Journal of Pediatric Ophthalmology and Strabismus

Coats' Disease: A Study of 62 Histologically Confirmed Cases

Meimei Chang, MD; Ian W McLean, LTC, MS, USA; John C Merritt, MD

Abstract

SUMMARY

We studied 62 eyes submitted to the Armed Forces Institute of Pathology (AFIP) from 1958 through 1980 that satisfied our criteria for the histologie diagnosis of Coats' disease. Our histopathologic definition of Coats'disease was the presence of a primary vascular lesion consisting of retinal telangiectasia with leakage of plasma toform intraretinal and subretinal exuda t es. In the cases we reviewed, Coats' disease occurred more frequently in boys, it usually affectedonly one eye, and wasgenerally detected in the first decade of life. In 52 cases (79%) theclinical manifestations, strabismus and leukokoria, were thought to be caused by retinoblastoma. Angle closure glaucoma was present in 36 cases (58%). In all but one of the cases studied, the lesion waslocated peripheral to theequator. We further identified diffuse involvement of capillaries in the peripheral retina using trypsin-digest preparations. Associated histologie findings included: rubeosis iridis, cataract, vitreous neovascular ization, and nodules resulting from fibrous metaplasia of the retinal pigment epithelium. These fibrous nodules typically occurred in the macular area and occasionally contained calcium or bone.

Abstract

SUMMARY

We studied 62 eyes submitted to the Armed Forces Institute of Pathology (AFIP) from 1958 through 1980 that satisfied our criteria for the histologie diagnosis of Coats' disease. Our histopathologic definition of Coats'disease was the presence of a primary vascular lesion consisting of retinal telangiectasia with leakage of plasma toform intraretinal and subretinal exuda t es. In the cases we reviewed, Coats' disease occurred more frequently in boys, it usually affectedonly one eye, and wasgenerally detected in the first decade of life. In 52 cases (79%) theclinical manifestations, strabismus and leukokoria, were thought to be caused by retinoblastoma. Angle closure glaucoma was present in 36 cases (58%). In all but one of the cases studied, the lesion waslocated peripheral to theequator. We further identified diffuse involvement of capillaries in the peripheral retina using trypsin-digest preparations. Associated histologie findings included: rubeosis iridis, cataract, vitreous neovascular ization, and nodules resulting from fibrous metaplasia of the retinal pigment epithelium. These fibrous nodules typically occurred in the macular area and occasionally contained calcium or bone.

Coats1·2 described a childhood exudative retinopathy, occasionally present at birth, for which the primary feature was hemorrhage and exudation from retinal blood vessels into the subretinal space. Reese later described clinically and histologically, Coats' disease as a unilateral, exudative retinopathy resulting from telangiectasia of retinal vessels.3·4 The disease invariably appears before the age of eight and males are involved in most cases (78%). This report summarizes the findings of a large series of Coats' disease from the Armed Forces Institute of Pathology (AFIP).

Materials and Methods

We reviewed 150 cases on file in The Registry of Ophthalmic Pathology, submitted to the AFIP from 1958 through 1980, in which the final histopathologic diagnosis was Coats' disease. Histologie sections of the eyes were examined. Cases were selectedfor study according to histologiccriteria adapted from Reese: il I the presence of retinal telangiectasia, and (2) a highly characteristic intraretinal exúdate (Figure 1). The presence of hemorrhage, hemosiderin or retinal detachment was not necessary for inclusion in our study. Multiple factors including age, sex, race clinical symptoms a rid h is t o logic findings were analyzed to clarify our description of Coats' disease. All slides were reviewed by the senior authors.

Of thel50cases retrieved, only 62 m et ou r criteria. Cases were eliminated for the following reasons: inadequate sectioningor poor histologie preparation, cases where surgical intervention preceded enucleation, and cases with other pathologic process (e.g., retinal hemangi orna, massive gliosis, or a Coats'-like lesion secondary to concomitant intraocular disease).

Table

TABLE 1CLINICAL DIAGNOSIS IN EYES WITH COATS' DISEASE (62 CASES)

TABLE 1

CLINICAL DIAGNOSIS IN EYES WITH COATS' DISEASE (62 CASES)

Table

TABLE 2TIME INTERVAL FROM ONSET OF SYMPTOMS TO ENUCLEATION (62 CASES)

TABLE 2

TIME INTERVAL FROM ONSET OF SYMPTOMS TO ENUCLEATION (62 CASES)

Results

Coats' disease was the primary clinical diagnosis in only 13 of the 62 cases analyzed. The remaining cases were misdiagnosed as retinoblastoma in 36 (58%) and retinal detachment in 13 (21% ) (!able 1 ). The presenting signs and symptoms included strabismus (9 cases), leukocoria (17 cases), and both <8 cases).

