when Stallard 1 reported exudates, hemorrhages, pigment epithelial changes, optic disc edema, and optic atrophy in patients who had been treated with radon seeds for retinal capillary hemangioma and retinoblastoma.
clinically, patients with ocular irradiation do not suffer from night blindness or other symptoms of photoreceptor degeneration.
the time of onset of radiation retinopathy after radioactive plaque therapy ranged from 4 to 32 months (mean, 14.6 months), and after external beam radiation the onset ranged from 7 to 36 months (mean, 18.7 months).
Medical retina teaching Hany EL-Defrawy MVR fellow Bristol eye hospital
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.
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
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.
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
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.
Clinical features Flick, in 1948, described acute ocular lesions as cottonwool spots, intraretinal and preretinal hemorrhages, Roths 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.
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.
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
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.
Differential diagnosis Diabetic Retinopathy. Multiple-branch retinal artery obstructions Multiple episodes of venous occlusive disease Retinal telangiectasia from other causes
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
l.Pho TREATMENTtocoagulati Visual loss related to macular nonperfusion probably cannot be reversed.on However, several groups have applied treatment guidelines of the Earlyt Treatment Diabetic Retinopathy Study (ETDRS) to eyes with macular edemare and posterior-segment neovascularization, with favorable results. In oneat study, 12 eyes with clinically significant macular edema secondary to radiationmen were treated with focal and grid photocoagulation; eight of 12 (67%) eyest showed improvement in macular edema after laser therapy, with six (50%)fo eyes having complete resolution of clinically significant edema after a meanr follow-up of 39 months. Vision improved from a median preoperative levelcl of 20/100 to 20/75 at the time of final examination. Macular ischemia,in cataract, and radiation optic neuropathy were noted in all eyes andic contributed to vision loss in some cases.allysi 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; ificantrad
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.
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.
Prognosis Three situations appear to exacerbate radiation retinopathy1. Patients who have a pre-existing microangiopathy appear to be more prone to developing severe changes2. 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.