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. Eye Initial angiographic findings Final angiographic findings period grade

R Small area, irregular capillaries 2 Large single microaneurysm increased 32 months microaneurysms. Focal capillary capillary irregularity, further capillary closure closure 2 R Focal capillary dilatation and closure, Increased area capillary dilatation and 31 months micro aneurysms and intra retinal number of microancurysms. Fusiform haemorrhages. Focal RPE changes capillary loops further capillary fallout. No vascular incompetence L Focal macular and perimacular inner Incomplete reperfusion ischaemic 58 months retinal ischaemia, intraretinal retina, absorption haemorrhage. haemorrhage, widespead capillary Development telangiectatic-like dilatation, distortion and channels. Macular oedema incompetence. Multiple ffilcroaneurysms 3 R Widespread capillary defects 1 RMA, 4 microaneurysms and inner retinal ischaemia superior retina. Arteriolar and venular occlusion. 4 L Dilated irregular incompetent Slight increase extent capillary \3 months 2 capillaries. Microaneurysms, capillary abnormalities and microancurysms. closure, RPE scar, inferior macula Dye leakage and retinal staining more intense 5 R Extensive inner retinal ischaemia, 3 IRMA, patent and thrombosed microaneurysms. Macular RPE changes, subretinal neovascularisation 6 R Dilated, disorganised macular 3 capillaries. Microaneurysms IRMA, telangiectatic-like vessels, cystoid macular oedema, retinal ischaemia 7 R Dilated, irregular capillaries. Multiple Further capillary closure, thrombosis 37 months 2 microaneurysms, capillary closure and and formation microaneurysms staining of defective capillary bed, increased dye leakage retinal oedema L Scattered dilated and incompetent Small increase in micro aneurysms and 38.5 months 2 caps, focal leakage of dye into retina. area of vascular staining and Microaneurysms and focal capillary incompetence closure 8 L Dilated telangiectatic like capillaries, Further closure capillary bed, 17 months 3 microaneurysms, focal retinal reperfusion of some radicals within ischaemia ischaemic retina 9 R Dilated, incompetent capillaries, 3 microaneurysms, choroidal vascular stasis, macular oedema 10 R Telangiectatic-like vessels, Extension of microvascular 14 months 3 microaneurysms cystoid macular abnormalities, increased capillary oedema. Retinal ischaemia. Venular incompetence. Some reperfusion of and arteriolar staining ischaemic retina 11 R Widespread capillary closure, IRMA's Further closure of abnormal dilated 28 months 4 and telangiectatic-like channels. capillaries, additional haemorrhages Irregular arterioles and venules, and increased microvascular leakage macular oedema L Dilated telangiectatic capillaries. Additional microaneurysms increased 2 Microaneurysms, early leakage microvascular incompetence capillary closure 12 L Microaneurysms focal RPE defects Gross macular oedema, ischaemia, 11 months 4 staining venules and arterioles R Microaneurysms small foci, Further microaneurysms, increased 2 incompetent, occluded vessels microvascular leakage \3 R Moderate background diabetic Intensification of retinopathy, increased 9 months 2 retinopathy. Focal capillary closure and capillary leakage leakage L Microaneurysms, capillary leakage Increased micro aneurysms and dye 2 leakage 14 R Telangiectatic-like macular vessels, 3 microaneurysms, focal capillary closure macular oedema 15 L Telangiectatic-like channels, extensive 4 retinal ischaemia, preretinal neovascularization

* RPE Retinal pigment epithelium, IRMA [ntraretinal microvascular abnormality. FLUORESCEIN ANGIOGRAPHIC FEATURES 661

marily due to the metabolic or radiational insult, although it is likely that it was a response to the combined or synergistic effects of radiation, chemotherapy and diabetes.

Grade 3 Retinopathy Seven eyes in this group were characterised by widespread capillary dilatation, telangiec­ tatic-like channels, microvascular incompe­ tence and significantareas of capillary closure (1-4 disc areas). All patients ha� significant macular oedema with or without cystoid mac­ ular degenerative changes (Fig. 4). Micro­ aneurysms and intra retinal microvascular abnormalities commonly occurred at the bor­ der of perfused and non-perfused retina. Eyes Fig. 1. Venous phase angiogram right posterior in this group typically had poor visual acuity, fundus, Case 3. Ischaemic retinopathy is largely i.e. five eyes had vision of 6/18 or worse. One confined to the irradiated superior fundus. patient in this group was diagnosed a diabetic diabetes mellitus one year prior to receiving six years following radiation to the right orbit radiotherapy and chemotherapy for a naso­ (Case 10). The retinopathy was severe and pharyngeal tumour. It was not possible to unilateral and was judged to be primarily radi­ determine whether the retinopathy was pri- ational in type, although the metabolic