In these 62 casesof Coats' disease, 43patients were male, 18 were female, and in one case the sex was not known; 33 patients were white, 18 were black, two were Indian, and one was oriental. The race of eight patients was not known. The right eye was involvedin 29 patients, and the left eye in 28 patients; both eyes were involved in one patient; and the eye involved was unknown in three patients.

In 51 cases, enucleation had been performed in patients under six years of age. In 90% of these cases, the onset of symptoms had been rapid (Table 2). Glaucoma was present in 37 of the eyes with Coats' disease, and treatment for this glaucoma had been instituted prior to enucleation in 12 cases. Glaucoma was secondary to angle closure, and, in one of the 62 cases was the glaucoma present in the uninvolved eye. In 17 glaucomatous eyes, the ocular tensions ranged from 21-60 mm Hg; though only one eye had pressure greater than 60 mm Hg. In only two eyes was the glaucoma known tobe controlled fol lowing any therapeutic interventions.

Histopathology: To satisfy study criteria, eyes included had retinal telangi ectasia and intraretinal exúdate (Figures 1-3). The degree of capillary dilation and aneurysmal formation varied. The telangi ectatic vessels were occasionally thrombosed. Periodic acid-Schiiï (PAS) stains which highlighted the presence of the telangiectatic vessels revealed that in these vessels the lumen was separated from the PAS-positive basement membrane by only a thin layer of endothelium. The intraretinal exúdate, characteristically very eosinophilic, stained PAS positive. The exúdate was confined to theouter retinal layers in21 cases, but occupied all Iayersin41 cases. The accumulati on of exúdate thickened the retina and separated nuclei in the naclear layer with varying degrees of retinal degeneration and gliosis. The esudate which accumulated under the retina had the same staining characteristics as the intraretinal exúdate. Scattered pale-staining histiocytes with or without phagocytosed melanin granules were present in the subretinal exúdate. The intraretinal exúdate contained a few extravasculated erythrocytes in 90% of the cases. In only one case was there hemorrhage great enough to be appreciated with low-power microscopy. Minimal accumulation of hemosiderin was noted in nine cases. The retinal telangiectasia occurred in the periphery in all but one eye. In that eye it was found near the equator. No telangiectatic lesions were demonstrated in the posterior pole.

The most common findings in the portions of retina not affected by telangiectasia were atrophy and gliosis of the outer retinal layers (45 cases) (Figure 4). Atrophy of all layers was present in 13 eyes, all of which had associated long-standing glaucoma. The retinal architecture was relatively normal in only four eyes. Microcystic degeneration occurred in 81% of the eyes (Table 3). Rosettes formed by folding of the detached retina were found in 35 eyes. A mud, chronic retinal peri vascu lit i s was notedin 28 eyes (Figures 4 & 5). Flat-tryps in -digest preparations of retinal vessels5 have revealed a more diffuse involvement of all peripheral retinal capillaries than was apparent on rout ine h istologìe sections (Figure 6 & 7). The capillaries were hypocellular and demonstrated a greater loss of endothelial cells than pericytes (Figure 7).

FIGURE I: Lesion of Coats' disease consisting of retinal telangiectasia and intraretinal exúdate. Exúdate with numerous cholesterol clefts has collected beneath the detached retina. (Hernatoxylin and eosin, X2S. AFIP Neg. 81-192151.

FIGURE I: Lesion of Coats' disease consisting of retinal telangiectasia and intraretinal exúdate. Exúdate with numerous cholesterol clefts has collected beneath the detached retina. (Hernatoxylin and eosin, X2S. AFIP Neg. 81-192151.

FIGURE 2: Higher power view of lesion. Telangiectatic vessels are partially thrombosed, Intraretinal gliosis and exudation are present. (Hematoxylin and eoxin, X 60 AFIP Neg. 82- 7192!.

FIGURE 2: Higher power view of lesion. Telangiectatic vessels are partially thrombosed, Intraretinal gliosis and exudation are present. (Hematoxylin and eoxin, X 60 AFIP Neg. 82- 7192!.

FIGURE 3: Periodic acid-Schiff staining highlights of walls of the telangiectatic vessels. iPeriodic acid-Schiff, X 160. AFIP Neg. 81-19220.)

FIGURE 3: Periodic acid-Schiff staining highlights of walls of the telangiectatic vessels. iPeriodic acid-Schiff, X 160. AFIP Neg. 81-19220.)

FIGURE 4: Detached, highly folded retina away from the lesion with marked glioais of outer layers and retinal perivasculitis.iliematoxylin and eosin, X 60. AFIP Neg. 81-19217).

FIGURE 4: Detached, highly folded retina away from the lesion with marked glioais of outer layers and retinal perivasculitis.iliematoxylin and eosin, X 60. AFIP Neg. 81-19217).

