 was 82.43 mm Hg (SD 8.13).

The fasting (FPG) and post prandial plasma glucose (PPPG) were estimated in all the patients. The mean values of both groups were compared, as seen in Table 2. Both the fasting and post prandial plasma glucose levels were significantly higher in Group 1 with diabetic retinopathy.

Table 3 shows Plasma Fibrinogen and its relation with diabetic retinopathy. The plasma fibrinogen values were significantly higher in the group with Diabetic Retinopathy. The mean values in both groups fall within the normal range of fibrinogen in plasma, but the difference in the two groups was significant.

ANOVA Tukey HSD test was done to analyze the relationship between fibrinogen levels among the three groups of NPDR, PDR and No Diabetic Retinopathy. It showed a significant difference in between the three groups with the p value being 0.016 (Table 4). Significant difference existed between the ‘No Retinopathy’ group and the NPDR group, but there was no significant difference between the ‘No Retinopathy’ group and the PDR group, probably because of the smaller number of patients in the PDR group [18 patients]. Also, no difference in fibrinogen levels existed between the NPDR and PDR groups.

The relationship of Plasma fibrinogen with other variables in the study was assessed. Spearman correlation coefficient was estimated to find out if any relation existed between plasma fibrinogen levels and duration of diabetes, blood pressures, and plasma glucose levels (Table 5). Significant correlation was present between Plasma fibrinogen levels and the Diastolic BP and Fasting glucose.

Independent Student t test was done to determine if there was association between fibrinogen levels and the sex of the patient. The mean plasma fibrinogen in the male patients was 274.14mg% (SD 111.626) and in the female patients was 282.49mg% (SD 117.123). The fibrinogen values were higher among the female patients, but the difference was

341

Neetha K, Vijaya Pai- Plasma fibrinogen & DR

not significant (p=0.715).

Logistic Regression Analysis was conducted to see if the association noted between Plasma Fibrinogen and Diabetic retinopathy is independent of the other associations of retinopathy. It is seen from table 6 that, even after controlling for the duration, blood pressure, glucose levels and age, plasma fibrinogen is independently associated with Diabetic Retinopathy. The duration of diabetes was the other major independent risk factor for diabetic retinopathy in this study.

Discussion

Diabetes mellitus is considered to be associated with a state of hypercoagulability.[6],[7],[8],[9] Elevated Plasma Fibrinogen levels are thought to contribute significantly to this hypercoagulability.[11] Fibrinogen studies collaboration and various other studies have found that increased fibrinogen levels are associated with major systemic morbidity like coronary artery disease, stroke etc.[12] Asakawa and Fujisawa have shown that increased fibrinogen is associated with worsening renal function and also retinopathy.[13],[14] In our study, we wanted to explore the significance of this association of plasma fibrinogen and the diabetic retinopathy, which is of major concern to the ophthalmologists.

Our study demonstrates that Plasma Fibrinogen levels are significantly in patients with diabetic retinopathy. Also, it is seen that the duration of diabetes, raised blood pressure, and uncontrolled glucose levels are significant contributors to retinopathy development. Among these, the duration of DM appears to be most significant factor.

These findings are consistent with those of the other studies which have established that the duration of diabetes is an important factor in the development of diabetic retinopathy.[15],[16],[17] Blood pressure and glucose levels also contribute to the development of diabetic retinopathy, as reported by previous studies and is in agreement with the present study.[18],[19],[20],[21]

The age of the patient did not seem to affect presence of diabetic retinopathy. There is no significant increase of retinopathy with increasing age. This is probably due to the fact that the duration of diabetes may be a more important indicator than the actual age. The exact duration of diabetes may sometimes be difficult to determine and patients do occasionally present with diabetic retinopathy soon after the diagnosis of diabetes.[22]

On analyzing the Fibrinogen values, it was seen that although the values may fall within the normal range in both the groups, the values were significantly higher in the retinopathy group. On further comparison within the retinopathy group, no significant difference was seen between the NPDR and PDR groups, suggesting that plasma fibrinogen may not contribute to the severity of retinopathy. This can also be an

erroneous finding due to the smaller number of patients in the PDR group. This finding is in agreement with the reports of Fujisawa and Asakawa.[13],[14] They found that plasma fibrinogen is independently associated with existence of diabetic retinopathy, but not significantly different when comparing different grades of retinopathy.

It is also seen that significant correlation exists between the plasma fibrinogen levels and Diastolic BP and Fasting glucose levels. Hypertension and uncontrolled glucose levels may be associated with raised fibrinogen levels and thus may have secondary effect on the development of retinopathy. In contrast to earlier findings, no correlation was noted in the present study between fibrinogen levels and the age or gender of the patient.[23] The current study was unable to analyze lifestyle factors like smoking, BMI, lipid profile that are thought to have an influence on fibrinogen levels.[11],[23] The Duration of DM, which was seen to be the most important contributory factor in our study, did not show any correlation with Plasma Fibrinogen levels, indicating that their contributions are independent of each other.

In the current study, we have proven that diabetic retinopathy is independently associated with higher Plasma fibrinogen, even after controlling for the other major risk factor- duration of diabetes. Also, it is independent of the blood pressure and glucose levels. Two of the previous studies have commented on fibrinogen being an independent risk factor for retinopathy after controlling for nephropathy and duration of diabetes, but none have noted it being an independent risk factor after controlling for the plasma glucose and blood pressure.[13, 14]

The findings of this study have a number of important implications for future practice. The study may be of practical worth, if treatment measures can be found that can safely lower the Plasma Fibrinogen levels, either in the form of medications or lifestyle modifications.[11],[23],[24],[25]

Prevention of diabetic retinopathy may be possible in such a case. Also, fibrinogen levels pre-treatment and during on-going treatment could be a potential indicator for efficacy. Fibrinogen levels could be a potential marker for the prediction and prevention of diabetic retinopathy. It’s something to look forward to, for the ophthalmologist, the patient and the society as a whole.

The future trends of diabetic retinopathy management would then probably be targeted at preventing the key hemodynamic changes occurring in diabetic retinopathy; and curbing retinopathy in its infancy, minimizing the sequelae and subsequent visual loss among the patients.

References

1. Wild S, Roglic G, Green A, et al. Global Prevalence of Diabetic Retinopathy, Estimates for the Year 2000 And Projections for 2030.


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Diabetes Care 2004; 27:1047 – 53.

2. Rema M, Premkumar S, Anitha B, et al. Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural Epidemiology Study (CURES) eye study, I. Invest Ophthalmol Vis Sci 2005; 46:2328-33.

3. Dandona L, Dandona R, Naduvilath TJ, et al. Population based assessment of diabetic retinopathy in an urban population in southern India. Br J Ophthalmol 1999; 83:937-40.

4. Narendran V, John RK, Raghuram A, et al. Diabetic retinopathy among self reported diabetics in southern India: a population based assessment. Br J Ophthalmol 2002; 86:1014-8.

5. Rema M, Deepa R, Mohan V. Prevalence of retinopathy at diagnosis among type 2 diabetic patients attending a diabetic centre in South India. Br J Ophthalmol 2000; 84:1058-60.

6. Vekasi J, Marton ZS, Kesmarky G, et al. Hemorheological alterations in patients with diabetic retinopathy. Clin Hemorheol Microcirc 2001; 24:59-64.

7. Shin S, Ku Y, Babu N, et al. Erythrocyte deformability and its variation in diabetes mellitus. Indian J Exp Biol 2007; 45:121-8.

8. Negrean V, Suciu I, Sâmpelean D, et al. Rheological changes in diabetic microangiopathy. Rom J Intern Med 2004; 42:407-13.

9. Bae SH, Lee J, Roh KH, et al. Platelet activation in patients with diabetic retinopathy. Korean J Ophthalmol 2003; 17:140-4.

10. Varley H, Gowenlock AH, Bell M. Practical Clinical Biochemistry. 5th ed. London: William Heinemann Medical Books Ltd; 1984.

11. Klein RL, Hunter SJ, Jenkins AJ, et al; DCCT/ECIC STUDY GROUP.

Fibrinogen is a marker for nephropathy and peripheral vascular disease in type 1 diabetes: studies of plasma fibrinogen and fibrinogen gene polymorphism in the DCCT/EDIC cohort. Diabetes Care 2003; 26:1439-48.

12. Fibrinogen Studies Collaboration, Danesh J, Lewington S, Thompson SG, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005; 294:1799-809.

13. Asakawa H, Tokunaga K, Kawakami F. Elevation of fibrinogen and thrombin-antithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy. J Diabetes Complications 2000; 14:121-6.

14. Fujisawa T, Ikegami H, Yamato E, et al. Association of plasma fibrinogen level and blood pressure with diabetic retinopathy, and renal complications associated with proliferative diabetic retinopathy, in Type 2 diabetes mellitus. Diabet Med 1999; 16:522-6

15. Frank RN, Hoffman WH, Podgor MJ, et al. Retinopathy in juvenile-onset type I diabetes of short duration. Diabetes 1982; 31:874-82.

16. Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 1984; 102:520-6.

17. Palmberg P, Smith M, Waltman S, et al. The natural history of retinopathy in insulin-dependent juvenile-onset diabetes. Ophthalmology 1981; 88:613-8.

18. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK

Table 1: Duration of Diabetes

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Prospective Diabetes Study Group. BMJ 1998; 317:703-13.

19. Knowler WC, Bennett PH, Ballintine EJ. Increased incidence of retinopathy in diabetics with elevated blood pressure. A six-year follow-up study in Pima Indians. N Engl J Med 1980; 302:645-50.

20. Klein R, Klein BE, Moss SE, et al. Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med 1989; 149:2427-32.

21. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:977-86.

22. Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy

when age at diagnosis is 30 or more years. Arch Ophthalmol 1984; 102:527-32.

23. Pajak A, Broda G, Manolio TA, et al. Constitutional, biochemical and lifestyle correlates of fibrinogen and factor VII activity in Polish urban and rural populations. Int J Epidemiol 1998; 27:953-61.

24. Maison P, Mennen L, Sapinho D, et al; D.E.S.I.R. Study Group. A pharmacoepidemiological assessment of the effect of statins and fibrates on fibrinogen concentration. Atherosclerosis 2002; 160:155-60.

