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LASER PHOTOCOAGULATION AS MANAGEMENT OF RETINOBLASTOMA
AbstractIntroductionThe management of retinoblastoma can be complex, and it is impossible to establish firm rules regarding treatment. There are several options available for the treatment of retinoblastoma, and the method selected should depend on the size and extent of the tumor(s), whether there is unilateral or bilateral involvement, and the patient’s systemic status. Lasers have played a central role in the treatment of retinoblastomas since the very start of the laser era.ObjectivesTo review two cases of retinoblastoma treated by photocoagulation therapyCaseAn one-month old baby boy came with his parent with chief complain white freckle in his right eye. From evaluation under anesthesi (EUA), two intraocular masses on inferolateral quadrant were found, size of two masses were 0,5 DD (disc diameter) and 1 DD. He was diagnosed as intraocular masses ec suspect retinoblastoma grade A OD. Photocoagulation with diode laser (810 nm) was performed. One month after laser therapy, the size of intraocular masses was same as before. A three-month old baby girl came with chief complain white freckle on herleft eye since two weeks ago. Patient was diagnosed as retinoblastoma grade B OD et grade D OS. He had undergone chemotherapy, laser photocoagulation for her right eye, and cryo therapy for her left eye. Five years later intraocular mass in herleft eye progressed, she was diagnosed as retinoblastoma grade B OD et grade D-E OS and suggested to enucleation OS. Enucleation of left eye was performed. ConclusionPhotocoagulation can be used as local primary therapy and consolidation treatment following primary systemic chemotherapy to eliminate the tumor cells that were resistant to or were not inactivated by primary therapy. Photocoagulation alone, as local primary therapy, appears to be an appropriate method of management in cases where the tumor is small in diameter.
I. Introduction
Retinoblastoma is the most common malignant ocular tumor of childhood,
with incidence of 1:14.000-1:20.000 live births. This neuroblastic tumor is
typically diagnosed during the first year of life in familial and bilateral cases and
between ages 1 and 3 in sporadic unilateral cases. The most common initial sign is
leukokoria (white pupil) described as a glow, glint, or cat’s eye appearance. Other
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presentations include vitreous hemorrhage, hyphema, ocular or periocular
inflammation, glaucoma, proptosis, and pseudohypopion.1,2
The first goal of retinoblastoma must be preservation of life, then
preservation of eye, and finally preservation of vision. The management of
intraocular retinoblastoma currently incorporates a combination of different
treatment modalitas, including enucleation, chemotherapy, photocoagulation,
cryotherapy, external beam radiation therapy, and plaque brachiotherapy.
Photocoagulation therapy using xenon arc and argon laser (532 nm) or diode laser
(810 nm) have been used to treat retinoblastoma smaller than 3 mm in apical
height with asal dimensional less than 10 mm. Over the years, the result were
comparable between the various types of laser, and a tumor control rate of
approximately 80% was achieved. The currently popular diode laser, used with an
adjustable, indirect opthalmoscope, is far easier to use than the xenon arc
photocoagulator, and moreover has a more favorable absorption range within the
eye than the argon laser.1,3
This study reports a case series of retinoblastoma which treated with
photocoagulation laser therapy in vitreoretinal department of Cicendo Eye
Hospital.
I. Case Report
II.1 Case I
An one-month old baby boy, baby K, came with his parental to vitreoretina
department of Cicendo Eye Hospital. His parents complain about white freckle in
their son’s right eye. Patient was born in the hospital normally through vaginal
birth on 37 weeks of gestation, his birth weight was 3100 grams. There was no
history of illness during pregnancy. He was born from a G1P1A0 mother. On one
month old, his weight was 5330 grams.
From ophthalmological examination, visual acuity was blink reflex for both
eyes. Anterior segment examination was within normal limit. Funduscopy
examination of right eye revealed clear media, round papil, clear border, c/d ratio
0,3-0,4, a/v ratio 2:3, flat retina, fovea reflex (+), two intraocular masses on
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inferolateral quadrant, their size were 0,5 DD (disc diameter) and 1 DD.
Funduscopy examination of left eye was within normal limit, optic disc drusen
(+).
This baby boy was diagnosed multiple intraocular masses e.c susp
retinoblastoma grade A OD + optic disc drusen OS. This patient was consulted to
pediatric ophthalmology unit to undergo retcam examination and his condition
was informed to his parent. The following is his first retcam photograph.