Fig.2a. Mid-venous phase angiogram, right posterior fundus, Case I. Capillary irregularities and microaneurysms in the superior macula (arrows) represent early radiational changes. Retinal pigment epithelial changes are present at the foveola. Fig. 2b. Angiogram right fundus, Case 1, 32 months after that shown Fig. 2a. There is evidence of capillary fusion and closure. The wall of a dilated fusiform capillary stains with dye (arrow). 662 W. M. K. AMOAKU AND D. B. ARCHER

Fig. 3a. Venous-phase angiogram right posterior fundus Case 7. The macular microvascu{ature is grossly dilated and displays multiple microaneurysms of varying size. Small foci of capillary nonperfusion are evident. Fig.3b. Late phase angiogram of fundus shown Fig. 3a. Many dilated channels and microaneurysms stain and leak fluorescein into the nearby retina. Fig.3c. Venous-phase angiogram of fundus shown Fig. 3a, taken 37 months later. There is extension and intensification of retinopathy with capillary remodelling and appearance and disappearance of microaneurysms. The area of nonperfused retina has increased. Fig. 3d. Late phase angiogram of fundus shown Fig. 3c. Dye leakage has increased compared with Fig. 3b. FLUORESCEIN ANGJOGRAPHIC FEATURES 663

Fig. Je. Venous phase angiogram following laser photocoagulation to fundus, shown above, 2 months after angiograms Figs. 3c and d. Some defective capillaries are occluded and others reduced in calibre. Microaneurysms are reduced in number. Fig. 3r. Late phase angiogram, fundus shown Fig. 3e. Dye leakage is reduced except at one untreated area superonasal to foveola. This was subsequently treated. abnormality may have been a contributory factor.

Grade 4 Retinopathy Four eyes demonstrated widespread dis­ organisation of the retinal microvasculature with extensive inner retinal ischaemia. Non­ perfused retina was in excess of four disc areas, and one eye in this group developed preretinal neovascularisation and vitreous haemorrhage (Fig. 5). Two eyes with ischaemic maculopathy had visions of 6/60 and 3/60; however, two eyes with retinal ischaemia eccentric to the fovea retained vision of 6/6 and 6/12. Two patients in this group were diabetic and documented as having early background dia­ betic retinopathy prior to radiotherapy (Cases 3 and 12). The development of exten­ sive ischaemic retinopathy in each case after Fig.4a. Mid-venous phase angiogram left 'posterior radiotherapy reflects the combined microvas­ fundus (Case 2). There is advanced radiational retinopathy with focal areas of retinal nonperfusion, cular insult of the two disease processes. The dilated and incompetent capillaries, and intraretinal effects were particularly severe in case 12 haemorrhage. 664 W. M. K. AMOAKU AND D. B. ARCHER

area of microvascular non-perfusion using image analysis of high-quality angiograms. Over a period of three years this patient demonstrated a 50% nett increase in the number of micro aneurysms and a 70% nett increase in the area of non-perfused retina in spite of a considerable turnover in the number of microaneurysms, and abortive attempts at revascularisation of ischaemic retina (Fig. 3a and 3c). Three eyes followed in this study suffered loss of central vision concomitant with advancement of retinopathy, intra retinal fluid accumulation and macular ischaemia.