25. Shah HD, Parikh KH, Chag MC, et al. Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions. Exp Clin Cardiol 2007; 12:91-6.

Table 2: Plasma glucose levels and Diabetic Retinopathy

Table 3: Plasma Fibrinogen and Diabetic Retinopathy



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Table 4: ANOVA Tukey HSD test

Table 5: Correlating Fibrinogen with other variables

*The mean plasma fibrinogen level in ‘No DR’=247.74mg%, PDR=297.56mg%, NPDR=308.98mg%

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Table 6: Independent Risk Factors: Logistic Regression Analysis


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OriginalArticle

Visual outcome and risk of sudden visual loss following Trabeculectomy in End – Stage Glaucoma

Address for Correspondance: Uma Eye Clinic, Anna Nagar, Chennai – 40

M. Chockalingam DNB FRCS (Glasgow) PGDHM

Introduction

The management of glaucoma has always centered upon methods to reduce intraocular pressure since this is the only modifiable cause of glaucoma. With the advent of newer medications to treat glaucoma, there has been a steady decline in number of eyes undergoing filtration surgery including trabeculectomy. Glaucoma filtration surgery is now resorted to as a last step when the entire armamentarium of medical management has been exhausted. Therefore, there

is an increasing tendency of trabeculectomy being done in eyes with advanced glaucoma. However, there is a concern that filtering procedure in eyes with advanced glaucoma may be associated with a risk of immediate unexplained post – operative visual field loss which includes fixation, this being termed as “wipe – out syndrome”. 1 – 4 This loss of central visual field can follow an otherwise uneventful surgery with none of the complications usually following trabeculectomy like cataract, suprachoroidal or vitreous hemorrhage, macular edema, uveitis etc being present. There are various reports about the incidence of “wipe – out” phenomenon with some reporting “wipe – out” in 14% of patients with advanced field loss 4 whereas others regard this phenomenon as extremely rare. 5

The current study was undertaken to prospectively evaluate the effect of trabeculectomy on visual acuity and visual fields in patients with end – stage glaucoma during the immediate post – operative period and to assess the risk of sudden visual field loss.

Patients And Methods

In this prospective, consecutive case series study, subjects with end – stage glaucoma who were due to undergo trabeculectomy between August 2006 to September 2007 were enrolled. The study was done in the glaucoma services of a tertiary eye care hospital. End – stage glaucoma was defined on the basis of visual field results by adopting the Advanced Glaucoma Intervention Study (AGIS) grading system A10 adopting an AGIS score of greater than 16. In visual fields with AGIS score greater than 16, only a central island of vision is present while most of the visual field points have no sensitivity at all (0 dB).

A written informed consent was obtained from all the patients. Pre – operatively a detailed history was obtained with specific inputs about use of and number of anti – glaucoma medications, use of systemic medications and prior intraocular surgeries. Best corrected visual acuity was measured with a retroilluminated ETDRS chart. A baseline ophthalmic evaluation was performed along with Goldmann applanation tonometry, gonioscopy, dilated fundus examination with specific assessment of cup – to – disc ratio were performed. The lens status, type of glaucoma, type and number of preoperative antiglaucoma were documented. All patients enrolled in the study were subjected to 24 – 2 SITA STANDARD visual field test (Humphrey Field Analyzer) and a Macular Threshold program.

A fornix based trabeculectomy was done in all subjects by

Aim: To evaluate the effect of trabeculectomy on visual acuity and visual fields and assess the risk of sudden visual loss in patients with end – stage glaucoma.

Design: Prospective, interventional, consecutive case series.

Materials And Methods: This is a prospective study done on patients with end – stage glaucoma with advanced visual field loss (Advanced Glaucoma Intervention Study visual field score over 16) who underwent Trabeculectomy augmented with Mitomycin – C. The patients were followed for three months following surgery. At final follow – up, the main outcomes measured included changes in best corrected visual acuity, Intraocular pressure (IOP) levels, number of anti – glaucoma medications used, mean deviation (MD) in visual fields, number of points among the four central visual field points with a sensitivity less than 5 dB and in mean sensitivity of four central visual field points.

Results: Twelve patients (12 eyes) were enrolled. Mean Age was 62 years (range 50 – 77). Surgery resulted in a statistically significant reduction of IOP by 15.2 + 7.9 mm Hg (p < 0.001) and a decrease in number of post – operative anti – glaucoma medications required (p< 0.001). Three months after surgery, there was no significant change in visual acuity. Mean value in deviation of visual fields was – 28.5 + 3.5 dB and – 27.8 + 3.4 dB before and three months after surgery respectively. There was no significant change (- 0.8 + 0.3; p = 0.338) in the mean sensitivity of the central four points. There were no intra operative complications. Transient hypotony occurred in one eye.

Conclusion: In this series of patients with end – stage glaucoma followed for three months after surgery, trabeculectomy reduced the intraocular pressure effectively and vision was preserved with no occurrence of “wipe – out” phenomenon.

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a single surgeon. The technique involved a fornix based conjunctival flap and a partial thickness 4 mm X 3.5 mm triangular scleral flap. In all patients, the anti - metabolite Mitomycin – C (0.2 mg/ ml) was applied with a weck sponge under the conjunctival flap for three minutes before the creation of the partial thickness scleral flap. The area was copiously irrigated with 15 – 20 ml of balanced salt solution (BSS) after removal of the weck sponge. A paracentesis was done. The sclerostomy was done with a surgical knife and Kelly’s punch followed by an iridectomy. The scleral flap was sutured with two releasable 10 – 0 nylon sutures in the bases and one fixed 10 – 0 nylon suture in the apex. BSS was injected through the paracentesis tract to test the stability of the anterior chamber and to see for visible leak around the scleral flap. The conjunctival flap was closed with two 8.0 vicryl sutures with slight overriding of the conjunctiva over the cornea.

The patients were examined at 1st day, 1 week, 2 weeks, 6 weeks and 3 months after surgery. Additional visits were scheduled as clinically warranted. At each visit, visual acuity, number of antiglaucoma medications needed, details IOP and optic disk status were noted. The incidence of post – operative complications such as flat or shallow anterior chamber, hypotony, macular edema, choroidal detachment and bleb leak were recorded at each visit. Hypotony was

defined as IOP as less than 6 mm Hg and was considered to be transient when it lasted less than 15 days. Visual fields were repeated for all the eyes 3 months after surgery.

The main measures studied at 3 months after surgery included (1) Best corrected visual acuity (2) Mean Deviation (MD) of visual fields (3) Number of central visual field points with sensitivity of less than 5 dB (4) Mean sensitivity of the four central points (5) Number of glaucoma medications needed

Relationships of outcome measures with baseline characteristics were evaluated with independent t test for normally distributed variables. Spearman rank correlation test and Wilcoxon signed – rank test were used for variables that showed no normality. All tests were considered to be statistically significant if p < 0.001.

Results

Twelve consecutive eyes of 12 patients (M: F = 7: 5) who fulfilled the criteria were recruited in the study. The mean AGIS score of the eyes enrolled in the study was 18.24 + 0.58 (range 16 – 20). The demographic and baseline characteristics are summarized in Table 1.

Table 1 – Baseline Clinical Characteristics Of 12 Eyes With End Stage Glaucoma Undergoing Trabeculectomy

Chockalingam- Risk of wipe out after trabeculectomy


348


Trabeculectomy alone was performed in all 12 eyes. Two patients were blind in the fellow eye at the time of presentation, the blindness being attributable to glaucoma in both of them. There was no intra – operative complications. Transient hypotony occurred in one eye which resolved with conservative management. There were no cases of flat anterior chamber, macular edema or choroidal detachment. All twelve patients required removal of one releasable suture with eight of them requiring further removal of the other releasable suture. One patient needed argon laser suturelysis of the fixed suture. There was one patient with transient hypotony which responded to conservative management comprising of patching and use of atropine eye drops and ointment.

There was no significant change in the mean LogMAR visual acuity (p = 0.73) 3 months after filtration surgery. We achieved a significant reduction of IOP from 28.3 + 7.9 mm Hg pre – operatively to 13.2 + 4.5 mm Hg 3 months after surgery. The reduction in IOP resulted in a reduced need for post – operative anti glaucoma agents from 2.6 + 0.5 at baseline to 0.3 + 0.5 at the end of final follow up (p < 001). Ten patients (83.33%) of patients achieved optimal IOP levels with no need for post operative anti glaucoma medications while 2 patients (16.66%) required one or more anti – glaucoma agents. The change in mean deviation (MD) 3 months after

surgery was very minimal (decrease by 0.7 + 0.1) and did not reach significance levels (p = 0.338). Similarly, there was no significant change in the mean number of central visual field points with sensitivity less than 5 dB (2.6 + 0.9 and 2.5 + 0.9 before and after surgery; p = 0.317). There was a marginal improvement in the mean sensitivity of the four central visual field points by 0.4 + 0.1 (5.1 + 4.7 and 5.5 + 4.8 before and after surgery; p = 0.36). The mean change in visual acuity and visual fields 3 months following glaucoma filtration surgery along with change in number of medications required 3 months following glaucoma filtration surgery is shown in shown in table 2. None of the patients developed “wipe – out” phenomenon.

Discussion

“Wipe – out” phenomenon has been described as sudden reduction of visual acuity after filtration surgery in end – stage glaucoma, with no apparent ocular pathology to explain this decline.1 Kolker and associates reported an incidence of 13.6% of central vision loss in the immediate post – operative period.2 Recent reports showed that the risk of “wipe – out” is lower than 1% and is more likely to occur in older patient with macular splitting in the pre operative visual fields.1 Although the exact mechanism of wipe – out is not known, it has been suggested that it can happen due to –

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Chockalingam- Risk of wipe out after trabeculectomy

(1) Sudden, intra – operative ocular hypotony during glaucoma surgery resulting in optic nerve hemorrhage and decreased perfusion to the optic nerve head. It may also induce a micro – embolic episode that could damage the remaining nerve fibers. 5 – 7

(2) Post operative hypotony with maculopathy(3) Post operative increased IOP resulting in macular ischemia

There is a great diversity of report on the incidence of unexplained visual loss after filtration surgery with some reporting incidence as high as 13.6% 2 to some reporting no association between surgical intervention and reduction of central visual fields. 6, 8

In our study, we used the AGIS scoring system which ensured recruitment of a homogenous group of patients with end – staged glaucoma. The use of the four central visual field points in addition to Mean Deviation (MD) allowed accurate quantification of post – operative visual field change. In end – stage glaucoma where most of visual field points have no sensitivity at all (0 dB), the mean deviation (MD) representing all visual fields points may be less sensitive to small changes, which could occur in the remaining central island of vision. By the use of the four central visual field points as an outcome measure, we are able to quantify small changes that could occur in the remaining central visual field. Results of our study showed that none of the participants developed “wipe – out” phenomenon within the 3 months postoperative follow up period.

