The exudative retinopathy of Coats is characterized by retinal vessel abnormalities, including thickening of the vessel walls, large aneurysms, and sausage-like beading. Retinal vessels in patients with this disorder have been examined in the pathology laboratory by a model of serial sections1 and electronmicroscopy,2 and in vivo utilizing fluorescein angiography.3 The etiology of the vessel changes is unknown. It is the purpose of this report to describe the histologic appearance of flat preparations of the retinal vessels in Coats' disease in order to better understand the distribution of vessel abnormalities and the changes in the vessel walls.
MATERIAL AND METHODS
Ten eyes with Coats' disease which were received at the Stanford Eye Pathology Laboratory from 1962 to 1974 were reviewed. The pathological diagnosis of Coats' disease was made from routine cross sections on the basis of an exudative retinal detachment with eosinophilic, periodic acid-Schiff (PAS) positive exudates around retinal vessels, in the outer retina and beneath the retina. The subretinal exudates contained clumps of large pale staining histiocytic cells and cholesterol clefts. Dilated retinal vessels were seen in all cases, although in some the dilation was slight The eyes had been enucleated with the presumptive diagnosis of Coats' disease, retinoblastoma, or metastatic uveitis. All the patients were male; the disease was unilateral in all cases. The age range was seven months to 13 years; eight patients were under three years old.
The eyes were sectioned horizontally and the center ring embedded in paraffin for routine cross sections. The remaining culottes were stored in 10 percent formalin. Retina for flat preparation was taken from these culottes. Additional retina was obtained by melting the paraffin embedded material. This method allowed almost the entire retina to be studied on flat preparation after the diagnosis had been made on the cross sections. Flat preparations of the retina were made by the trypsin digestion technique of Kuwabara and Cogan 4 and stained with PAS reagent Normal eyes were examined by the same technique to insure that the paraffin embedding had not produced artifacts. Fig. 1 shows a deparaffinized, trypsin-digested equatorial retina of a normal autopsy eye which had been embedded in paraffin for one year. The capillary size and cellularity is normal. The eyes with Coats' disease were more difficult to prepare than the normal eyes because the subretinal exudate tended to adhere to the retina.
Trypsin digestion revealed characteristic vascular abnormalities of aneurysm formation and heavy PAS positive deposits in the walls of the vessels in all ten retinas. Consistent patterns of distribution throughout the entire retina were observed. In all cases studied, aneurysms of two types were noted. The first type was similar to microaneurysms found in other diseases such as diabetic retinopathy, venous thrombosis and hypertensive retinopathy (Fig. 2). A second type of microaneurysm formation consisting of numerous large microaneurysms, sacular swellings, and huge sausage-like or beaded out-pouchings formed the most striking feature and appeared characteristic of Coats' disease (Figs. 3, 4, 5). These larger aneurysms ranged from 50 to 350 microns with an average size of 100 to 200 microns, and were often situated on shunt vessels.
Fig. 1. Equatorial retina from a normal autopsy eye. This specimen had been embedded in paraffin for one year before digestion. The size and cellularity of the vessels appear normal. The inside length of the line represents 100 microns (periodic acid-Schiff X120).
Fig. 2. Retinal digest from a patient with Coats' disease. Dilated capillaries with numerous small microaneurysms. The vessels are nearly acelluiar. The arterioles have a mottled PAS positive appearance (periodic acid-Schiff X120).
Intensely PAS positive material within the markedly thickened vessel wall was obvious in all cases, although there was variation in the number of vessels involved. It was common in the medium and large vessels, and less frequent in the capillaries. This exudate was dark even when the rest of the slide was understated by PAS reagent On the cross section this intramural deposit could be seen to be most prominent in the peripheral retina, and was associated with lakes of exudation in the outer retina
Fig. 3. Huge aneurysms and sausage- like beading of vessels. The dark areas represent PAS positive deposits (periodic acid-Schiff X44)
Fig. 4. Large sacular aneurysms with hypocellular walls. Capillary dilatation and acellularity are present as well as fibrous strands (periodic acidSchiff X120).
