1. Medical retina teaching
Hany EL-Defrawy
MVR fellow
Bristol eye hospital

2.  A 68 year old lady presented to BEH in 2011
Complaining watering of both eyes
 Syringing revealed bilateral NLD obstruction
 POH: SCC diagnosed in 2005 involving the nasal cavity
for which she received cephalic radiation over 5
months
 Anterior segment examination was unremarkable
 Fundus examination showed retinal hemorrhages ,and
disc neovascularization.
 Visual field defect.

5. Radiation retinopathy
 Radiation retinopathy is characterized by delayed onset
of slowly progressive occlusive vasculopathy that may
lead to capillary non-perfusion, large-vessel occlusion,
retinal vascular incompetence, neovascularization, and
other sequelae. These changes may cause loss of visual
function.
 First report of posterior-segment complications
following radiation therapy appeared in 1933

6.  Studies performed on monkeys and rats treated with 15-30 Gy
showed
 Focal loss of capillary endothelial cells and pericytes with cotton-
wool spots seen clinically.
 large areas of retinal capillary non-perfusion.
 Histopathologic studies showed that the first changes involved
deep, small retinal vessels. Larger vessels were involved later
 Occlusion of the choriocapillaris
 Intraretinal neovascularization
 Irvine AR, Wood IS. Radiation retinopathy as an experimental model for ischemic proliferative retinopathy
and rubeosis iridis. Am J Ophthalmol 1987; 103:790-797
 Archer DB, Amoaku WMK, Gardner TA. Radiation retinopathy: clinical, histopathological, ultrastructural,
and experimental correlations. Eye 1991; 5:239-251.

7. Histopathology
 Endothelial cell damage occurs in the arterial circulation as a result of free
radical generation in this high-oxygen environment. After an initial wave of
cell death, the remaining viable endothelial cells replicate and migrate to
maintain vascular architecture. Later cycles of endothelial cell death occur
during mitosis as a result of radiation-induced damage to chromosomal DNA.
 In contradistinction to diabetic retinopathy, in which pericyte loss
predominates, a predilection for endothelial cell loss was identified in cases
with radiation injury
 The vascular endothelium becomes discontinuous, resulting in intraluminal
coagulation and capillary closure characteristic of radiation retinopathy.
 Archer DB, Amoaku WMK, Gardner TA. Radiation retinopathy: clinical, histopathological, ultrastructural, and experimental correlations. Eye
1991; 5:239-251.
 Archer DB. Doyne lecture: responses of retinal and choroidal vessels to ionizing radiation. Eye 1993; 7:1-13

8. Sequale
 Studies in humans have shown loss of ganglion cells secondary to neovascular
glaucoma, cystic changes in the outer plexiform and inner nuclear layers, and
thickening of the vessel walls from deposition of fibrillary or hyaline material.
There may be myointimal proliferation in larger vessels.
 There is preferential damage to inner retinal layers
 Photoreceptors appear to be relatively resistant to radiation damage
 Subretinal and choroidal neovascularization (CNV) has been reported as a
rare complication of ocular irradiation
 Brown GC, Shields JA, Sanborn G et al. Radiation retinopathy. Ophthalmology 1982; 89:1494-1501.
 Egbert PR, Fajardo LF, Donaldson SS et al. Posterior ocular abnormalities after irradiation for retinoblastoma: a histopathological study. Br J
Ophthalmol 1980; 64:660-665.
 Ross HS, Rosenberg S, Friedman AH. Delayed radiation necrosis of the optic nerve. Am J Ophthalmol 1973; 76:683-686.

9. Clinical features
 Flick, in 1948, described acute ocular lesions as cottonwool
spots, intraretinal and preretinal hemorrhages, Roth's spots in
survivors of the atomic blasts at Hiroshima and Nagasaki.
 Delayed radiation damage to retinal blood vessels causes vascular
incompetence and occlusion. This include capillary dilation,
telangiectasias, microaneurysm formation, and capillary closure,
retinal ischemia ,retinal , disc neovascularization, vitreous
hemorrhage, and retinal detachment .
 Exudative phenomena resulting from retinal vascular
incompetence may occur with preferential involvement of the
macula.
 Flick JJ. Ocular lesions following the atomic bombing of Hiroshima and Nagasaki. Am J Ophthalmol 1948; 31:137-154.