In conclusion, our study shows that glaucoma surgery has a beneficial effect in the vast majority of patients with advanced visual field loss and elevated intraocular pressure. We should point out that our sample size was small. Although our study achieved statistical significance, the sample size may not be large enough to identify “wipe – out” cases that occur in very rare instances. However, the prospective design, homogenous study population, standardization of

surgery and thorough follow – up of all participants with systematic evaluation of visual acuity and central visual fields provide a high level of accuracy and reliability in the information obtained. Meticulous post – operative follow up, intraocular pressure assessment and using methods for post – operative intraocular pressure titration like removal of releasable sutures, argon – laser suturelysis, all ensured that elevated IOP was not sustained in the post – operative period. Therefore, we conclude that glaucoma surgery as an option should be pursued in such patients without the fear of “wipe – out”. However, further prospective studies with a larger number of patients, would be required to better define the risk and risk factors for the “wipe – out” phenomenon after filtration surgery.

Reference(1) Costa VP, Smith M, Spaeth GL et al. Loss of visual acuity after trabeculectomy, Ophthalmology 1993; 100: 599 – 612(2) Kolker AE, Visual prognosis in advanced glaucoma: a comparison of medical and surgical therapy for retention of vision in 101 eyes with advanced glaucoma. Trans Am Opthalmol Soc 1977; 75: 539 – 555(3) Aggarwal SP, Hendeles S. Risk of sudden visual loss following trabeculectomy in advanced primary open angle glaucoma. Br J Ophthalmol 1986; 70: 97 – 99(4) Otto J. Loss of point of fixation after glaucoma surgery. Trans Am Ophthalmol 1974; 71: 124 – 131(5) Lichter PR, Ravin JG. Risk of sudden visual loss after glaucoma surgery. Am J Ophthalmol 1974; 78: 1009 – 1013(6) O’ Connell EJ, Karseras AG. Intraocular surgery in advanced glaucoma. Br J Ophthalmol 1976; 60: 124 – 131(7) Martinez JA, Brown RH, Lynch MG et al. Risk of post – operative visual loss in advanced glaucoma. Am J Ophthalmol 1993; 115: 332 – 337(8) Topouzis F, Tranos P, Koskosas A et al. Risk of sudden visual loss following filtration surgery in end – stage glaucoma. Am J Ophthalmol 2005; 140: 661 – 666

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BriefCommunication

Prevalance of sleep apnoea in patients with open angle glaucoma

Rani Menon, MS, FRCS (Edin), Firosh Khan, MD, DM (Neuro)

Abstract

Aim:- To determine the prevalence of sleep apnoea in patients with glaucoma.

Methods:- 34 Patients with open angle glaucoma underwent overnight polysomnogram. Sleep apnoea was graded into mild ,moderately severe and severe according to AHI (Apnea Hypopnea Index) < 15 mild15– 30 moderate > 30 severe

Results:- Out of 34 patients with glaucoma 10(29.41%) were found to have severe sleep apnoea (AHI > 30). 13(38.23%) had moderately severe sleep apnoea (AHI 15 to 30) and11(32.35%) had mild sleep apnoea (AHI less than 15)

Discussion:- This is a preliminary study of patients with open angle glaucoma to show that 67.6%(total of moderately severe and severe groups)had significant sleep apnoea.

Sleep apnoea is being more and more recognised as a risk factor in open angle glaucoma. Treatment of sleep apnoea also treats glaucoma and arrests progression especially normal tension glaucoma and hence all glaucoma patients should be screened for sleep apnoea.

Introduction

Sleep apnoea is a potentially serious sleep disorder in which breathing repeatedly stops and starts during sleep..

While a number of risk factors associated with the development of glaucomatous optic neuropathy have been identified, the aetiology of this condition remains unclear. Sleep apnoea has been implicated as a possible risk factor for the development of open angle glaucoma1 and normal tension glaucoma2. It has been suggested that repeated intermittent periods of hypopnea may imfluence the development of ganglion cell loss2.

While a consecutive case series of normal tension glaucoma patients3 and a separate series of patients with open angle glaucoma4 have suggested a higher prevalence of sleep disorders than expected in the general population, few case control studies have been performed2, 5.

Methods:- 34 patients with primary open angle glaucoma ,28 POAG and 6 NTG cases underwent overnight polysomnogram in a sleep lab.Angle closure glaucomas and secondary glaucomas were excluded from the study. This test records the patient’s blood-oxygen level, breathing rate, brain waves, and heart rate, in addition to the patient’s leg movements and eye movements as they sleep. As the patient slept, the following were monitored:

• Brain waves

• Heart rate

• Blood oxygen level

• Limb movement

• Eye movements

• Breathing pattern

• Body position

• Snoring and other noises the patient makes while sleeping

The diagnostic criteria for glaucoma included applanation tonometry, disc evaluations, gonioscopy and -Humphrey 24-2 visual fields.General conditions like hypertension cardiac disease, diabetes, cerebrovascular disease,dyslipidaemia were noted but not taken into account for the study purpose. The apnea-hypopnea index (AHI) is an index of severity that combines apnoeas and hypopneas. Combining them both gave an overall severity of sleep apnea including sleep disruptions and desaturations (a low level of oxygen in the blood). The aponea-hypopnea index, is calculated by dividing the number of apnoeas and hypopneas by the number of hours of sleep. (AHI values were categorized as 5-15 Mild, 15-30 Moderate, and above 30 listed as Severe sleep apnoea as set by the American academy of sleep medicine

Results

Out of a total 34 number of POAG patients studied,28 were POAG and 6 were NTG.An equal no of males and females (17 each)ratio was seen.The mean age of the patients was64.14. The mean IOP was 22.23mm of Hg..10 of these were found to have severe sleep apnoea with AHI of more than 30 (29.41%), 13 had moderately severe sleep apnoea (38.23%) and the remaining 11 had only a mild grade of sleep apnoea.(32.35%) 2 of the 34 who were categorised into the mild sleep apnoea group had a significant central component.

Address for Correspondance: Dr. Ravi Menon, Manavaseva Hospital, Vilangan Hills, Thrissur

351

Discussion

This study has demonstrated that a 67.6% of patients with glaucoma have significant sleep apnoea syndrome.

Almost all of us stop breathing during sleep but some tend to do so more often. Sleep apnoea is a potentially serious sleep disorder in which breathing repeatedly stops and starts during sleep. The most common kind of sleep apnoea is called Obstructive Sleep Apnoea Syndrome. It is characterized by repetitive episodes of upper airway obstruction that occur during sleep, usually associated with a reduction in blood oxygen saturation. In other words, the airway becomes obstructed at several possible sites. The upper airway can be obstructed by excess tissue in the airway, large tonsils, a large tongue and usually includes the airway muscles relaxing and collapsing when asleep. Another site of obstruction can be the nasal passages. Sometimes the structure of the jaw and airway can be a factor in sleep apnoea. There are only a few studies showing a positive association between sleep apnoea and POAG4,5,6 and NTG3 and no studies from India have been reported

OSA has been identfied as an independent risk factor for the development of high blood pressure7. Each apnoea event per hour of sleep adds about 1% to the risk of having hypertension7.

People with OSA face several health challenges – at worst they are at risk of dying of oxygen deprivation when breathing stops or slows during sleep. OSA can contribute to high blood pressure, diabetes, obesity and other systemic problems.

In the eye, prevalence of glaucoma in patients with obstructive sleep apnoea is an estimated 27%8. On the other hand our study has shown that 67.6% of glaucoma patients have significant sleep apnoea.

Because of the vascular consequences of OSA many ophthalmic manifestations exist. Non arteritic optic neuropathy has an increased incidence in people with OSA9. People with OSA may also have a higher incidence of papilledema10 .

Conclusions

This ,to the best knowledge of the authors, is the first study to show the prevalence of sleep apnoea in patients with open angle glaucoma in the Indian population and shows a staggering no of glaucoma patients have significant obstructive sleep apnoea.

About one in 10 middle aged people suffer from sleep apnoea and this is an underdiagnosed risk factor for POAG and hence all patients with POAG have to be screened for sleep apnoea. Treatment of sleep apnoea also treats glaucoma and arrests progression especially in NTG.10

Acknowledgement

1. Dr Hakkim ,managing Director of Mother hospital

2. Maneetha Sujith for the secretarial assistance.

References1. Mojon D S, Hess C W, Goldblum D. et al High prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology 1999. 1061009–1012.2. Marcus D M, Costarides A P, Gokhale P. et al Sleep disorders: a risk factor for normal‐tension glaucoma? J Glaucoma 2001. 10177–183. 3. Mojon D S, Hess C W, Goldblum D. et al Normal‐tension glaucoma is associated with sleep apnea syndrome. Ophthalmologica 2002. 216180–184. 4. Mojon D S, Hess C W, Goldblum D. et al Primary open‐angle glaucoma is associated with sleep apnea syndrome. Ophthalmologica 2000. 214115–118. 5. Onen S H, Mouriaux F, Berramdane L. et al High prevalence of sleep‐disordered breathing in patients with primary open‐angle glaucoma. Acta Ophthalmol Scand 2000. 78638–641. 6. Pearson J. Glaucoma in patients with sleep apnea. Ophthalmology 2000. 107816–817. 7. Peretz Lavie, Paula Herer. obstructive sleep apnea syndrome as a risk factor for hypertension:population study BMJ 2000;32;479.8. Kremmer. S., selbach JM, Eye 22, 1105-1109, September 2008 doi; 10, 1038/sj.eye.9. Raed Behbehani. Michaela K Mathews, Am J ophthalmol 2005:139; 3: 518-52110. Kawasaki MD; Robert D, Arch ophthalmol 2000; 118;1626-1630

Table 1

No.34

POAG28

NTG6

Mean Age64.14

Mean IOP 22.23mmhg

Mild OSA 11(32.35%)

ModeratelysevereOSA13(38.23%)

SevereOSA10(29.41%)

Rani Menon-Brief Communication

352

Introduction

Iridocorneal endothelial syndrome is a rare disease with a prevalence of less than one per two lakh population. Although associated with distinctive clinical features, 68% cases are misdiagnosed initially. [1] Prevalence of glaucoma associated with ICE ranges from 46-82%.[2] We are presenting this rare cause of glaucoma because of its diagnostic and therapeutic challenges.