Fig. 5. Irregular vascular channels which replace the capillary network and act as shunt vessels. There are beading, dilatation, and aneurysms. The vessel walls are dark because of heavy accumulations of PAS positive material. The large vessels on the left and right of the figure were identified as a vein and artery respectively on different areas of the preparation (periodic acidSchiff X70).
Capillary dropout, fibrous strands, acellularity of vessel walls, and perivascular pigmentation were additional findings. These changes have been reported in many retinal diseases5"7 and would not seem to be related to Coats' disease per se. A characteristic cellular abnormality was not found. Hypocellular vessels did not show a predominant loss of either endothelial cells or mural cells.
A review of the routine cross sections revealed interesting associated findings in two eyes. In addition to the characteristic features of Coats' disease, these eyes showed coarse fibrils and small vessels in the vitreious cavity suggestive of persistent primary vitreous. One also had posterior migration of the lens epithelium and a microscopic break in the posterior lens capsule without fibrous invasion of the lens cortex. Both eyes had detachment of the nonpigmented ciliary epithelium and elongated ciliary processes.
The question of whether the exudative retinopathy described by George Coats * is really a disease entity or rather a syndrome with multiple etiologies as suggested by Duke-Elder* has not yet been answered. However, the similarity of the vascular abnormalities in all ten of our cases, and the differences between these changes in other exudative retinopathies, such as diabetes or hypertension, does point to Coats' disease being a true entity.
The combination of large aneurysms and vessel wall thickenings by a PAS positive material seems to occur characteristically in Coats' disease. These findings may occur individually in other conditions: increased staining of the arteriolar wall has been reported in ocular injury with retinal detachment, and systemic hypertension 6.7; large aneurysms and rows of bead- 1 ike outpouchings have been found in glaucoma.8'10 Hence, we cannot be absolutely certain that the retinal vascular abnormalities we have described are associated purely with Coats' disease, since all of our cases also had retinal detachment, and some had secondary glaucoma
We found no areas of normal retina in the eyes we studied, yet clinically Coats' disease can frequently present with sector retinal involvement. The areas of uninvolved retina can later become abnormal. Morales 11 followed 22 cases of untreated segmental Coats' disease for an average of five years and 12 showed progression into previously normal areas. One progressive case had been stable for eight years. Egerer et al 3 described the treatment of incomplete cases with disappearance of the exudate; however, they observed the appearance of new abnormal exudates two to five years later in three cases. It seems possible that all the retinal vessels possess an inherent defect which expresses itself at a variable age.
The question of pathogenesis is of great interest and takes two different directions. First, the dilated retinal vessels and aneurysms could be a congenital abnormality associated with increased vascular permeability; or secondly, it is possible that the increased permeability is the primary defect and the aneurysmal abnormalities are secondary changes. This latter hypothesis has been advanced by Tripathi and Ashton, who found endothelial defects in the retinal vessels of an early case of Coats' disease.2 Our observations do not allow us to choose between these two alternatives.
We do, however, present evidence in favor of a congenital origin of the defect First, the disease occurs in an advanced stage in early life - eight of our ten cases had enucleation at age three years or younger. Secondly, two of the ten eyes examined showed incomplete retinal and vitreous differentiation demonstrated by areas of persistent primary vitreous. In one of these there was a microscopic rupture of the lens capsule. These pathologic findings resemble the syndrome of persistent hyperplastic primary vitreous which is an established unilateral congenital anomaly.
Flat preparations of the retina were prepared by trypsin digestion in ten cases of Coats' disease. All of the patients were young males with advanced disease leading to enucleation. All eyes showed marked abnormalities in the arterioles, venules, and capillaries. The findings most characteristic of Coats' disease were large aneurysms and thick PAS positive deposits in vessel walls. The aneurysms ranged from 50 to 350 microns and frequently formed large sausage-like or beaded outpouchings and were sometimes situated on shunt vessels. Other findings frequently seen, but not specific for Coats' disease, were capillary dilatation, small aneurysms, hypocellular vessel walls, and fibrous strands.
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