PREVALENCE OF DRY EYE IN PLANNED PENETRATING OR ENDOTHELIAL KERATOPLASTY

John D. Sheppard, M.D., M.M.Sc.President, Virginia Eye Consultants, Norfolk, Virginia

Professor of Ophthalmology, Microbiology & Molecular Biology

Clinical Director, Thomas R. Lee Lab for Ocular Pharmacology

Medical Director, Lions Eye Bank of Eastern Virginia

Ophthalmology Residency Research Director

Prevalence of Dry Eye in Planned Penetrating or Endothelial Keratoplasty: Poster #15668 Abstract• Topic: Ocular Surface Disease • Keywords: Dry eye, Endothelial keratoplasty, Penetrating keratoplasty, Complications of Surgery

 • Purpose: To identify the prevalence of Dry Eye in patients undergoing either penetrating keratoplasty (PKP)

or endothelial keratoplasty (DSEK) in a large academic referral practice.

• Methods: 220 consecutive keratoplasty patients were analyzed retrospectively over a 2 year period.  Data included indication for keratoplasty, age, complaints specific to dry eye, superficial punctate keratopathy (SPK) consistent with dry eye, and ipsilateral and contralateral osmolarity.  120 PKP patients and 100 DSEK patients were accumulated.  Most common indications for PKP were Keratoconus (64), Corneal Scar (25) and Pseudophakic Bullous Keratopathy or PBK (21).  Most common indications for DSEK were Pseudophakic Fuchs Dystrophy (84), PBK (12), and Phakic Fuchs Dystrophy (4).

• Results: 54 of 120 (45%) PKP patients and 89 of 100 (89%) DSEK patients had a preoperative dry eye.  16/64 (25%) of Keratoconus, 22/25 (88%) of Corneal Scar, and 18/21 (86%) of PBK patients anticipating PKP surgery had a dry eye.  73/84 (87%) of Pseudophakic Fuchs Dystrophy, 9/12 (75%) of PBK, and 3/4 (75%) of Phakic Fuchs Dystrophy patients anticipating DSEK surgery had a dry eye.  Osmolarity above 307 mOsm/L correlated with dry eye SPK and/or symptoms in 96% of PKP patients and 93% of DSEK patients.

 • Conclusion: Although dry eye is common in patients undergoing corneal transplantation, this data is the

first comprehensive analysis addressing pre-operative prevalence.  Keratoplasty candidates should be carefully screened for dry eye and appropriate therapeutic measures should be instituted prior to keratoplasty surgery.

Dry Eye Prevalence: Surgery Candidates• Cataract Surgery1 77%• Penetrating Keratoplasty2 45%• Endothelial Keratoplasty2 89%• Lasik3 27%• Glaucoma Surgery4 78%• Blepharoplasty5 26%

1 Trattler, ASCRS CME Supplement, 2013

2 Sheppard, WCC, 2015

3 Azuma, BMC Research Notes, 2014

4 Leung, Journal of Glaucoma, 2008

5 Prischmann, JAMA Facial Plastic Surgery, 2013

Surgical Complications of Dry Eye• Irregular Astigmatism• Delayed epithelial healing• Increased infection risk• Inaccurate Biometry creating post-cataract refractive error• Post-Lasik regression• Post-Lasik neurotrophic keratopathy• Increased risk of allograft rejection• Increased risk of glaucoma filtering procedure failure• Increased risk of post-blepharoplasty dry eye pain• Cataract surgery adds 1 Delphi Panel severity step• Lasik surgery adds 2 Delphi Panel severity steps

Severity Level 1 2 3 4

Symptoms Mild to moderate Moderate to severe Severe Extremely severe

Conjunctival Signs Mild to moderate Staining Staining Scarring

Corneal Staining Mild punctate staining

Marked punctate staining; central staining; filamentary keratitis

Severe staining; corneal erosions

Other SignsTear film; decreased vision (blurring)

Treatment Options

• Patient education• Environmental

modification• Preserved tears• Control allergy

• non-preserved tears• Gels, ointments• Cyclosporine A• Topical steroids• Secretagogues• Nutritional support

• Oral tetracyclines• Punctal plugs (once

inflammation is controlled)

• Systemic anti-inflammatory therapy• Oral cyclosporine• Acetylcysteine• Moisture goggles• Surgery (punctal

cautery)

If no improvement, add level 2 treatments

If no improvement,add level 3 treatments

If no improvement, add level 4 treatments

Surgery Impacts Dry Eye

Plan pre-op and post-op care accordingly

Cataract Surgeryadds 1 severity step

LASIK adds 2 severity steps

Behrens A, et al. Cornea. 2006;25:900-907.