Case Report

A 45 year old previously healthy woman presented with one month history of blurring of vision and pain in right eye. There was no history of coloured haloes, photophobia or trauma. At the time of presentation her best corrected visual acuity was 3m counting figures OD and 6/6 OS.

Slit lamp examination showed corneal oedema with aqueous flare. Intraocular pressure of right eye was 45mm Hg. She was started on oral and topical antiglaucoma medications. Her IOP got reduced to 25mm Hg and visual acuity improved to 6/9.When corneal oedema was reduced, slit lamp examination showed hammered silver appearance of corneal endothelium, few black iris nodules superonasally and corectopia towards 10’clock (Fig. 1, 2&3).

Fundus examination showed cd ratio of 0.7OD & 0.4 0S.Field examination showed superior arcuate scotoma OD (Fig.4). Gonioscopy showed peripheral anterior synechiae from 10-11’o clock with grade 2 angles in all other quadrants. Left eye was normal (Fig.5). Specular microscopy showed decreased cell count, polymegathism and dark cells with light central spot and light periphery. Margins of the cells were not clear. These were suggestive of ICE (Fig.6&7). OCT showed superior field depression in TSNIT graph and loss of double hump pattern right eye (Fig.8&9). With the clinical presentation and investigation, we came to a diagnosis of iridocorneal endothelial syndrome [Cogan Reese type].

Topical anti glaucoma medications- timolol and brimonidine were given. Even with topical and systemic medications IOP remained high. So augmented trabeculectomy was done. IOP returned to normal and vision was 6/9.

Discussion

ICE is a spectrum of disease characterized by primary corneal endothelial abnormality. Typically a unilateral condition although sub clinical abnormalities may be seen in other eye.[1] Usually it is seen in middle aged adult and have a female

predilection. There is no systemic or genetic association. Three main variants are progressive iris atrophy, Cogan Reese syndrome and Chandler’s. Cogan Reese is the commonest type in Orientals. [3]

Corneal endothelial changes are typical having a hammered silver appearance. Specular microscopy will show characteristic ICE cells. [Dark cells except for a light central spot and light peripheral zone]. Clear hexagonal margins will be lost. Associated features are pleomorphism and decreased cell count.[1] Corneal changes are predominantly seen in Chandler’s. In Chandler’s corneal oedema can persist even after controlling IOP.

Iris changes are more in progressive iris atrophy. Iris atrophy is more on the side opposite to pupillary distortion. Corectopia is always towards a prominent PAS. There will be ectropion uvea and iris holes [stretch holes or melting holes] .In Cogan Reese pedunculated iris nodules are seen. These nodules are normal iris tissue pinched by contracting endothelial membrane.

Glaucoma and corneal decompensation are serious sequelae of ICE. Glaucoma can be due to extensive PAS or obstruction of anterior chamber angle by membrane. Prevalence of glaucoma is 46-82%.[2] Younger patients are more affected.[2]

Aetiology is unknown. Viral [Herpes] aetiolgy is the most commonly accepted theory. Campbell and associates proposed a membrane theory according to which abnormality of corneal endothelium is the primary defect. [1]

Primary aim of the treatment is to reduce corneal oedema and glaucoma. Control of corneal oedema can be achieved by lowering IOP and by using hypertonic saline and soft contact lens. Persistence of corneal oedema can lead to corneal decompensation and keratoplasty.

Glaucoma in early stages can be controlled by aqueous suppressants. Miotics are not effective due to obstruction of trabecular meshwork. Long term medical management is usually ineffective. [2] When no longer controlled medically, surgery is indicated, of which better options are augmented trabeculectomy and shunt surgeries. Surgical procedures have variable success rate. Late failure can occur due to obstruction of fistula by synechiae or by endothelialization .Failure can occur due to inflammatory response also. Failure rate is high in young individuals.

BriefReport

Iridocorneal Endothelial Syndrome: A Case Report

Bindu N, MS, Shimna Iqbal MS.

Address for Correspondance: Regional Institute of Ophthalmology, Medical College. P.O, Calicut

353

Summary

Though uncommon in routine practice, ICE syndrome has attracted much attention both for the enigma in its pathogenesis and challenges in its diagnosis and treatment. Failure rate of medical treatment is more than 70%. So it is better to intervene surgically as early as possible. But there is a high chance of failure even after surgery. We presented this case for its rarity and management difficulties.

References1. Shield’s textbook of Glaucoma, 4th edition, 226-2362. Laganowsky H, Kerr-Muir, Hitchings KA. Glaucoma and Iridocorneal endothelial syndrome. Arch Ophthalmol. 1992; 110:346-350.3. Teekhasaenee C, Ritch R. Iridocorneal endothelial syndrome in Thai patients. Arch Ophthalmol. 2000; 18:187-192.4. Gupta V, Randhir Kumar, Gupta R et al. Bilateral ICE in a young girl with Down’s syndrome. Ind J Ophthalmol. 2009; 57:61-63.5. Chandler PA. Atrophy of stroma of the Iris, endothelial dystrophy, corneal oedema and glaucoma. Am J Ophthalmol. 1956; 41:6076. Zhang M, Chen MJ, Liang L et al. Ultrasound biomicroscopy of Chinese eyes with iridocorneal endothelial syndrome. Br J Ophthalmol. 2006;1 : 64-69

OD OS

Figure 1 : Corectopia towards 10’O clock

Figure 2&3 : Slit lamp showing hammered-silver appearance

Figure 4 : Superior Arcuate Scotoma

Figure 5 : Gonioscopy showing peripheral anterior synechiae

towards 10-11’0 clock

Figure 6&7 : Specular microscopy Right eye ICE cells

Figure 8&9 : Superior field depression in TSNIT graph

Brief Report

355

BriefReport

Kearns-Sayre Syndrome : A rare neuromuscular cause of ocular

motility disorder- A Case Report Bindu N, MS, Merin George

Address for Correspondance: Regional Institute of Ophthalmology, Medical College. P.O, Calicut

Introduction

Muscular disorders of mitochondrial etiology are not so uncommon, but less well recognized. Among the mitochondrial cytopathies of ocular significance, the most commonly encountered entities are the isolated Chronic Progressive External Ophthalmoplegia (CPEO) and the Kearns-Sayre syndrome(KSS), which are termed ‘ophthalmoplegia plus’ because of the progressive nature of ophthalmoplegia. Kearns-Sayre syndrome, though primarily a myopathy, is actually a CNS syndrome with frequent neuromuscular findings of peripheral neuropathy, ataxia,spasticity, deafness, retinopathy, optic atrophy and dementia. The condition is characterized by it’s onset prior to age 15, presence of chronic progressive external ophthalmoplegia,pigmentary retinopathy and one among the following : - Heart Block, Cerebellar defects or a CSF protein of over 100 mg/dL. Here we present a case of an incomplete form of KSS, which may evolve into a complete form.

Case Report

A 12 year old boy presented with progressive drooping of his upper eyelids. On detailed probing into the history,there was no diurnal variation for the ptosis and he had associated night blindness also. He was the second child of a non-consanguinous marriage, whose birth, growth and development had been normal. His parents and siblings were healthy.

On our preliminary examination, there was ptosis, with a levator function of 1 mm both eyes, external ophthalmoplegia affecting all movements of the eyes and a chin lift. There were no signs of vitamin A deficiency. The anterior segment examination was within normal limits including the pupils and the visual acuity was 6/6 both eyes. General examination revealed short stature and an accessory thumb in his left hand. He had normal intelligence and on detailed CNS examination, the muscle power, tone and reflexes were normal along with a normal skull and spine. The cardiovascular and gastrointestinal systems also appeared to be normal.

It was during the fundus evaluation that we suspected KSS since he had an unusual pigment mottling of the retina, especially of the posterior pole ,with absence of bone spicules. Disc and vessels appeared normal. Patient was sent to cardiology to rule out any cardiac conduction problems and to neuromedicine to pick up any additional neurological finding, if present.

The results were : The Complete Blood Count, S. Lactate & S. Pyruvate - Normal, The Blood sugar & Thyroid Function Tests - Normal, The ECG& Echocardiogram - Normal. The Pure Tone Audiogram showed no sensoryneural hearing loss and The MRI Brain & Orbit showed normal study. A Muscle Biopsy was not done.

But even with the investigation part as normal, with the clinical findings alone, we were strongly in favour of KSS since the child was as young as 12 years and the fact that the complete array of clinical signs are present only by about 20 years of age. And though the diagnosis was enthusiastically made, we could not do much in terms of treatment, except for the bilateral frontalis sling surgery which we did for his ptosis.

Discussion

Kearns-Sayre syndrome was recognized as a clinical entity in 1958 when Kearns & Sayre described the classic triad of Progressive External Ophthalmoplegia; atypical RP & complete heart block in one patient. It’s primarily a mitochondrial cytopathy of sporadic incidence, attributed to large scale deletions in mitochondrial DNA, leading to a disruption in the morphology and function of mitochondria. This results in defects in pyruvate utilization, oxidative phosphorylation and respiratory chain function. The mitochondrial myopathies are the most important cause for ‘progressive’ ophthalmoplegia; the others being Muscular dystrophies and vitamin E deficiency. A higher concentration of mitochondria in the extraocular muscles than in other skeletal muscles accounts for the predominance of ocular motility problems in this disease. There is an entity of Isolated CPEO apart from the KSS; with absence of systemic features. Identical skeletal muscle mitochondrial DNA deletions have been found in KSS and Isolated CPEO suggesting that they are the same disease; only difference being that in Isolated CPEO, deletion is found only in the muscle tissue.