A variable amount of exudative, non-rhegmatogenous ret ina !detachment was present inali ofthe eyes studied. In 37 eyes the subretinal proteinaceous exúdate contained cholesterol clefts and foamy histiocytes without granulomas. Cholesterol granulomas were noted in 20 eyes (Figure 5). Although pigment-lade n macrophage s were present in 58 eyes, they were abundant in only half of these eyes.

Retinal pigment epithelial abnormalities were present in 46 eyes; which included: drusen formation (11 eyes), hyperplasia (11 eyes), fibrous metaplasia (eight eyes), and bone formation (four eyes). Subretinal pigment neovascularization was observed in four eyes. In six eyes a fibrous nodule was present in the posterior pole or macular area that was occasionally calcified (Figure 8) or ossified (Figure 9}.

Table

TABLE 3HISTOLOGIC TYPES OF RETINAL DEGENERATION AWAV FROM THE PRIMARY LESION IN COATS' DISEASE (62 CASES)

TABLE 3

HISTOLOGIC TYPES OF RETINAL DEGENERATION AWAV FROM THE PRIMARY LESION IN COATS' DISEASE (62 CASES)

FIGURE 5: Cholesterol granuloma in the subretinal space. The detached retina isgliotic, and the retinal vessels are infiltrated with chronic inflammatory cells. (Hemataxylin and eosin, X 60). AfIP Neg. 81-19219.)

FIGURE 5: Cholesterol granuloma in the subretinal space. The detached retina isgliotic, and the retinal vessels are infiltrated with chronic inflammatory cells. (Hemataxylin and eosin, X 60). AfIP Neg. 81-19219.)

FIGURE 6: Trypsin-digest preparation of peripheral retina. Capillaries are involved diffusely with microaneurysms. (Periodic acidSchiffX 25. AFIP Neg. 82-80551.

FIGURE 6: Trypsin-digest preparation of peripheral retina. Capillaries are involved diffusely with microaneurysms. (Periodic acidSchiffX 25. AFIP Neg. 82-80551.

FIGURE 7: Try psin-digest preparation, of peripheral retina. Capillaries are hypocellular with saccular and sausage-like aneurysms. (Periodic acid-SckiffX 160. AFIP Neg. 82-8056).

FIGURE 7: Try psin-digest preparation, of peripheral retina. Capillaries are hypocellular with saccular and sausage-like aneurysms. (Periodic acid-SckiffX 160. AFIP Neg. 82-8056).

FIGURE 8: Calcium within the center of a fibrous nodule located beneath the macula. Retinal pigment epithelium has proliferated forming cords and duels within the nodule (arrows). (Hematoxylin and eosin, X 60. AFJP Neg. 81-19214).

FIGURE 8: Calcium within the center of a fibrous nodule located beneath the macula. Retinal pigment epithelium has proliferated forming cords and duels within the nodule (arrows). (Hematoxylin and eosin, X 60. AFJP Neg. 81-19214).

Retinal and vitreous membr anes infrequently occurred, though avascular retinal membranes were detected in 11 cases. These were preretinal (nine), subretinal (one), and periretinal (one). Neovascularization of the vitreous body was seen inlScases. The primary site was at theora serrata (Figure 10) in ten eyes, was preretinal in two eyes, and was located in both sites in one eye.

Secondary pathologic changes occurred in both the iris and the choroid. The following abnormalities were found in the choroid: hemorrhage (one eye), edema (four eyes), and edema plus detachment (one eye). A mild to moderately severe chronic non-gran u Io matous uveitis was noted in 48 of the 62 eyes. The iris was involved in four eyes, the choroid was involved in 13 eyes, and both were involved in 31 eyes. The iris was atrophie in ten cases. Rubeosis iridis with or without ectropion uvea was present in 42 eyes. This neovascularization caused peripheral anterior synechiae in 35 eyes; however, there was only focal involvement in nine eyes. Synechiae between the iris and lens were more difficult to evaluate histologically; but combined with the clinical description, they were found in 12 eyes. Cataracts, present in 15 eyes, resulted from cortical degeneration (five cases) or to posterior migration of the lens epithelium (tencases). No eyes contained a dislocated lens, though an anterior displacement of the lens-iris diaphragm was evident in six eyes.

The cornea was essentially normal in 56 cases (90%) with the exception of mild endothelial attenuation. Bullous keratopathy or stromal scarring secondary to glaucoma was noted in only six cases.

FIGURE 9: Osseous metaplasia (arrows) ivilhin the fibrous nodule located beneath the macula. A sheet of proliferated retinal pigment epithelium is present adjacent to the bone. (Hetnatoxylin and eosin, X 60. AFIP Neg. 81-1805S).

FIGURE 9: Osseous metaplasia (arrows) ivilhin the fibrous nodule located beneath the macula. A sheet of proliferated retinal pigment epithelium is present adjacent to the bone. (Hetnatoxylin and eosin, X 60. AFIP Neg. 81-1805S).