3. Treatment Two patients in the present study received argon (green) laser photocoagulation for Fig.4b. Venous phase angiogram fundus shown Fig.4a, 18 months later. There is some reperfusion of severe or advancing maculopathy associated ischaemic retina and development of incompetent with deterioration of vision. Focal laser telangiectatic-like channel over much of the nasal and photocoagulation was applied to areas of superior macula. deformed and incompetent capillaries and regions of non-perfused retina (Fig. 3e, f). where radiotherapy for a left lacrimal sac car­ Both patients showed improvement in visual cinoma resulted in severe ischaemia of the acuity (Case 7, 6/18 to 6/9) (Case 10, 6/36 to posterior retina at nine months and rubeosis 6/12-2) within two to three months of therapy, iridis within twelve months of treatment. and improvement was maintained at one year 2. Sequential study of radiation retinopathy post treatment in each case. All nine patients (14 eyes) followed sequen­ Post-treatment angiography revealed that tially in this study demonstrated intensifica­ some deformed and telangiectatic vessels tion and extension of retinopathy. No patient adjacent to photocoagulation burns collapsed demonstrated any reversal of pathology or improvement in retinal microvascular com­ petence, although attempts to recanalise non­ perfused capillary beds were occasionally observed (Fig. 4). The progression of micro­ vascular pathology varied in degree and extent (Table II), although the rate of change was typically slow, and in this series only one patient showed sufficient deterioration in the capillary bed to be regraded (Case 7, Fig. 3). Over the period of observation all patients showed additional capillary closure and a net increase in the number of micro aneurysms. In some eyes there was clear evidence of micro­ aneurysm thrombosis and atrophy. All patients in groups 2 to 4 showed more micro­ vascular incompetence with time as judged by the intensification of macular fluorescence in Fig. 5. Late venous phase angiogram of inferonasal late phase angiograms. In one patient fundus (case 15). There are multiple microaneurysms, (Case 7) it was possible to quantify some of extensive inner retinal ischaemia and a hyperfluorescent the retinal vascular changes and estimate the preretinal neovascular membrane. FLUORESCEIN ANGIOGRAPHIC FEATURES 665 and failed to perfuse with dye. Other dilated most accurately in patients undergoing radio­ capillaries were dramatically reduced in therapy for extraocular tumours and orbital calibre, and demonstrated increased compe­ disease, e. g. lymphoma and Grave's Disease, tence to fluorescein. Some micro aneurysms as radiotherapy of intraocular tumours intro­ either decreased in size or disappeared, and in duces not only the impact of ionising radiation some instances became less permeable to dye on the retinal vessels but also the secondary (Fig. 3e, f). Photocoagulation did not result in effects of the tumour and its postradiational any observable reperfusion of ischaemic ret­ necrotic products on the retinal neuropile and ina. One patient with widespread retinal microvasculature. Brachytherapy for intra­ ischaemia, preretinal neovascularisation and ocular tumours also causes local obliteration vitreous haemorrhage was advised to have of the choroidal circulation3,8,9,10 and pro­ laser therapy but declined treatment. found alterations in the nearby retinal pig­ ment epithelium3,9 which may influence the Discussion form and function of the nearby retinal Radiation retinopathy subsequent to both microvasculature. brachytherapy and teletherapy has been the This study was successful in identifying subject of fluorescein angiographic investiga­ early radiation retinopathy and monitoring tion by several workers. The early studies of the development of microvascular changes as Chee,1 Gass2 and Hayreh3 demonstrated that a large number of patients receiving substan­ all components of the retinal microvascula­ tial ocular radiation were screened and a sig­ ture could be affected, and that angiography nificant proportion of these had early was useful in identifying microvascular path­ pathology. Furthermore, some patients with ology and demonstrating changes in vascular bilateral retinopathy had advanced disease in perfusion and competence. Subsequent one eye but only early or incipient changes in angiographic investigations have also con­ the fellow eye which were particularly suit­ firmed that the outer retina and choroidal cir­ able for angiographic analysis. Also, in most culation could be implicated in the disease patients radiotherapy was successful in con­ process, and that photocoagulation could taining the primary malignant disease process limit some of the sight-threatening complica­ thereby facilitating long term observation. tions of end-stage retinopathy.4,5,6,7,16,17 The earliest identifiable changes of radi­ The progressive nature of radiation retino­ ation retinopathy (Grade 1) were focal capil­ pathy has been emphasised; however, the lary closure and irregular dilatation of the natural course of clinical radiation retino­ neighbouring microvasculature. The affected pathy is still poorly understood, largely due to vessels were typically competent in early the difficulties encountered in mounting disease although their walls often stained with longitudinal studies in patients who are often dye in late angiography. Retinal oedema was ill, who have a poor life expectancy, and who not a feature and visual functions were not occasionally develop corneal and lens opac­ measurably affected. With time, further local­ ities limiting observation of the ocular fun­ ised collapse