Multiple organ systems are affected in KSS, predominantly the CNS, skeletal muscle & heart. It’s characterized by the obligatory triad of : onset before age 20; pigmentary retinopathy & PEO. In addition at least one of the following features are seen: cardiac conduction block, CSF protein>100 mg/dl,cerebellar ataxia.

The cardiac conduction defects and arrhythmia can occur at any time during the disease course. Endocrine disturbances which are associated include diabetes mellitus, hypothyroidism, hypoparathyroidism, growth retardation and short stature; and hypogonadism, all due to the


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respective hormonal’s deficiencies.

Investigations may show elevated S. pyruvate and lactate levels as a result of increased anaerobic metabolism. Muscle Biopsy stained with Gomori trichome stain shows a dark red color of muscle fibres, (hence called ‘ragged red fibres’) due to the high ratios of mutated mitochondria containing inclusions.

The management aspect of this classic neuromuscular disorder is disappointing. Ubiquinone or CoE Q10 which is essential for the normal mitochondrial respiration may be tried. Though it may improve the cardiac function and exercise tolerance; it has no effect on ophthalmoplegia, ptosis or pigmentary retinopathy. Thiamine, Folic acid & L-carnitine have been tried to improve the metabolic failure. But a pacemaker insertion is important if a conduction deficit is present which will prevent the occurrence of sudden death. From the ophthalmologic side,the only management procedures are ; a muscle surgery for strabismus and a sling surgery for ptosis.

Conclusion

Kearns-Sayre syndrome is only one among the rare systemic disorders whose predominant manifestations pertain to the eye. Many systemic syndromes may go unnoticed if a complete ocular evaluation and systemic work up are not done, particularly in the paediatric population . A detailed history is also as important as a systemic work up. When people present with PEO, it’s very important to do a dilated fundus examination and an associated heart block is to be ruled out along with elaborate laboratory investigations to support the diagnosis.

References1. Mark S. Borchert, Diseases of Ocular muscles – Albert & Jakobiec’s

Principles and Practice of Ophthalmology, 3rd Ed, Vol 3,Section 14,

Chapter 294, Saunders.

2. John H. Menkes,Textbook of Child Neurology, 5th Ed, Williams &

Wilkins.

3. Kenneth F. Swaiman, Paediatric Neurology, Principles and

Practice, 4th Ed, Vol 2,Mosby.

4. Richard M. Rubin and Alfredo A. Sadun, Ocular Myopathies –

Myron Yanoff & Jay S. Duker Ophthalmology, 3rd Ed, Section 3,

Chapter 9.17, Mosby.

5. Walter G. Bradley, Neurology in clinical practice, The Neurological

disorders, 4th Ed, Vol 2,Butterworth & Heineman.

6. John R. Bach, Management of patients with Neuromuscular

diseases, 2004,Hanley & Belfus.

Figure 1 : Primary position

Figure 2 : Elevation

Figure 3 : Dextroversion

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Figure 4 : Levoversion

Figure 5 : Fundus picture 1

Figure 6 : Fundus picture 2 Figure 9 : Child following bilateralsling surgery for ptosis



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Systemicdiseases & eye

Intensive Glucose Control:The UKPDS and the DCCT Revisited

Unnikrishnan AG MD, DM

Address for Correspondance: Professor of Endocrinology, Amrita Institute, Cochin.

Introduction

Diabetes is a disease characterized by chronic hyperglycemia. Thus, it is logical to presume that tight control of blood glucose levels could tackle diabetes-related vascular complications. However, this remained a presumption till the publication of two landmark studies: the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS). These two studies provided compelling evidence that glycemic control can prevent the onset and progression of diabetic microvascular complications like neuropathy, nephropathy and retinopathy. This article will focus on important research into the issue of glycemic control in diabetes, as diabetes is a disease characterized by hyperglycemia. Recently, the results of the follow up arm of the DCCT and the UKPDS have been published, and that too will be featured in this article.

Revisiting the UKPDS and the DCCT Studies

The DCCT studied type 1 diabetes, while the UKPDS was carried out in type 2 diabetes. Thus the DCCT randomized patients into intensive or conventional insulin therapy, while the UKPDS used oral drugs and insulin in a stepwise manner in conventional as well as intensive treatment arms. The DCCT studied 1441 subjects with type1 diabetes, randomized patients to receive either intensive or conventional glucose control, and followed them up for about 6.5 years. The UKPDS randomized 3867 patients to receive either intensive or conventional glucose control, and followed them up for 10 years. The reduction in hyperglycemia, as measured by the HbA1c was diff erent in the two studies. In the DCCT, the HbA1c was 7.2 % in the intensive arm and 9.1% in the

Table. Summarizing the UKPDS and the DCCT Studies

conventional arm. In the UKPDS, these values were 7% and 7.9% respectively. Thus the UKPDS studied a larger number of patients for a longer duration. However, intensive therapy could reduce the HbA1c better in the DCCT study.

How much did intensive glycemic control improve microvascular disease?

Both the UKPDS and the DCCT showed that tight glucose control can prevent the onset and progression of microvascular complications like neuropathy, nephropathy and retinopathy to a very signifi cant extent. For example, here is a discussion on diabetic retinopathy: in the DCCT, intensive therapy prevented onset of retinopathy by 76%. In addition, the progression of retinopathy was prevented by 54%, risk of maculopathy was reduced by 23% and the risk of severe non-proliferative diabetic retinopathy (non-PDR) and PDR was reduced by 47%. As noted above, the HbA1c reductions in the UKPDS were less substantial than those in the DCCT. However, the UKPDS too showed that glycemic control would reduce the onset and progression of diabetic retinopathy in type 2 diabetes. In the UKPDS, all microvascular events were reduced by 25%, risk of retinal photocoagulation was reduced by 29%, vitreous hemorrhage was reduced by 23% and the occurrence of legal blindness reduced by 16%. Interestingly, in the UKPDS Study, intensive therapy even reduced the need for cataract extraction.

Does intensive insulin therapy result in side eff ects?

In both the UKPDS and the DCCT, intensive glucose control resulted in greater hypoglycemia. For instance, there were 43 extra episodes of hypoglycemia requiring assistance per 100

*Note that in the follow up arm of the DCCT and UKPDS, macrovascular complications / cardiovascular event rates improved, showing a long term benefi t of glucose control.


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patient years. Weight gain was present in 3.4 more cases per 100 patient years in the DCCT study.

Does glucose control initially worsen retinopathy?

The DCCT clearly suggested that an “early worsening” of diabetic retinopathy can occur in subjects instituted on tight glycemic control. This early worsening of retinopathy was defined as a minimum 3-step progression of the severity of retinopathy, the new occurrence of cotton wool spots and/or intraretinal microvascular abnormalities, and retinopathy was termed as “clinically important retinopathy” in the DCCT if it occurred between baseline and the 12-month follow-up visit. In the intensive arm, early worsening of retinopathy was documented in 13.1% of 711 patients, while only 7.6% of 728 patients assigned to conventional treatment developed this deterioration. Remarkably, after 18 months, this early worsening in retinopathy reversed significantly. Eventually patients in the intensive-therapy arm fared better than those on conventional therapy. Importantly, identifiable risk factors for early worsening were higher baseline HbA1c levels and reduction of this level during the first 6 months following randomization.

What are the recent follow up DCCT/ UKPDS cohort results?

After the DCCT study was completed, this cohort was followed up in what was termed the EDIC Study (Epidemiology of Diabetes Complications and its Interventions). The follow up showed that the glucose control in the intensive group had worsened somewhat. Also, glucose control in the conventional therapy had improved. As a result the HbA1c values were comparable in the two groups after the study was stopped. However, subjects who had been randomized to receive intensive insulin therapy (in the past) had lower prevalence of retinopathy as well as other diabetic complications (including, macrovascular disease/ cardiovascular events). This suggested that even a transient period of intensive glucose control (in the distant past) might still have benefits on diabetic complications even if such an intensive therapy is stepped down.

The follow up results of the UKPDS have been published recently. The results show that intensive glucose control became more lax after the study ended, while the treatment of the conventional group became more intense after the end of the study period. In other words, after this study on type 2 diabetes ended, the intensive group slowly increased its A1C levels and the conventional group slowly reduced its A1C levels. But remarkably, people who had been on intensive therapy still did better even 10 years after the study ended. The authors attribute this to the “legacy effect” of hyperglycemia. The term “legacy effect” signifies that even a short period of glucose control (in the distant past) will have benefits in the remote future, even if glucose control

has become a little lax after the period of tight control. Unlike glycemic control, blood pressure control does not seem to have a legacy effect, but a rather more immediate/ short term benefit in type 2 diabetes. Indeed, glycemic control started early and continued can, in the long term, even prevent cardiovascular events, as shown by the new UKPDS data.

Did the UKPDS studies give any insight into the natural history of diabetes?

The UKPDS showed that type 2 diabetes is a progressive disease. Over a period of time i.e. the 10-year study duration, the HbA1c levels tended to rise. This progression in the diabetic state was also attributable to failing beta cell function. The clinical implication is that a stepwise escalation of oral drugs and eventually insulin will be required to prevent unnecessary exposure of the patient’s tissues to hyperglycemia.

What was the effect of blood pressure lowering on diabetic complications?

The UKPDS showed that blood pressure control can favorably impact microvascular and macrovascular complications. The UKPDS randomized 1,148 subjects with hypertension in addition to their type 2 diabetes to receive either of the following 2 regimens: a less tight blood pressure (BP) control regimen or a tight blood pressure control regimen. The less-tight BP control and the tight group achieved mean blood pressure readings of 154/87 mm Hg and 144/82 mm Hg respectively over a median duration of 8.4 years. The tight BP control regimen reduced microvascular endpoints by 37% (p=0.0092), risk of any diabetes-related endpoint by 24% (p=0.0046), and stroke by 44% (p=0.0013). Tight BP control even reduced the prevalence of deterioration of visual acuity by 47% (p=0.0036). This suggested that tight BP control resulted in less diabetic maculopathy. Thus the UKPDS study definitely suggests that blood pressure control is important in tackling diabetic retinopathy.