FIGURE 10: Scanty neovascularization al the ora serrata. (Hematoxylin and eosin, X 250- AFiP Neg. 81-18057).

FIGURE 10: Scanty neovascularization al the ora serrata. (Hematoxylin and eosin, X 250- AFiP Neg. 81-18057).

The optic nerve was abnormal in 16 cases demonstrating atrophy and gli osi s (12 eyes), giant drusen (two eyesl, hemorrhagic infarction (one eye), and cystic degeneration (one eye).

Discussion

The most commonly reported clinical presenting signs of Coats' disease have been leukokoria and/or strabismus (55% in our study). However, 11% of our patients presented with painful glaucoma of "sudden onset" due to angle closure. Histologie al Iy we foundahighpercentageof eyes with secondary involvement of the anterior segment structures. These included corneal changes (six cases), rubeosis iridis (42cases), iris atrophy (tencases), peripheral anterior synechiae (35 cases), cataract formation (15 cases), and mild nongranulomatous iritis (four cases).

The age at onset of symptoms has been reported to be between six and eight years;6-'3 however, there have been scattered case reports1^-17 and cases in our own series in which the ? ? set of symptoms occurred in children under six months of age. The predilection for males has been reported to be between 78% and 84% in clinical series. 6.7.13,15 Jn Our series, in which the diagnosis of Coats' disease was made and/or confirmed histologically, we found a slightly lower male preponderence ( 69% ).

Recently, increasing emphasis has been placed upon the bilateral occurrence of Coats' disease6,8-18,20 and its association with other systemic diseases as muscular dystrophy,19 retinitis pigmentosa,21 and Turner's syndrome. 22 Our study contained only one case of bilateral Coats' disease which occurred in a healthy child.

We concur with other authors6,7,13,23,'24 that the primary feature of Coats' disease is retinal tel a ngi ectasia with secondary intraretinal and subretinal exúdate and edema. Our histologie findings support observations by Manschott25 and others8-26-29 that intraretinal hemorrhages are not obligatory in the pathogenesis of Coats' disease. Using try ps i n -digest preparations, we found much more extensive involvement of the peripheral retinal capillaries than has been previously described.30 These capillaries hac numerous saceular and fusiform aneurysms with loss of vascular endothelial cells. Retinal telangiectasia was not present posterior to the equatorin any of our cases. Because we found no vascular abnormalities in the posterior pole, we conclude that the ex u date located posteriorly is a secondary finding.

In Coats' disease vascular anomalies have been observed in the posterior pole using fluorescein angiography. Egerer et al.15 found vascular lesions in the macular area in 24% of their cases. Their description of the vascular changes included abnormalities of small vessels (microaneurysms and capillary drop-out) as well as the larger dilated channels similar to those that we observed histologically. We suspect that although there may be small vessel disease in the macular area, the most severe disease with large dilated channels is located at the periphery.

Retinal telangiectasia should be distinguished from Coats' disease when it is confined to the macula and occurs without exúdate. This condition occurs in adults, while Coats' disease affects children. Utilizing fluorescein angiography, the staining pattern is different from that associated with Coats' disease. Similarly, Gass and Oyakawa32 described '"idiopathic juxtafoveolar retinal telangiectasis" different from Coats' disease.

Neo vascular i z at io n of the vitreous body has not been commonly described in cases of Coats' disease. In a few case reports,la-'ìs-3a neovascularizatiori of the vitreous was observed at the posterior pole. In our series, vitreous neovascularización occurred in 13 eyes (21%). In ten of these 13 eyes there were only a few delicate vessels present at the ora serrata (Figure 4). This may have led to the mild vitreous hemorrhage seen in six eyes. These vessels would be difficult to detect clinically, even by careful examination of the peripheral vitreous using either the three-mirror GoIdmann lene or by indirect ophthalmoscopy with scierai depression.

In our 62 cases, we observed a fibrous submacular nodule in 13 (21%) of the eyes at the posterior pole. These nodules were occasionally partially calcined (Figure 8) or ossified (Figure 9). Although their origin is uncertain, we believe they represent an exuberant proliferation and fibrous metaplasia of the retinal pigment epithelium (Figure 8), because cords of pigment epithelial cells were found within the nodules. No case in the present series revealed hemorrhage below the retinal pigment epithelium, a finding which might be expected if these nodules were disciform lesione.

References

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TABLE 1

CLINICAL DIAGNOSIS IN EYES WITH COATS' DISEASE (62 CASES)

TABLE 2

TIME INTERVAL FROM ONSET OF SYMPTOMS TO ENUCLEATION (62 CASES)

TABLE 3

HISTOLOGIC TYPES OF RETINAL DEGENERATION AWAV FROM THE PRIMARY LESION IN COATS' DISEASE (62 CASES)

10.3928/0191-3913-19840901-03

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