Figure 2.1 Retcam photograph of both eyes before laser treatmentSource : Cicendo Eye Hospital
He was suggested to undergo laser treatment for masses on right eye. One
month later, he undergone laser therapy surrounding the masses in general
anesthesia with infrared (810 nm), duration was 0,20 second, power was 300 mW,
amount of laser spot was 313.
One month after laser treatment, he and his parents came to follow up. On
second month old, his body weight was 4000 gram. Anterior segment examination
was within normal limits for both eyes. Funduscopy examination of right eye
revealed two intraocular lesions on inferolateral quadrant, their size were still 0,5
DD (disc diameter) and 1 DD, scar laser surrounding lesions, pre-lesions
hemorrhage (+), the others were same as before. Funduscopy examination of left
eye was within normal limit, optic disc drusen (+), NV (-), slight turtoisity. Patient
undergone retcam examination and his parent was adviced to come next month.
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Figure 2.2 Retcam photograph of both eyes one month after laser treatmentSource : Cicendo Eye Hospital
II.2 Case II
A-three month old baby girl, baby A, came on January 2010 with her
parents to Cicendo Eye Hospital with chief complain white freckle on her left eye
since two weeks ago. She was born through caesarian delivery with birth weight
2715 grams from a G2P2A0 mother on 37 weeks of gestation. Her sister is 2,5
year folder than hers. No history of ilness during pregnancy. No history of ocular
tumor in her family. Ophthalmological examination revealed blink reflexes for
both eyes. Anterior segment examination showed cat’s eye (+) on the left eye,
others were within normal limit. Patient underwent first ultrasonography (USG)
examination and was diagnosed as intraocular mass e.c retinoblastoma ODS
(OS>OD). She got chemotherapy from hemato-oncologist pediatrician. CT scan
examination revealed exophytic mass e.c suspect retinoblastoma OS, 18x12x17
mm. No expansion to retrobulbar space or optic nerve or intracranial. Suspect
small retinoblastoma OD juxta optic disc, confined to oculi, measuring 3 mm.
Three months later on April 2010 from USG, there was regression of
intraocular mass of left eye, vitreous cavity was clearer while intraocular mass on
right eye was as small as before. Second CT scan revealed that the mass in left eye
had shrunk, there was no soft tissue mass, only calsified nodule 10x4x13 mm, no
expansion to optic nerve or intracranial. There was no mass in right eye ball.
Four months later on August 2010 USG of right eye showed an echogenic
mass, 4,46 mm x 0,81 mm, moderate to high reflectivity, no mobility and a mass
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13,5 mm x 2,91 mm, calcification (+), shadowing (+) on left eye. Baby A was
diagnosed as retinoblastoma grade B ODS. Three months later, she underwent
evaluation under anestesi (EUA) and photocoagulation therapy. From indirect
funduscopy on right eye there were retina flat, tumor with diameter was a half of
disc diameter, calsification (+), while there was mass about half of posterior eye
ball about 2 DD, solid, vitreous seeding (+). The patient was diagnosed as
retinoblastoma grade B OD et grade D OS. The tumor was responsive to
chemotherapy. Patient underwent photocoagulation OD using LIO (laser indirect
ophthalmoscopy) diode 810 nm during EUA, then continued her chemotherapy.
Figure 2.3 showed USG examination of left eye
Source : Cicendo Eye Hospital
Seven months later (on June 2011), from indirect funduscopy on right eye there
were retina flat, tumor with diameter was a half of disc diameter, calsification (+), while
there was mass about half of posterior eye ball about 2 DD, solid, vitreous seeding (-).
Patient was diagnosed as retinoblastoma grade B ODS (resolving). CT scan revealed no
mass on right eye and a solid mass with calcified nodule size 4 x 10 x 12 mm, no
extension to optic nerve or intracranial on left eye.
Seven months later (on January 2012) she underwent EUA. Indirect funduscopy
examination revealed a mass with size 1,5 DD on superior portion, vitreous seeding (-),
laser scar (+) and a mass with size 4 DD on inferior, laser scar (+), with cherry with
appearane in the center of mass on right eye and chery white mass 8 DD, calcified,
vitreous seeding (+) on inferiortemporal quadrant and cyctic mass, more than 4 DD. She
was diagnosed as retinoblastoma gr B-C OD et gr D-E OS and suggested to enucleation
OS + photocoagulation OD. Two months later right eye was treated by cryotherapy.
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On July 2012 EUA revealed on right eye tumor mass, flat retina, laser scar, no
vitreous seeding and on left eye increased size of tumor mass, neovascularization,
increased vitreous seeding. She was suggested to continue the chemotherapy and focal
radiotherapy after consulted to pediatrician, and observation of left eye.