What is the recent controversy on target HbA1c?

The last year saw the publication of the ACCORD study, which showed an increase in cardiovascular death in subjects on intensive control. While a similar study called ADVANCE (with significant differences too) study showed no significant cardiovascular risk, the issue of glucose control has become a matter of debate. This is especially true after a third study, called the VADT study showed that very intensive glucose control can have no significant benefits on cardiovascular mortality. It is increasingly being known that hypoglycemia can adversely affect cardiac events, and it is obvious that tighter the control is, more is the risk of hypoglycemia. Thus, it is the author’s opinion that in subjects who are older, have longstanding diabetes and significant risk factors for cardiovascular risk, very aggressive glucose control may

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Unnikrishnan A.G. - Intensive glucose control

not benefit, and may even increase cardiovascular risk. In younger subjects, with recent onset diabetes and few or no cardiovascular risk factors, strict glucose control started early on could prove beneficial in the long run. What then, is the ideal A1C to aim for ? Again, in the author’s opinion, the American Diabetes Association-recommended target of <7% seems more reasonable compared with the stricter recommended by other reports.

References

1. Holman, R.R., et al., 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. NEJM 2008:1577-1589.

2. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-986.

3. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352:837-853.

4. The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial. Arch Ophthalmol. 1995; 113:36-51.

5. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and

Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med. 2000; 342:381-389.

6. Skyler, J.S., et al., Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials: A Position Statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. 2009:298-304.

7. UK Prospective Diabetes Study. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ, 1998. 317(7160):703-713.

8. Chalmers, J. and M.E. Cooper, UKPDS and the Legacy Effect. NEJM 2008:1618-1620.

9. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research, G., Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes. NEJM 2005:2643-2653.

10. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research, G., Retinopathy and Nephropathy in Patients with Type 1 Diabetes Four Years after a Trial of Intensive Therapy. NEJM 2000:381-389.

11. The Action to Control Cardiovascular Risk in Diabetes Study, G., Effects of Intensive Glucose Lowering in Type 2 Diabetes. NEJM 2008:2545-2559.

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Address for Correspondance: Uma Eye Clinic, Anna Nagar, Chennai – 40

News thatyou can use

Testing the Calibration of A Goldman Applanation Tonometer

M. Chockalingam DNB FRCS (Glasgow) PGDHM, N. V. Arulmozhivarman MS

The accuracy of the intraocular pressure measurements obtained with the Goldman Applanation tonometer critically depends on the accurate calibration of the tonometer used. It is mandatory to check the calibration of applanation tonometer at least twice a year. The Goldman Applanation tonometer has (1) The calibration rod comprising of the control or check weight and weight holder to which it is fixed is provided separately with the Goldman Applanation Tonometer (Figure 1) (2) The axis of the tonometer which the control weight is attached to the holder (Figure 2). The holder and the weight fixed on to the axis of the tonometer are shown in Figure 3. The control weight on the calibration rod has five circles engraved on it. The central mark corresponds to 0 on the dial position, the first markings on either side on 0 correspond to 2 on the dial position and the last markings on either side of 0 correspond to 6 on the dial position.

Figure 1 – Calibration Rod With Control Weight And Holder

Figure 2 – Axis Of The Tonometer

Figure 3 – Holder and Weight on the axis of the Tonometer

Step By Step Approach To Test Calibration Of Goldman Applanation Tonometer The calibration is tested in three positions of the weight on the calibration rod namely 0, 2 and 6 at the corresponding dial positions.

First Step The first step in testing the calibration of Goldman Applanation Tonometer may be done with or without fixing the calibration rod since it is done at dial position 0. The steps to be followed are – (1) Set the tonometer in position on the slit – lamp stand with the bi – prism head in place and the tension on the circular dial on the right side as seen from the examiner’s side of the slit - lamp(2) Slowly twirl the circular dial counter – clockwise until the head rocks back towards you. The tension on the circular dial should read between 0 – 2 mm Hg below zero (Figure 4)(3) Slowly twirl the circular dial clockwise until the head rocks forwards away from you. The tension on the circular dial should read between 0 – 2 mm Hg (Figure 5)

Figure 4 – Movement of the circular dial in the counter – clockwise direction or backwards at dial position 0

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Second Step

This is the most important step to check calibration of Goldman Applanation Tonometer since measuring of the intraocular pressure in this area is highly significant. For this step, the control weight is used. One of the marks on the weight corresponding to drum position 2 is set precisely on the index mark of the weight holder. The control weight and the weight holder are fitted over the axis of the tonometer so that the longer part of the weight points towards the examiner (Figure 5)

Figure 5 – Checking calibration errors at dial position 2

(1) Slowly twirl the circular dial counter – clockwise or backwards (Figure 6) until the head rocks back towards you. The tension on the circular dial should read between 17 – 20 mm Hg below zero.(2) Slowly twirl the circular dial clockwise (Figure 7) until the head rocks forwards away from you. The tension on the circular dial should read between 20 – 23 mm Hg.


Figure 7 – Movement of the circular dial in the clockwise direction or forwards at dial position 2

Third Step

One of the marks on the weight corresponding to drum position 6 is set precisely on the index mark of the weight holder. The control weight and the weight holder are fitted over the axis of the tonometer so that the longer part of the weight points towards the examiner (figure 8) (1) Slowly twirl the circular dial counter – clockwise until the head rocks back towards you (Figure 9). The tension on the circular dial should read between 56 – 60 mm Hg below zero. (2) Slowly twirl the circular dial clockwise until the head rocks forwards away from you (Figure 10). The tension on the circular dial should read between 60 – 64 mm Hg.

Figure 8 – Checking calibration errors at dial position 6

Chockalingam - Calibration of a Goldman AT


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Examples of errors in measurement of intraocular pressure

If the error of measurement is 2 mm Hg and the intraocular pressure recorded with the tonometer is 12 mm Hg then the actual range of measurement is between 10 and 14 mm Hg.

The points tested should bracket the threshold levels evenly – higher the level being tested, the greater the interval is likely to be. If the tonometer is inaccurate at any of these dial positions, it should be returned to the manufacturer for recalibration.

Reference(1) Measurement of Intraocular pressure, Garway – Heath DF et al. World Glaucoma Association Intraocular pressure – Consensus Series 4. The Hague. The Netherlands(2) Asia Pacific Glaucoma Guidelines, 2nd Edition, South East Asia Glaucoma Interest Group, 2008.

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His father urged him to do something more practical. He therefore studied medicine at the German university in Prague, the Karls-Universität, graduating in 1923. That year he also obtained is medical doctorate.

From 1919 to 1924 Goldmann was assistant to Professor Armin Tschermak von Seyseneck (1870-1952) in the physiologic institute. At the physiological institute in Prague Goldmann developed a life-long interest in optics, physics, and instruments. His major contribution to ophthalmology was in the development and refinement of instruments, including the slit lamp, colorimeter, bowl perimeter, applanation tonometer, gonioprisms, dark adaptometer, and fluorophotometer. These were developed in cooperation with the company Haag-Streit AG.The construction of a new slit-lamp,the Haag-Streit 360 in 1933, later the Haag-Streit slit-lamp 900, which is still the world standard, then publication of the Basics of exact perimetry together with the introduction of the Goldmann perimeter in 1945, which set the standard for at least 40 years in perimetry until automated perimetry became used in daily practice. His work on biomicroscopy of the chamber angle, of the central and peripheral fundus, and of the vitreous with the gonioscopic, the three mirror Goldmann, and the ‘macula’ lenses in 1949, and the introduction of the applanation tonometer in 1956 provided the essential tools for the daily work of ophthalmologists around the world. In Prague he was also the assistant of the ophthalmologist Anton Elschnig (1863-1939). In 1924 he came to the eye clinic in Bern as an assistant under August Siegrist (1865-1947). In 1927 he was appointed Oberarzt and in 1930 Privatdozent at the clinic.

He was trained by von Tchermak-Seysenegg and Elschnig in

Prague, then by Siegrist in Berne.In 1935 Goldmann married Erna Renfer and that year succeeded Siegrist as director of the clinic and professor of ophthalmology. He was granted Swiss citizenship 1936& in 1976 from the University of Geneva.

He was an exceptionally great teacher for the students &dean of the faculty 1945 to 1947 and He became Rector magnificus of the University of Berne in 1965.He was certainly, for almost half a century, one of the world’s experts in glaucoma. He was not only a scientist, but also a caring and beloved doctor of his patients. Hans Goldmann’s lectures to the students were the highlights of the curriculum of Berne. Being the inspiring teacher, he trained the majority of departmentheads and professors of ophthalmology in Switzerland, such as R Witmer, A Bangerter, Niesel, F Fankhauser, G Eisner, G Schmitt, and also had some ophthalmic grandchildren, such as J Flammer, F Korner, and Balder P Gloor.He retired in 1968 having chaired the department for 44 years.After retiring in 1968 Goldmann still continued research until his eighties. Standing out among his many experiments,observations, and inventions are his work on cataract formation and on determination of the volume of production of the aqueous, his critical evaluation of tonography, his instrument for objective determination of visual acuity, the slit-lamp fluorophotometer, the instrumentation for cell count in the anteriorchamber, and finally that for stereochronoscopy of the optic nerve head.

Hans Goldmann never gave a paper on the same subject twice. His personal library, contained on shelves which ran from floor to ceiling, adorned most of the numerous rooms in his lovely Berne home. He remained active in research until his late eighties. he suffered in his lastyears from many illnesses. When, after a period of illness he could not present anything new, he refused to give the Fuchs Lecture in Vienna when he was about 70 years old. Later, he could still give the Aschoff Memorial Lecture.He received the Vogt Prize, was the first continental European to receive the Proctor medal, was awarded the Gullstrand, Gonin,Donders, and Graefe medals, and gave the Doyne, Montgomery, Arthur Bedell, and Proctor lectures in1991 ophthalmology lost one of greatest genius.