of the capillary bed occurred, dUS.18 The long latent period between with development of additional dilated irradiation and development of retinopathy irregular capillaries. These dilated and telan­ and the typically slow progression of micro­ giectatic-like vessels probably represent capil­ vascular changes also make sequential analy­ lary collaterals which divert blood from sis of the vasculopathy difficult and hinder defunct microvascular units. prospective investigations. Furthermore, as The precise aetiology of capillary closure is early microvascular pathology is not usually unknown, however, it is likely that ionizing associated with significant loss of vision, radiation directly affects vascular endothelial patients with early retinal changes are cell viability or its potential to replicate, and unlikely to be identifiedunless screening pro­ the subsequent failure of the capillary endo­ cedures are instituted. thelium precipitates platelet deposition, cap­ The retinal microvascular alterations illary thrombosis and focal atrophy of the induced by ionizing radiation are observed retinal microvasculature.3,5,7,14 Microaneu- 666 W. M. K. AMOAKU AND D. B. ARCHER rysms were also a feature of early retinopathy Angiographic evidence of choroidal closure and typically formed in dilated capillaries or atrophy has mostly been described in which bordered perfused and non-perfused patients having radioactive plaque therapy for capillary beds. Their formation may be due to choroidal melanomas and retinoblasto­ the effects of a local increase in intra-luminal mas7,9,1O. The only angiographic changes in the pressure on channels which have been struc­ choroid following teletherapy were noted by turally compromised by the loss of either Thompson et at. 6 who described delayed chor­ endothelial cells or pericytes. oidal filling in patients receiving radiation for As early radiation retinopathy advanced, a nasopharyngeal tumours. Choroidal vascular significant part of the capillary bed, usually stasis, however, was only encountered in including the macula, became involved hypertensive patients and was not attributed (Grade 2). Dilated, tortuous and fusiform specifically to radiation damage. The present capillaries were the principal angiographic study has demonstrated angiographically that feature and microvascular incompetence the choroidal circulation can be compromised occurred as judged by fluorescein leakage. by gratuitous external beam irradiation of the Despite the presence of dye leakage, intraret­ eye, and that subretinal neovascularisation inal accumulation of fluid was often not pro­ may occur in association with radiational ret­ nounced and central visual functions were inopathy. Whether any causal relationship frequently surprisingly good despite involve­ exists between choroidal neovascularisation ment of the macular and perifoveolar circula­ and radiotherapy is not known; however, tions. The absence of clinically discernible degenerative changes induced in the retinal intraretinal fluid accumulation is probably a pigment epithelium and outer retina by radi­ measure of the efficiency of neighbouring ation may encourage the development of sub­ intact capillaries and local retinal pigment epi­ retinal neovascularisation particularly in thelium in dehydrating the affected retina. ageing patients with evidence of drusen Further progression of retinopathy is formation. characterised by the closure of additional cap­ This study has confirmed that laser photo­ illary beds, formation of intraretinal micro­ coagulation can have a beneficial effect on vascular abnormalities18 and the development radiation-induced maculopathy and suggests of additional micro aneurysms (Grade 3). A that patients who benefit most from photo­ quantitative analysis of such effects in one coagulation are those with early to moderate patient revealed that the number of micro­ macular oedema, without cystoid degener­ aneurysms doubled in three years and that the ative changes and who retain moderate visual area of capillary-free retina also increased by functions, i.e. 6124 or better. Kinyoun et at.16 a factor of about two. More generalised and others6,17,19 have noted that laser photo­ microvascular incompetence was associated coagulation not only has a positive effect on with clinically evident retinal oedema, and radiational maculopathy but also serves to where the foveola was implicated, visual func­ contain or eliminate preretinal and papillary tions declined sharply. neovascularisation, thereby reducing the inci­ End stage radiation retinopathy (Grade 4) dence of vitreous haemorrhage and retinal is characterised by generalised microvascular detachment. disorganisation, inner retinal ischaemia and The mechanism whereby laser photocoag­ capillary incompetence often leading to cys­ ulation improves retinal vascular competence toid macular oedema. The degree of inner is not known, although this study and others retinal ischaemia in Grade 4 eyes may be suf­ confirm that judicious photocoagulation ficient to promote preretinal neo­ effectively occludes and ablates some incom­ vascularisation. Other authors have also petent capillaries and microaneurysms. This described papillary neovascularisation,6,18,19 study also demonstrates that laser photocoag­ vitreous haemorrhage,16,19 retinal detach­ ulation indirectly reduces the calibre of ment, rubeosis iridis and secondary glaucoma dilated and deformed capillaries, possibly by in such eyes which usually have received high diminishing cell density in the outer retina in doses of ocular radiation.16,19 the vicinity of the affected microvasculature.20 FLUORESCEIN ANGIOGRAPHIC FEATURES 667