On November 2012 EUA revealed on right eye white tumor mass on superior and
inferior, 7-8 DD, clear border, flat with vascularization on the mass, suggestive
retinoblastoma grade B. On left eye there was retinal detached, vitreous seeding, tumor
mass on lateral portion with clear border, vascularization, elevated but not clear border,
diameter 20 DD, suggestive retinoblastoma grade D-E. Patient was suggested to
enucleation of left eye. Visual acuity was 0,5 with cardiff 50 cm. This patient had
undergone 50 times chemotherapy in Hasan Sadikin Hospital. Her liquor cerebrospinal
fluid (LCS) examination result revealed there was no blast cell. On March 2015, her
visual acuity of right eye 0,8 with cardiff 1 meter and no light perception (NLP) for left
eye, then enucleation was perfomed. Pathology anatomy examination result showed that
retinoblastoma of left eye has invaded choroid and optic nerve.
Figure 2.2 Retcam photograph of left eye on July 2012 and November 2012
Source : Cicendo Eye Hospital
II. Discussion
Any white or yellow lesion in the posterior segment of the eye in a child
under 5 years of age should raise the possibility of retinoblastoma. This disease is
highly curable in its early stages but can be fatal if the diagnosis is missed or
delayed. In a large majority of children with this disease, including this case, a
parent or family member first notes the presence of a white pupillary reflection or
reflex (leukocoria). A posterior pole tumor as small as 3 to 5 mm in diameter has
the capacity to create leukocoria. The term that parents use for the leukocoria
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observation is rarely the textbook-cited “cat’s eye.” Usually it is a “g” word, such
as “gleam, glow, glare, or glint”.4
The differential diagnosis of leukocoria are retinoblastoma, persistent
hyperplastic primary vitreous (PHPV), cataract, retinopathy of prematurity,
toxocariasis, coloboma of choroid, uveitis, coat’s disease, vitreous hemorrhage,
retinal dysplasia, tumors other than retinoblastoma, retinal detachment, corneal
opacity, and myelinated nerve fibers. Other presentations beside leukocoria
include vitreous hemorrhage, hyphema, ocular or periocular inflammation,
glaucoma, proptosis, and pseudohypopion.4
In case 1, this baby boy was diagnosed as suspect retinoblastoma grade A
OD + optic disc drusen OS because there was complain of leukocoria from his
parent and there were multiple white masses on retina from funduscopy
examination of right eye. According to International Retinoblastoma
Classification, this patient was suspected retinoblastoma grade A because group A
tumor are still small less than 3 mm in any diameter (base or height), no vitreous
seeding and located greater than 2 DD (3 mm) from the fovea and 1 DD (1,5 mm)
from the optic disc.
In case 2, this baby girl was diagnosed as suspect retinoblastoma grade B
OD et grade D OS because on her right eye the tumor was greater than 3 mm in
any diameter but there was not vitreous seeding or subretinal fluid and on the left
eye the tumor was large intraocular mass (endophytic disease) and diffuse vitreous
seeding.
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Table 3.1 International Retinoblastoma Classification: Grouping SystemSource : Rosa1
There are several options available for the treatment of retinoblastoma, and
the method selected should depend on the size and extent of the tumor(s), whether
there is unilateral or bilateral involvement, and the patient’s systemic status. In the
early 1990s several investigators from North America and Great Britain began
using systemic agents to treat intraocular retinoblastoma (CEV regimen,
comprising carboplatin, etoposide, and vincristine) that had been found to be
successful in the treatment of central nervous system neoplasms. Other indications
for chemotherapy in a patient with retinoblastoma include prophylaxis against
metastasis following enucleation in the presence of histopathologic high-risk
features, extraocular retinoblastoma with local and/or regional spread, metastatic
retinoblastoma with or without CNS involvement, and trilateral retinoblastoma.
Retinoblastoma in patients with bilateral disease or only moderately advanced
unilateral disease diagnosed today are treated with a protocol of systemic
chemotherapy given intravenously every 3 to 4 weeks followed by consolidation
(the use of a different dose of the same drug, a different drug, or different
treatment modality) with the focal surgical techniques of direct tumor
photocoagulation or cryotherapy or both.5
The two most common surgical procedures used as part of the treatment of
intraocular retinoblastoma are local therapy, either primary or for consolidation
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following systemic chemotherapy, and enucleation. Photocoagulation,
thermotherapy, chemothermotherapy, cryotherapy, brachytherapy, and external
beam radiotherapy could be considered local therapy.5,6
Tabel 3.2 Local treatment of retinoblastomaSource : Wright4
Photocoagulation is described by Meyer-Swickerath in 1949,
photocoagulation involves heating the tumor to temperatures above 65°C.