OphthalmicHistoryGoldmann

Compiled by: Dr. Koteshwar Rao, Giridhar Eye Institute, Cochin - 20.

Goldmann, a most gifted fascinating personality, born in Komotau in Bohemia, grew up in Prague.He has demonstrated great skill in mathematics and science early in life. He had incredibly broad interests and an amazingly keen intellect. He attended the Gymnasium in Komotau and decided to become an astronomer.

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Compiled by Dr Savita Bhat, Giridhar Eye Institute, Kochi

JournalReview

Angle Closure In The Andhra Pradesh Eye Disease StudySirisha Senthil, Chandrasekhar Garudadiri et al.Ophthalmology 2010;117:1729-1735

The prevalence of primary angle closure glaucoma (PACG) reported from various states performed in South Indian population varies and the variation is basically due to different definitions of glaucoma and methodologies used. The reported prevalence was 0.5% from Aravind Comprehensive Eye Survey, 4.32% in the Vellore Eye Survey, 1.08% from Andhra Pradesh Eye Disease Study urban data and 0.88% from Chennai Glaucoma Study. In this study, the authors estimated the prevalence and associated risk factors for primary angle closure glaucoma (PACG) and primary angle closure (PAC) and primary angle closure suspect (PACS) in the Indian state of Andhra Pradesh. 3724 subjects aged ≥ 40 years were studied between 1996 and 2000 in a population based cross-sectional study. Trained professionals performed detailed eye examination including applanation tonometry, gonioscopy, 24-2 Humphrey visual fields. Angle closure was diagnosed and categorized using International Society of Geographical and Epidermiological Ophthalmic criteria. PACG was present in 35 subjects i.e. 0.94%, PAC in 0.3% and PACS in 2%. The prevalence of angle closure disease (ACD) i.e. (ACD = PACG + PAC) was 1.26%. The increasing age, increase in intraocular pressure, diabetes mellitus and female gender was significantly associated with angle closure disease. Blindness due to PACG was found to be 20%. Lower prevalence rate of PACG in this study compared to VES was explained by the different diagnostic definition used by VES for PACG. Earlier publication from APEDS by Dandona et al covered urban data that constituted 25% of the total data. In this study, the authors found no association of PACG with hyperopia (P=0.05) or with systemic hypertension (P=0.24). As this was a population based study, not all patients underwent complete ophthalmic evaluation as gonioscopy was not possible during house -visits.

High Definition Image Of Trabeculectomy Blebs Using Spectral Domain-Optical Coherence Tomography Adapted For The Anterior Segment. Singh M, See JL, et al.Clinical & experimental ophthalmology 2009;37(4)345-51

The aim of this study was to image trabeculectomy blebs using spectral domain Optical Coherence Tomography (SD-OCT). This was a prospective cross-sectional study which

included 51 patients who had undergone trabeculectomy and were followed upto 3 months. Blebs were imaged using an adapted SD- OCT system (Cirrus HD-OCT) and time domain anterior segment (AS-OCT). An observer masked clinical data assessed the utility of SD-OCT and AS-OCT in visualizing structures in useful and failed blebs. 51 eyes were imaged of which 43 i.e. 84.3% trabeculectomy were successful. SD-OCT showed wall thickening and hyperreflective areas inside the wall in a greater proportion of successful blebs than AS-OCT. SD-OCT showed the bleb activity (23.3% Vs 48.8%, P=0.02), scleral flap (34.9% v/s 90.7%, P <0.0001), sub flab 20.9% v/s 72.1%, P<0.0001) and ostium 9.3% v/s 88.4%, P <0.001) in fewer successful blebs than AS-OCT. The internal ostium was not visualized in any failed bleb using SD-OCT. However, AS-OCT showed the ostium in 87.5% failed blebs (P=0.01). SD-OCT imaging was applied to show superficial features in the bleb wall. However, the SD-OCT had limited clinical utility in that it did not provide successful information about features such as flap position, bleb cavity formation or patency of sub flab space or internal ostium. Anterior segment imaging techniques can thus help in assessing the causes of failure of trabeculectomy. Early imaging following trabeculectomy and timely intervention with wound modulators are likely to improve the surgical outcome in a failing trabeculectomy.

Bleb Morphology And Vascularity After Trabeculectomy With Intravitreal Ranibizumab : A Pilot Study.Malik Y Kahook.American Journal of Ophthalmology,2010;3:399-403

Authors investigated the outcome following trabeculectomy using intra operative intravitreal Ranibizumab and topical Mytomicin-C (MMC) v/s MMC alone. This was a prospective randomized single site pilot study in which 10 patients were randomized to either standard trabeculectomy with MMC group or trabeculectomy with intravitreal Ranibizumab and MMC (Group B). Patients with primary open angle closure were randomized 1:1 to either combination therapy using 0.5mg intravitreal Ranibizumab and topically applied MMC 0.4mg/ml for 2 minutes or same dose of MMC applied alone at the time of Trabeculectomy surgery. The primary end point measured was bleb morphology and vascularity using the Moorfield bleb grading system. Unqualified success was defined as intraocular pressure more than 5mmHg and less than 22mmHg and a 30% decrease in baseline without use of post-operative hypotensive medication. Qualified success was defined as postoperative intraocular pressure of more than 5mmHg and less than 22mmHg and

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a 30% decrease from baseline with use of postoperative hypotensive drops. All patients completed the study and were qualified as unqualified success. There were statistically significant difference in peripheral bleb areas (P = 0.02) peripheral bleb vascularity (P 0.02) and non-bleb extra peripheral conjunctival vascularity with patients in Group B exhibiting more diffuse bleb with a lower degree of

vascularity. This study concluded that with the combination of Intravitreal Ranibizumab and topical MMC at the time of Trabeculectomy resulted in more diffuse bleb with less vascularity as compared to the usage of topical MMC alone. However, further studies are planned to better question the utility of anti-VEGF agents as modulators of wound healing post trabeculectomy.

Journal Review

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PTERYGIUMA Practical Guide to managementAuthor: Alfred L Anduz, USAPublished By Jaypee Brothers Medical Publishers (p) Ltd.St. Louis (USA)First Edition 2010Pages:118 Price Rs: 1295

As the occurrence of pteryguim cases found worldwide continues to escalate, a text that addresses these cases in a functional and comprehensive way is essential to provide effective care.

Pterygium: A practical guide to Management presents a practical approach to the use and analysis of techniques involved in the clinical care of specific pterygium cases. This ground – breaking text divulges reasons for employing various methods and identifies indications and innovations for peculiar cases. Inside, you will find practical clinical techniques, preventive measures and repair of complications. It is a manual of clinical situation and deals with how to approach and set the best results.

Inside you will find • An emphasis on prevention, primary surgery, reduction of recurrence and the role of inflammation in pathogenesis and surgical results• Discussions of practical situations with preoperative treatment, intraoperative techniques, and post operative care• Case studies and indications for certain techniques • Clinical staging of pterygium with its histopathologic characteristics and early preventive therapy• Surgery sections, with appropriate regimes and established surgical techniques

Sections Include

Epidemiology, pathogenesis, pathology, prevention, surgical management, complications, unusual cases, etc...

Author’s innovative approach in analyzing and providing clinical care in pterygium cases makes Pterygium: A practical guide to management an invaluable text for practicing ophthalmologists, residents and medical students around the world. Both novice and advanced surgeons involved with the treatment of pterygium will benefit from adding this essential text to their collection.

GLAUCOMA HANDBOOKEdited by Anthony B. Litwak

BookReview

Compiled by Dr. C. V. Andrews Kakkanatt, JMMC, Trichur

Published by Butterworth HeinemannBoston, USA.First EditionPages: 365Price 65 £Detecting early glaucoma damage and deciding when to initiate treatment in the glaucoma suspect is a topic of much controversy, and although diagnosing advanced glaucomatous optic neuropathy is rarely a dilemma, managing and determining progression in patients with advanced disease often is. Many remedies and management schemes are based on anecdotal experience. This hand book is a compilation of academic literature and clinical experience. The author try to incorporate practice guidelines and clinical experience and explore other philosophies on glaucoma management so that each practitioner can make informed clinical decisions. This book is designed to be clinically oriented while incorporating the academic information that is available.

The author wanted to design a text book that clinicians could refer to on a daily basis to assist in glaucoma diagnosis and treatment decisions. This book is not intended to replace the classic academic textbooks of glaucoma; it is design to give practical clinical information and guidelines. The contributing authors are all seasoned clinicians, sharing their insights on this enigmatic disease. This book will aid students, residents and doctors to improve their diagnostic and management skills for the benefit of their glaucoma patients.

From diagnosis to follow – up to reevaluation, this hand book provides clear and practical clinical guidelines on how to best manage your glaucoma patients. With significant advances in technology and therapeutics, it is more important than ever to have a trusted source when making clinical decisions about your patients.

Dr. Litwak and his contributors bring unparalleled expertise to the understanding of this complex and difficult- to- manage disease.

Glaucoma handbook was designed for use in your daily practice –

Whether you have a question about optic nerve or visual field interpretation, setting a target pressure, need to understand potential side effects of a new therapeutic agent, or need advice on how to ensure a patient will comply with treatment.

Clinical guidelines throughout are supported by the scientific literature to provide you with the most current management schemes for glaucoma.

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SpotDiagnosis

Identify the field defect

Send your answers to: [email protected]

Exciting prizes to be wonLast issues’ spot diagnosis answer is

“Choroidal tear, vitreous haemorrhage and commotio retinae”

Winners of the September issue spot diagnosis are Dr Veena Viswam, Dr P Jeotirmayi, Dr Suma Unnikrishnan, Dr Mihir Shah, Dr Shanti Sunil, Dr Deepa C,

Collect your prize at the KJO stall during KSOS DRISHTI 2010

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PG Corner

Tonometry

Compiled by: Dr. Savitha Bhat, Giridhar Eye Institute, Cochin - 20

Tonometry, in reference to the eye, is the noninvasive measurement of intraocular pressure.

