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Fluorescein Angiographic Features, Natural Course and Treatment of Radiation Retinopathy

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Fluorescein Angiographic Features, Natural Course and Treatment of Radiation Retinopathy Eye (1990) 4, 657-667 Fluorescein Angiographic Features, Natural Course and Treatment of Radiation Retinopathy W. M. K. AMOAKU and D. B. ARCHER Belfast Summary Fifteen patients who developed retinopathy following radiotherapy for cephalic tumours were studied by fluorescein angiography. Nine patients with unilateral or bilateral retinopathy had serial angiograms at six monthly or yearly intervals. Angiography revealed a wide range of retin;tl microvascular changes which were graded 1-4 according to the extent and degree of capillary malformation, incom­ petence and closure. All patients showed slow progression of retinopathy with remo­ delling of the affected microvasculature and increased capillary fallout and leakage to dye. The earliest retinopathic changes were capillary dilatation and closure and micro­ aneurysm formation. Telangiectatic-like vessels were a feature of the established ret­ inopathy and probably represented collateral channels which bordered sites of capillary occlusion. Two patients with progressive macular oedema and declining vision responded favourably to focal laser photocoagulation which returned a measure of competence to some residual dilated capillaries. The first fluorescein angiographic features of leading to the development of radiation radiation retinopathy were described by retinopathy. Chee' and Gass2 who reported a microvas­ Thompson et al.6 studied seven patients culopathy characterised by capillary incom­ with radiation retinopathy and highlighted petence and closure. In 1970, Hayreh3 studied the value of fluorescein angiography in accu­ three patients with choroidal melanoma rately identifying the microvascular alter­ treated by Cobalt 60 applicators and docu­ ations. Ehlers and Kaae7 also used fluorescein mented a wide range of angiographic changes angiography to determine the extent of retinal in the retinal vasculature and outer retina. and choroidal vaso-occlusive changes in Bagan and Hollenhorst4 reported six cases of infants receiving radiotherapy for retinoblas­ radiation retinopathy but angiographic toma. Lommatzsch et al. 8,9 and Tarkkanen changes were only described in one patient. and LaatikainenlO documented the regression Brown et al.5 reviewed the angiographic of choroidal melanomas treated with Ru 106/ changes in the retinae of patients receiving Rh 106 plaques using angiographic tech­ external beam or plaque therapy for intra­ niques. They reported the disappearance of ocular tumours and identified vascular occlu­ most choroidal and retinal vessels within the sion as the key pathophysiological event irradiated area and noted that chorioretinal This research was supported by a grant from the British Council for Prevention of Blindness, Correspondence to: Professor D, B. Archer, Eye and Ear Clinic, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, Northern Ireland. 658 W. M. K. AMOAKU AND D. B. ARCHER vascular occlusion and retinal pigment epi­ 58.5 months, (mean follow-up time 25.8 thelial atrophy continued for one year or months) (Table II). more following irradiation. Two patients had laser photocoagulation Several authors using fluorescein angio­ for progressive retinopathy and persistant graphy have commented on the inexorable macular oedema. As the affected microv.as­ nature of radiation retinopathy,5.6,11,12 culature involved the central macula in both although some have noted its progression may instances, the Argon green laser was chosen. be slow.4 Natural regression of the disease Photocoagulation was applied to microvas­ process has also been reported in a few cular lesions, - particularly microaneurysms instances. 13,14,15 and telangiectatic-like capillaries and nearby Most studies of radiation retinopathy to this retina. Areas of ischaemic and poorly per­ time are either case reports or single obser­ fused retina were also treated. No burns were vations in small cohorts of patients receiving placed within 750 �m of the centre of the ocular brachytherapy or teletherapy. In most foveola. The first treated eye received a total instances the disease process is advanced or of 448 burns (100 �mxO.1 secxO.3 W) in two end-stage and few descriptions of the early sessions. The second treated eye received 250 vascular changes have been available. burns (100 �mxO.1 secxO.18 W). Supple­ Sequential investigations of retinopathy have mentary treatment of 181 burns (100 �m x been reported from time to time;4,6,15 how­ 0.1 sec x 0.2 W) was given to the second ever, the natural course of the vasculopathy, patient after three months. particularly the early stages, has not been studied in detail. This paper describes the tlu­ Results orescein angiographic changes in the retinae In most patients with established radiation of patients receiving cephalic radiation retinopathy angiography demonstrated emphasising the initial vascular alterations striking and characteristic changes in the and