10.  Spaide and collegues reported an unusual choroidal vascular
anomaly in patients receiving external beam radiation to treat
subfoveal CNV secondary to age-related macular degeneration.
In this retrospective analysis, 193 patients were evaluated: these
patients underwent treatment with either 10 to 12 Gy or 20 Gy
external beam photons. Nineteen patients (9.8%) developed
round to oval vascular blebs along the periphery of the CNV that
showed marked leakage of fluorecein dye on angiography. These
lesions, termed radiation-induced choroidal neovasculopathy,
were best imaged using indocyanine green angiography. Patients
who developed this finding tended to have a poor visual
prognosis.
 Spaide RF, Leys A, Herrmann-Delemazure B et al. Radiation-associated choroidal neovasculopathy.
Ophthalmology 1999; 106:2254-2260.

11. External beam radiation vs
Brachytherapy
 In the 1982 report by Brown and colleagues involving 36 eyes with radiation retinopathy
 20 patients had received radioactive cobalt plaques (brachytherapy) for the treatment of
intraocular tumors. Eighty-five percent of these patients developed hard exudates, 75% showed
microaneurysm formation, 65% had intraretinal hemorrhages, 35% had retinal vascular
telangiectasia, 30% had cottonwool spots, and 20% showed vascular sheathing.
 The 16 patients who received external beam irradiation (teletherapy) showed hard exudates in
38% of cases, microaneurysms in 81%, and intraretinal hemorrhage in 88%. Retinal vascular
telangiectasia and cottonwool spots were seen in 38% of these patients, and vascular sheathing
was apparent in 25% of cases.
 Brown and co-workers postulate that the increased frequency of hard exudate formation in
patients treated with brachytherapy rather than teletherapy may have been connected with
vascular leakage related to the intraocular neoplasm, and not simply the radiation therapy alone
 One of the 20 plaque-treated patients developed posterior-segment neovascularization, as
compared with seven of 16 patients treated with external beam radiation. Four of the 16 patients
subsequently developed neovascular glaucoma.
 Neovascularization is more frequent in patients who are treated with external beam radiation , as
the entire retinal area receives the dose as opposed to a localized area following radioactive plaque
therapy

13. INCIDENCE AND DOSIMETRY
 It is generally accepted that the incidence of radiation retinopathy depends on
both the total radiation dose and fraction size.
 Using both retrospective and prospective data, authors analyzed 68 eyes of 64
patients receiving teletherapy for extracranial tumors.
 Doses in the 45 to 55 Gy range delivered to half or more of the retina
produced a 53% rate of retinopathy, with the risk increased by diabetes,
chemotherapy, and high dose per fraction.
 In a study of 64 patients receiving iodine-125 brachytherapy for uveal
melanoma, a 23.4% incidence of radiation retinopathy and a 18.8% incidence
of rubeosis iridis after a mean follow-up of 64.9 months. Radiation doses for
the iodine-125 plaque were calculated at between 80 and 100 Gy
 Parsons JT, Bova FJ, Fitzgerald CR et al. Radiation retinopathy after external beam irradiation: analysis of time-dose factors. Int J
Radiat Oncol Biol Phys 1994; 30:765-773.
 Packer S, Stoller S, Lesser ML et al. Long-term results of iodine 125 irradiation of uveal melanoma. Ophthalmology 1992; 99:767-
774.