Most Neurodestructive Procedures:Procedure

• Penetrating Keratoplasty• Lasik, Corneal Inlay• Secondary AC IOL• Cataract with LRIs• LRIs• DSEK• Cataract, RLE or ICL• SMILE

Cord Length• 25 mm• 21 mm• 6 mm• 6 mm• 4 mm• 4 mm• 2 mm• 2 mm

Study Design• Retrospective clinical analysis• Single surgeon• 220 consecutive corneal transplant patients:

• 120 penetrating (PKP) patients• 100 endothelial keratoplasty (DSEK) patients

• Dry eye definition:• Complaints of dryness, irritation, visual fluctuations• Superficial punctate keratopathy (SPK):

• Grade II or greater NEI Scale in two zones• SPK separate from corneal micro-cystic edema (MCE)

Penetrating Keratoplasty Patients• Indication Number

Percent• Keratoconus 64 53%• Corneal Scar 25 21%• Pseudophakic Bullous Keratopathy 21 18%• Graft Failure 10 8%• Total 120 100%

Endothelial Keratoplasty Patients• Indication Number

Percent• Pseudophakic Fuchs Dystrophy 84 84%• Pseudophakic Bullous Keratopathy 12 12%• Phakic Fuchs Dystrophy 4 4%• Total 100 100%

Dry Eye Prevalence: Procedure• Procedure Number Percent• PKP 54/120 45%• DSEK 89/100 89%• Overall 143/220 65%

Dry Eye Prevalence: Indication• Indication Number

Percent• Keratoconus 16/64 25%• Corneal Scar 22/25 88%• Pseudophakic Bullous Keratopathy 27/33 82%• Pseudophakic Fuchs Dystrophy 76/84 87%• Phakic Fuchs Dystrophy 3/4 75%

Dry Eye Prevalence: Age• Indication Number

Percent• Keratoconus (young) 16/64 25%• Scar, Fuchs & PBK (older) 128/146 88%

• Pseudophakic Fuchs (young) 76/84 87%• Phakic Fuchs Dystrophy (older) 3/4 75%

Osmolarity Correlation with Clinical Dry Eye

• Penetrating Keratoplasty 52/5496%

• Endothelial Keratoplasty 83/8993%

• Abnormal Osmolarity Definition:• >307 mOsm/L in at least one eye• >8mOsm/L difference between eyes

Conclusions:• Dry eye is highly prevalent in patients anticipating corneal

transplantation surgery.• Dry eye is more prevalent in older transplant patients.• Dry eye may lead to significant peri-operative complications.• Corneal transplantation, particularly PKP, can significantly

exacerbate dry eye.• Keratoplasty patients should be screened for dry eye prior to

surgery.• Appropriate therapeutic measures should be undertaken to

control dry eye prior to keratoplasty surgery whenever possible.

• Osmolarity correlates closely with clinical dry eye in this keratoplasty population.

Acknowledgments:• Virginia Eye Foundation• Virginia Eye Consultants• Lions Medical Eye Bank of Eastern Virginia:

• A Vision Share Eye Bank

Professional Disclosures:• Alcon: Research Grants, Speaker, Advisor• Aldeyra Pharmaceuticals: Advisory Board,

Clinical Research• Allergan: Research Grants, Speaker, Advisory

Board, Media Spokesman• Bausch & Lomb, Ista, Valeant: Research

Grants, Speaker, Advisory Boards• Abbvie, Shire: Research, Advisor, Spokesman• BioTissue: Advisory Board, Clinical Research• Doctors Allergy Formula: Advisor, Investor• EyeGate Research: Advisory Board, Research,

Shareholder, Speaker• EyeRx Research: Clinical Research, Stock

Ownership• Imprimis Pharma: Advisory Board• Isis Pharmaceuticals: Research, Advisory Board• Inspire/Merck Pharmaceuticals: Research,

Speaker, Advisory Board• Insite: Research Grants• Kala Pharmaceuticals: Research, Advisory

Board• Lacrisciences: Shareholder, Advisor• LayerBio: Advisor, Investor• Lumenis: Speaker

• Lux Biosciences: Advisory, Research Grants• Novartis/Ciba Vision: Speaker, Advisory Board• NiCox: Advisory Board• Omeros: Advisory Board• OcuCure: Advisory Board, Shareholder• OcuHub: Advisor, Investor• Pfizer: Research, Speaker• RPS: Advisory, Research, Investor• Rtech: Clinical Investigator, Advisory Board• Santen: Research, Speaker, Advisory Board• Shire, SarCode Biosciences: Advisory Board,

Shareholder, Research Grant• Synedgen: Advisory Board• Science Based Health: Research, Advisory, Media

Spokesman• Senju: Research Grants• Srathspey Crowne: Investor• Talia Technology: Speaker, Advisory Board• Tear Lab: Advisory Board, Speaker, Shareholder• Tear Science: Advisory Board, Speaker• Topcon: Clinical Research Grant• Vistakon: Advisory Board, Clinical Research• Xoma, Servier: Clinical Investigator• 1-800-DOCTORS: Advisory Board, Shareholder