documenting the natural course of the architecture and structure of the retinal disease process. The modifying effects of laser microvasculature with varying degrees of cap­ photocoagulation on the natural progression illary incompetence and closure. Typically, of the vasculopathy are also examined. the retinopathy was concentrated in the mac­ ular and peripapillary regions; however, two Materials and Methods patients in whom the radiation field was Fifteen patients who developed retinopathy eccentric to the eye developed asymmetrical following cephalic radiation in Northern retinopathy corresponding to the respective Ireland between 1972 and 1988 were studied fields of irradiation. One of these patients, by fluoresceinangiography . The tumour path­ (Case 3), a diabetic without discernible ret­ ology, tumour sites, radiation doses and meth­ inopathy showed widespread microaneu­ odology are documented in Table I. rysms, haemorrhages and ischaemia in the Each patient had a full assessment of visual irradiated superior retina of the right eye functions, ocular biomicroscopy and fundus (Fig. 1). The inferior retinae displayed little examination. Fluorescein angiograms were or no evidence of retinopathy. The second obtained with a Zeiss fundus camera follow­ patient (Case 15) with asymmetrical retino­ ing an intravenous injection of 5 ml of 20% pathy had received radiation for a malignant sodium fluorescein. High quality angiograms melanoma of the nose and the inferior retina in one patient permitted a quantitative assess­ had been included in the radiation field. Sub­ ment of microvascular changes using a Kodak sequently this patient presented with exten­ Image Analyser. sive areas of ischaemia in the inferior retina Nine patients with retinopathy were fol­ associated with preretinal neovascularisation. lowed, and serial angiograms taken at six Three patients showed evidence of retinal month or one year intervals. In six patients pigment epithelial degenerative changes review was not possible due to advancing lens particularly atrophy and proliferation. A or corneal opacities or deteriorating health. further patient who received direct orbital The time of follow-up varied between 13 and irradiation demonstrated a large subretinal FLUORESCEIN ANGIOGRAPHIC FEATURES 659 Table I Radiation retinopathy-a fluorescein angiographic study Radiation, Case dose Systemic Angiography No. Patient Eye Tumour site fractionation Date Chemotherapy disease initial date 1 A.C. R Nasopharynx 5250 cGy/25f Sept 1981 23.9.86 2 B.C. R (L) Nose and 5000 cGy/25f Jan 1984 7.5.85 L Ethmoid 29.1.87 3 B.D. R (L) Parieto- 4000 cGy/30f Nov 1984 CCNU* Diabetes 11.10.86 L temporal mellitus 1979 lobe 4 H.D. L (L) Lacrimal 2750 cGy/20f Aug 1983 Vincristine, 9.5.88 sac Cyclophosphamide, 5-FUt 5 A.H. R (R) Orbit 3350 cGy/15f lan 1972 26.3.87 6 D.H. R (R) Orbit 4800 cGy/20f Dec 1978 Actinomycin D 17.10.88 Vincristine, Cyclo- phosphamide 7 S.l. R Nasopharynx 5000 cGy/25f March 1978 27.5.86 L 27.5.86 8 H.K. L (L) Orbit 3417 cGy/15f Nov 1981 27.4.88 9 H.M. R (R) Maxillary 4350 cGy/20f Oct 1977 3.6.86 antrum Ethmoid 10 1.M. R (R) Orbit 3500 cGy/19f Jan 1981 Diabetes 28.4.88 mellitus 1987 11 A.M. R Nasopharynx 5250 cGy/25f Feb 1978 6.1.87 L 6.1.87 12 N.O. L (L)Lacrimal 5500 cGy/25f Feb 1988 Diabetes 7.12.87 R sac 2400 cGy/25f mellitus 1987 7.12.88 13 J.O. R Nasopharynx 4424 cGy/24f Oct 1983 5FUt Diabetes 30.6.86 L mellitus 1982 30.6.86 14 M.S. L (L) Maxillary 5460 cGy/26f Nov 1979 6.1.87 antrum 15 AT. L (L) Nose 5000 cGy/25f lan 1981 Tamoxifen (for 24.6.86 breast Ca) * CCNU 1-(2-Chlorethyl)-3-Cyclohexyl-l-Nitrosurea. t 5FU 5-Fluorouracil. neovascular membrane at the macula. Details fluid accumulation within the retina (Fig. 2). of the angiographic findings and follow-up Visual functions were good in these patients period for each patient are listed in Table II. i.e. 6/6 or better. 1. Grading of angiographic changes Grade 2 Retinopathy All varieties of reported microvascular Seven eyes showed multiple foci of dilated response to radiation were identified in this and telangiectatic-like capillaries and zones of study, and 15 patients (20 eyes) were classified capillary closure up to one optic disc area in according to the degree and extent of the dimension. This group also showed numerous microvascular changes. microaneurysms and focal leakage of dye from defective capillaries in later phase angio­ Grade 1 Retinopathy grams (Fig. 3a, b). In some patients fluores­ Two eyes demonstrated small foci of dilated cein leakage was associated with clinically and irregular retinal capillaries in association observable retinal oedema, although cystoid with isolated or small clusters of microaneu­ macular changes were absent and visual rysms. These eyes also showed subtle evi­ acuity remained relatively good, i.e. 6/9 or dence of capillary closure, although there was better. One patient (two eyes) in this group no detectable microvascular incompetence or (Case 13) was diagnosed as suffering from 660 w. M. K. AMOAKU AND D. B. ARCHER Table II Radiation retinopathy-a fluorescein angiographic study Follow-up Retinopathy Case No.
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