A tonometer is an instrument that exploits the physical properties of the eye to permit measurement of pressure without the need to cannulate the eye.

Tonometers in which the intraocular pressure is negligibly raised during intraocular pressure measurements, less than 5%, are termed low-displacement tonometers. Eg. Goldmann Applanation Tonometer.Mackay-Marg tonometer.

Tonometers that displace a large volume of fl uid and consequently raise intraocular pressure signifi cantly are termed high-displacement tonometers. High-displacement tonometers are less accurate. Eg.Schiotz , Maklakov.

Tonometers can be classifi ed into ;

i) Indentation tonometers

Schiotz tonometer : IOP measurement is based on volume change before and after placement. The schiotz tonometer was calibrated by

Friedenwald, based on invitro & invivo manometric studies in 1948. The scale readings are converted into IOP values from the Friendenwald nomogram.

It is easier to use during mass screenings, less accurate and variables like ocular rigidity, corneal thickness ,variable expulsion of intraocular blood etc aff ect the reading.

ii) Applanation tonometers

The Imbert-Fick principle : When a plane surface is applied to a fl exible sphere with a force (F) causing an area (A) to be fl attened, the pressure inside the sphere, Pt = F/A

2 types : Variable force & Variable area

A) Variable force type (Constant area) applanation tonometers - Contact TypeGoldmann tonometer : Considered to be the gold standard.Calibrated for 550µCCT Perkins tonometer : Hand held . Similar to Goldmann tonometer Draeger tonometer : Hand held , Similar to Perkins

Uses an optical element , a biprism.Needs fl ourescien staining.CCT correction to be made to measured IOP

Mackay-Marg tonometer : Electronically controlled plunger measures IOP ; traced on a paper strip . No optical element.

Tonometers based on Mackay-Marg

Tonopen : portable , hand held . electronic strain guage readings converted into IOP values.

Pneumotonometer : Pneumatically controlled sensing head. No plunger.

Note: Mackay-Marg type tonometers are less aff ected by corneal irregularities , as they don’t have an optical element.

Both are useful in corneal edema & scarring. Can also measure over soft / bandage contact lens.Can also measure on peripheral corneas

B) Variable force type ( Constant area ) applanation tonometers - Non-Contact Type

Air-puff tonometer ( Invented by Grolman)

Optoelectronic sensor measures light refl ected from cornea, applanated by a collimated jet of air. The time lag between various stages of applanation is converted into IOP readings. Eg: Pulsair

Advantages : No risk infection , no anaesthetic , can be used in children and for mass screening

Ocular Response Analyser

This air-puff tonometer. It can measure the Cornea Compensated IOP ( Independant of corneal thickness) , Goldmann Correlated IOP , Corneal Rigidity Factor (Correlates well with corneal CCT) and Corneal Hysterisis(Viscous damping property of cornea). Eyes with low Corneal Hysterisis are more susceptible to ONH damage from IOP fl uctuations, due to poor damping.

C) Variable area (Constant force) type applanation tonometers – Contact Type

Maklakov tonometer

The area of cornea applanated by a known force is measured. Dumbbell- shaped metal cylinders of diff erent weights are used. The diameter of the applanated area can be measured from the imprint created by the contact with instrument. IOP read from a conversion table. Displaces a large volume of


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fluid , affected by ocular rigidity . less accurate but portable.

iii) Non-applanating type , Contact tonometers

Dynamic Contour Tonometer

Measuring head matches the contour of cornea. Hence , minimal or zero applanation.The appostional force of 1gm is constant. It electronically measures IOP via a piezo-resistive sensor built into measuring head. Not affected by corneal rigidity.

Capable of continuous IOP measurement. Slitlamp mounted instrument.

Rebound tonometer

The rebound characteristics of a probe after its momentary contact with cornea , like , deceleration , contact time etc

are analysed through complex algorithms by a software to measure the IOP. No topical aneasthesia required. Its calibrated for average CCT’s like the Goldmann tonometer, hence affected of CCT . Handheld device.

Can be used in children and uncooperative adults

Disinfection of tonometers

For contact type tonometers , the risk of transmitting viral contaminants like Adenovirus , HBV , HTLV-III and other bacterial pathogen is high. Wiping with 3% Hydrogen Peroxide or 70% Isopropyl alcohol disinfects the tonometer heads.

Using disposable covers over the measuring head in Makay-Marg type tonometers can help prevent spread of pathogens.

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PG Corner

Schiotz

Draeger

Maklakov

Goldman applanation

Mackay Marg

TonopenORA

Rebound tonometer

DCT

Pulse air puff

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General Instructions to Authors

The Kerala Journal of Ophthalmology (KJO) is a quarterly; peer reviewed one, devoted to dissemination of the latest in ophthalmology to the General Ophthalmologists as well as to specialists in the various subspecialties of this discipline. It invites submission of original work dealing with clinical and laboratory materials.

Authors submitting materials to this journal are requested to adhere STRICTLY to the norms laid down below. The matter must be typed on one side of the paper. A margin of 1” must be left all around and the material must be double spaced. A page should contain not more than 25 lines. Two copies of the text in paper and one copy in a CD must be submitted to the Editor and the corresponding author is advised to keep another copy with him. The corresponding author must give it in writing in his covering letter that the same matter will not be submitted elsewhere if accepted. He must also enclose the copyright transfer of his work to this journal. The papers sent will be subjected to peer review. The accepted manuscripts become the permanent property of this journal. The author is informed that, if his work is returned to him for correction / clarification after peer review, he should effect the same and send the manuscript back to the Editor within one month. Each manuscript component mentioned here under must begin with a new page and the pages are to be numbered at the right tip corner starting from the Title page.

1. TITLE: The title of the work must be brief and precise. It should not exceed two lines and 40 characters (including comma, period) Author(s) full name (s) must be given along with his (their) degree and the affiliations. Corresponding author’s name, correct address (including e-mail and Fax, if available) and phone number must be mentioned at the bottom left hand corner of the first page.

2. ABSTRACT: The abstract is to be given in the beginning itself. It should not exceed 200 words. It must contain the aim, methodology, results and conclusion. For case report, summary / conclusion alone is to be given.

KEY WORDS: (maximum five) in capitals are to be included at the end of Abstract.

3. INTRODUCTION: Describe the aim of the study, along with the hypotheses that were tested. Only necessary references are to be given.

4. METHOD: Give in detail the materials used and the methods employed. Describe the type of study.

Instructionto Authors

Pharmacological names only must be mentioned for the drugs used and, if proprietary name is used, then the manufacturers name must be given in parentheses. Except for standard, well-accepted abbreviations (including SI Units), all others must be introduced in parentheses when the full term is used for the first time in the article.

5. RESULTS: Giver only the results obtained by the study under discussion. State the statistics in the correct scientific form (P value, mean etc). Results based on assumptions must not be given. Indicate in the text the place where the tables have to be inserted.

6. DISCUSSION: The discussion should be to the point and relevant to the subject under discussion. This section can be combined with the previous one if the author desires. Avoid speculations. Use only standard abbreviations or the abbreviations already introduced.

7. ACKNOWLEDGEMENT: This is to be made only to those who were directly and scientifically involved with the preparation of the paper. Permitting authorities, technicians, photographers who assisted in the work need not be mentioned.

8. REFERENCES: The references should be given in numerical order in which they first appear in text and not in alphabetical order (Citation Order System). It should be numbered consecutively in the text. The references will not be checked by the Editor or by the Peer reviewer and hence the author is solely responsible for its completeness and the accuracy. Period should not be employed anywhere in the references. Personal communications, unpublished data and poster references, if mentioned, should be in the text itself and the source mentioned in parentheses. References should be in the following form:

Journal reference: Author(s) full title, Journal name (as abbreviated in Index Medicus), volume number, pages and year. If there are more than three authors, then mention the first three authors and then ‘et al’.

Book reference: Author(s) (& Editor, if any), title of book (and chapter), publisher, place of publication, page number (s) of the cited portion and year.

9. THE LEGEND: The legend for the illustrations (and tables, if necessary) must be given in a separate sheet of paper and should be typed double-spaced.


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submitted.

11. All manuscripts are subjected to editorial board review.

12. Other Categories of Manuscript

a) Original Articles should generally not exceed 3,000 words or 12 double – spaced pages. b) Review Articles: can be on topics of relevance to clinical practice, research methodology, community ophthalmology or investigative work, of relevance to visual science. These articles should include up to date review of existing literature, and summarize the current status / preferred practice for that particular topic.

Brief reports are short communication of new instruments, new laboratory techniques or surgical techniques as well as interesting case reports with unique findings. These should not exceed 1000 words with a maximum of 2 illustrations. They should follow the format – introduction, case, and discussion. No more than 8 references should be cited. Each brief report must begin with a 75-100 word summary that highlights the significance of the articles.

Illustrations: The photos and figures should be prepared in glossy prints with good contrast and of the size 6” x 4”. Only salient details should be included. On the back of the illustration, the figure number in text, title of the paper, the first author’s name and the top side (marked with an arrow) must be specified. Except for arrows, no text is to be on the photos. It is the duty of the author(s) to get the patient’s written permission when the subject is identifiable in the photo. Submit two sets of illustrations. Illustrations from other Journals and books are usually not accepted. If used, it rests with the author(s) to get the copy right permission from the original author / publisher and this permission letter must be sent to the Editor at the time of submitting the manuscript. For Histological figures the stain and magnification used should be noted e.g.: H & E Stain x 70.

10. TABLE: It should be in double space. Each table must have an Arabic numeral (except for single table) and a title both in a single line. Each column in the table must have a short heading. If a table is large, then it must be continued in a second page, which also must have the table number and the title. Avoid vertical lines in the tables. Two sets must be

In the September 2009 KJO issue the name of the second author of the original article OCULAR MANIFESTATIONS OF INTRACRANIAL SPACE OCCUPYING LESIONS

is wrongly typed as DR ANJU. The second author is DR SANDHYA SOMASUNDARAN

307 - ksos · 2011. 7. 2. · m.d., 7th edition 4. atlas of glaucoma, neil t choplin, diane c...

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