Theoretically the depopulated and attenuated ation retinopathy following treatment of pos­ retina will have lower metabolic requirements terior nasal space carcinoma, Br J Ophthalmol 1983, 67: 609-14. and may permit better oxygenation of the 7 Ehlers N and Kaae S: Changes in radiation treated inner retina and its vascular cells from the retinoblastoma and radiation effects in the choroidal circulation.21,22 Photocoagulation normal ocular fundus. Acta Ophthalmol 1987, burns may also create defects in the retinal SuppI181,65:32-62. 8 pigment epithelial layer, producing conduits Lommatzsch P: Beta-irradiation of choroidal melan­ oma with 106 RuJ106 Rh applicators. Arch Oph­ which facilitate the drainage of excess retinal thalmol1983, 101:713-7. fluid into the choroidal circulation.23 Alter­ 9 Lommatzsch PK, Ballin RE, Helm W: Fluorescein natively, it could be argued that, following angiography in the follow-up study of choroidal laser photocoagulation, the rejuvenated ret­ melanoma after 106 RuJ106 Rh plaque therapy. Retina1987, 71:148 -155. inal pigment epithelium has more effective IO Tarkkanen A and Laatikainen L: Fluorescein pumping properties and is consequently able angiography in the long-term follow-up of chor­ to dehydrate the oedematous retina. Never­ oidal melanoma after conservative treatment. Acta Ophthalmol198 5, 63: 73 -9. theless, irrespective of the mechanism 11 Wara WM, Irvine AR, Neger RE et al.: Radiation whereby laser photocoagulation improves retinopathy. Int J Radiat Oncol BioI Phys19 75,5: microvascular function in radiational retino­ 81-3. pathy it is clearly an important therapeutic 12 Irvine AR, Alvarado JA, Wara WM et al.: Radiation tool, particularly in early maculopathy and retinopathy:. an experimental model for the ischaemic-proliferative retinopathies. Trans Am vasoproliferative disease. Accordingly, we Ophthalmol Soc1981, 79:103-20. would suggest that patients receiving in excess 13 Martin H and Reese AB: Treatment of bilateral ret­ of 3,000 cGy to the eye should be regularly inoblastoma (retinal glioma) surgically and by reviewed and that patients receiving greater irradiation. Arch Ophthalmol1945, 33: 429-38. than 5,000 cGy to the eye should be closely 14 MacFaul PA and Bedford MA: Ocular complica­ tions after therapeutic irradiation. Br J Ophthal­ observed. Ophthalmologists should also liaise mol 1970, 54: 237-47. with radiotherapists carrying out cephalic 15 Noble KG and Kupersmith MJ: Retinal vascular radiation, particularly to patients with naso­ remodelling in radiation retinopathy. Br J Oph­ pharyngeal and paranasal sinus tumours, both thalmoI198 4, 68: 47 5- 8. 16 Kinyoun JL, Chittum ME, Wells CG: Photocoag­ to acquaint the radiotherapist regarding the ulation treatment of nidiation retinopathy. Am J likelihood of radiation retinopathy and to Ophthalmol198 8,105: 47 0- 8. encourage where possible effective screening 17 Chaudhuri PR, Austin DJ, Rosenthal AR: Treat­ of the eye during treatment of these malignant ment of radiation retinopathy. Br J Ophthalmol 1981,65: 623-5. tumours. 18 Amoaku WMK and Archer DB: Cephalic radiation and retinal vasculopathy. Eye1990, 4:195-203. 19 Parsons JT, Fitzgerald CR, Hood CI et al.: The effects of irradiation of the eye and optic nerve. References Int J Radiat Oncol BioI Phys 1983, 9:609-22. 1 Chee PHY: Radiation retinopathy. Am J Ophthal­ 20 Marmor MF: Clinical physiology of the retina. In: mol 1968, 66: 860- 5. Principles and Practice of Ophthalmology. Eds: 2 Gass JDM: A fluoresceinangiographic study of mac­ Peyman GA, Saunders DR, Goldberg MF. Phila­ ular dysfunction secondary to retinal vascular delphia, WB Saunders Co 1980, 823-856. disease VI. X-ray irradiation, carotid artery 21 Wolbarsht ML and Landers MB: The rationale of occlusion, collagen vascular disease and vitritis. photocoagulation therapy for proliferative dia­ Arch Ophthalmol1968 , 80: 606-17. betic retinopathy. A review and a model. Oph­ 3 Hayreh SS: Post-radiation retinopathy: A fluores­ thalmic Surg 1980, 11:235-45. cence fundus angiographic study. Br J Ophthal­ 22 Landers MB, Stefansson E, Wolbarsht ML: Panret­ mol 1970, 54:705-14. inal photocoagulation and retinal oxygenation. 4 Bagan SM and Hollenhorst RW: Radiation retino­ Retina1982,2: 167-75. pathy after irradiation of intracranial lesions. Am 23 Golbaum MH: Photocoagulation: Theory and Prac­ J Ophthalmol1979, 88:694-7. tice. In: Principles and Practice of Ophthal­ 5 Brown GC, Shields JA, Sanborn G et al.: Radiation mology Vol II. Eds: Peyman GA, Saunders DR retinopathy. Ophthalmol1982 , 89:1494-50 1. and Goldberg MF. Philadelphia. Saunders WB 6Thompson GM, Midgal CS, Whittle RJM: Radi- Co 1980, 1098-1122.