14. Differential diagnosis
 Diabetic Retinopathy.
 Multiple-branch retinal artery obstructions
 Multiple episodes of venous occlusive disease
 Retinal telangiectasia from other causes

15. Diagnosis
 Questioning the patient and determining if there has been
radiation therapy in the past.
 A review of the treatment records will permit the
ophthalmologist to determine whether the eyes were included in
the field of radiation.
 Diagnosis of radiation retinopathy should be considered
following cephalic radiation for any reason.
 Radiation retinopathy has been reported after orbital treatment
for thyroid disease and for orbital pseudotumor, as well as after
intracranial radiation therapy for both primary and metastatic
central nervous system tumors, paranasal sinus radiation
therapy and can occur after radiation therapy for skin tumors of
the face and lids

16. l
.
P
h
o
TREATMENT
t
o
c
o
a
g
u
l
a
t
i
 Visual loss related to macular nonperfusion probably cannot be reversed.
o
n
However, several groups have applied treatment guidelines of the Early
t Treatment Diabetic Retinopathy Study (ETDRS) to eyes with macular edema
r
e and posterior-segment neovascularization, with favorable results. In one
a
t study, 12 eyes with clinically significant macular edema secondary to radiation
m
e
n
were treated with focal and grid photocoagulation; eight of 12 (67%) eyes
t showed improvement in macular edema after laser therapy, with six (50%)
f
o
eyes having complete resolution of clinically significant edema after a mean
r follow-up of 39 months. Vision improved from a median preoperative level
c
l
of 20/100 to 20/75 at the time of final examination. Macular ischemia,
i
n cataract, and radiation optic neuropathy were noted in all eyes and
i
c contributed to vision loss in some cases.
a
l
l
y
s
i  Kinyoun JL, Chittum ME, Wells CG. Photocoagulation treatment of radiation retinopathy. Am J Ophthalmol 1988; 105:470-478.
g 
n
Kinyoun JL, Zamber RW, Lawrence BS et al. Photocoagulation treatment for clinically significant radiation macular oedema. Br J Ophthalmol 1995;
i
f
i
c
a
n
t
r
a
d

17. TREATMENT
 Hykin and co-workers examined the efficacy of ETDRS-type treatment for
eyes with clinically significant radiation macular edema (CSRME) secondary
to scleral plaque radiotherapy for choroidal melanoma. In this retrospective
study, 19 cases treated once with focal laser were compared to a matched
group of 23 eyes with CSRME receiving no treatment. Treated eyes showed
significant benefit with respect to vision improvement at 6 months, with 8/19
(42%) gaining ≥ 1 Snellen line versus no cases in the untreated group. A trend
was noted in the treated group towards resolution of macular edema at 6
months and towards less vision loss at 12 months following focal laser.
However, early improvement in vision and edema in the treated group was
not sustained
 The authors concluded that a single treatment with focal laser will not result
in sustained benefit and that additional treatments may be indicated for
persistent or recurrent CSRME.
 Hykin PG, Shields CL, Shields JA et al. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology 1998; 105:1425-
1429.

18.  In an earlier report, Kinyoun et al.described treatment of six eyes with high-
risk neovascularization by panretinal photocoagulation. Three eyes had
regression of new vessels, with no recurrent vitreous hemorrhages within 19
to 66 months' follow-up. Pars plana vitrectomy was performed in three eyes
with nonclearing hemorrhages, with improvement in vision. Kinyoun et al.
later reported a success rate of 91% in 11 eyes treated with panretinal
photocoagulation for proliferative radiation retinopathy. 22 However, long-
term visual outcome in this group was poor, with few eyes retaining vision
better than 20/200.
 Kwok et al analyzed the occurrence of neovascular glaucoma in a group of 50
eyes undergoing cataract surgery after external beam radiation. Panretinal
photocoagulation significantly reduced the incidence of neovascular glaucoma
after cataract surgery, with 5 of 15 without laser and 0 of 35 eyes with laser
developing neovascular glaucoma.

19. Prognosis
 Three situations appear to exacerbate radiation
retinopathy
1. Patients who have a pre-existing microangiopathy
appear to be more prone to developing severe changes
2. Diabetic patients are more likely to show changes
following lower doses of radiation than are non-
diabetic patients.
3. Patients who receive certain chemotherapeutic agents.

20. Thank you