Photocoagulation can be used as primary treatment, consolidation treatment, and
for tumor recurrence. Group A eyes with small intraretinal lesions away from
critical structures are candidates for local primary therapy, such as direct laser
photocoagulation or cryotherapy. Loss of central vision from direct tumor
destruction or laser consolidation during treatment is minimized in group A by
restricting the tumor to locations greater then 2 DD (3 mm) from the fovea and 1
DD (1,5 mm) from the optic disc. The prognosis of group A is excellent.4,5,6
Photocoagulation treatment can use argon green laser (532 nm), diode
laser (810 nm), and transpupillary thermotherapy (TTT) using infrared diode laser
(810 nm) that couples large spot size (2–3 mm) and long burn duration (1 minute)
with low power settings. In these cases, patients were treated with diode laser
(810 nm).3,4,7 Patient of case 1 had photocoagulation as local primary therapy
according to grade A and still require follow up. Patient of case 2 had
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photocoagulation as consolidation therapy, following systemic chemotherapy for
retinoblastoma grade B OD et grade D OS.
The 810 nm diode laser is most effective when there is intact RPE beneath
the tumor. The indirect ophthalmoscope delivery system offers a spot size of 0.5
mm. This provides safety from the reduced likelihood of concentrated power
intensity in a small spot creating explosive disruption of the tumor and short
treatment time.3,4,5
Initial setting were 400–500 mW and 0,5–1,0 seconds. The power and
duration will vary for each patient because of the degree of pigmentation
underlying the lesion. Once the appropriate power level is set, the edge of the
tumor is treated with overlapping burns to establish its perimeter. Subsequently
the entire lesion should be treated with burns having the same overlap. In the
central, thicker portions of the tumor, the whitening reaction following treatment
may not be present. The treatment is repeated every 3–4 weeks immediately
before the next cycle of chemotherapy. A 2–4-week interval can be adopted if the
systemic chemotherapy has been completed.3,4,5
The most important effect is the direct heat mediated tumor cell kill. The
diode laser is most effective when intact RPE is present beneath the tumor to be
treated. If the RPE has been destroyed, most of the 810 nm wavelength energy
passes into the orbit without being absorbed by the retinoblastoma.3,4,5
When treating retinoblastomas with an indirect ophthalmoscope, children
should be anesthetized and the surgeon should first treat the area surrounding the
tumor and then the tumor itself, until the effect of coagulation is visible. Over-
treatment, for example, a power that is too high or a long exposure time, may
cause the spread of tumor cells within the vitreous cavity. This is a severe, eye
threatening complication. Others complications are retinal fibrosis and traction,
and retinal vascular occlusion. Tumors treated by laser coagulation should be
monitored closely since recurrent disease may develop even years after the initial
therapy.4,5
Study about retinoblastoma treated with photocoagulation only revealed
that photocoagulation appears to be an appropriate method of management in
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cases where the tumor is no greater than 3.0 mm in diameter and 2.0 mm in
thickness and is confined to the sensory retina, without seeding into the adjacent
vitreous. Photocoagulation alone is generally unsuccessful for tumors greater than
4.5 mm in diameter and greater than 2.5 mm in thickness and supplemental
treatment with other modalities was often necessary in such cases. Complete
regression occurred in 21 tumors (70%) and local recurrence in nine (30%).8
A case report about 18-month-old girl, a small (6.6x 4.3x 3.2-mm) discrete
retinoblastoma anterior to the superotemporal arcade in the right eye was treated
with transscleral photocoagulation using a diode laser (810 nm) and a fiberoptic
probe. The tumor regressed after photocoagulation, leaving a pigmented
chorioretinal scar. There was no regrowth of the tumor 12 months after
photocoagulation. The advantages of transscleral over transpupillary delivery
include the ability to treat tumor in the presence of media opacities, the larger
available spot size, and the avoidance of transmitting laser through the pupil,
which eliminates the risks of cataract and synechiae.9
III. Conclusion
Photocoagulation can be used as local primary therapy and consolidation
treatment following primary systemic chemotherapy to eliminate the tumor cells
that were resistant to or were not inactivated by primary therapy.
Photocoagulation alone, as local primary therapy, appears to be an appropriate
method of management in cases where the tumor is small in diameter. Complete
regression occurred in 70% cases and local recurrence 30% cases.
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