Comparison of Optical Coherence Tomography With Fundus Photographs, Fluorescein Angiography, and Histopathologic Analysis in Assessing Coats Disease

Abstract

Importance: Coats disease is a rare pediatric vitreoretinopathy that can cause devastating visual and anatomic outcomes.

Objective: To compare optical coherence tomography (OCT) with fundus photographs, fluorescein angiography (FA), and histopathologic findings in Coats disease.

Design, setting, and participants: This retrospective cohort study was conducted in a single tertiary institution (Duke Eye Center) and identified 28 children with Coats disease through a review of medical records from December 2002 to January 2018. Four eyes were obtained from a biorepository for histopathologic analysis.

Main outcomes and measures: Macular OCT, fundus photographs, and FA results were reviewed and compared for morphological changes. These were compared with retinal histopathological findings.

Results: The mean (SD) age was 9.5 (5.5) years for the 28 children (and 29 eyes) with clinical imaging results, and 24 (86%) were boys. A comparison between imaging modalities revealed OCT features that were not visible in photographs or FA, including exudates in multiple retinal layers (23 [82.1%]), small pockets of subretinal fluid (4 [14.3%]), an outer retinal atrophy overlying fibrotic nodules (7 [25.0%]), and small preretinal hyperreflective OCT dots (25 [89.3%]). Next, a comparison with light micrographs introduced an association of OCT findings with possible pathological features, including hyperreflective linear structures on OCT that appeared consistent with cholesterol crystals, small hyperreflective dots with macrophages, outer retinal tubulations with rosettes, and analogous OCT histopathology features such as intraretinal vessels entering fibrotic nodules and retinal pigment epithelium excrescences under the subretinal fluid. An OCT analysis revealed intraretinal cystoid spaces in 19 eyes, but in 9 of 19 (47.4) this was not associated with cystoid macular leakage; rather, fluorescein leakage was observed from peripheral telangiectatic vessels. Additionally, exudates were intraretinal only (6 [21.4%]) or both intraretinal and subretinal (17 [60.7%]); none were subretinal only. In eyes with follow-up results, new fibrosis developed in 8 of 17 eyes (47.1%). Fibrosis developed in 5 of 5 eyes (100%) with baseline subretinal fluid vs 3 of 12 without (25%; 95% CI, 22%-92%) and in 7 of 9 eyes (77.8%) with subretinal exudates vs 1 of 8 (12.5%) without (95% CI, 16%-89%).

Conclusions and relevance: Optical coherence tomography may show the transient and permanent effects of Coats disease on the retina. These results suggest that exudates and fluid in the macular subretinal space appear later in the disease and may result in fibrosis formation. Further studies are needed to confirm if early treatment could prevent vision-threatening macular fibrosis.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Ong receives grant support from the International Retinal Research Foundation. Dr Vajzovic reports receiving grant support from the Research to Prevent Blindness Unrestricted Grant to Duke Eye Center, Alcon, Roche, and Second Sight and personal fees from Alcon, DORC, Genentech, Jannsen, and Alimera Sciences. Dr Mruthyunjaya receives consulting fees from Optos. Dr Toth receives grant support from the National Institutes of Health (NIH) and royalties from Alcon. No other disclosures are reported.

Figures

Figure 1.. Exudates in Coats Disease

Fundus photograph (A) and optical coherence tomography (OCT) (B) from a 7-year-old boy. The OCT shows that exudates are found both intraretinally (yellow arrowheads) and subretinally (yellow arrow). The inset OCT demonstrates the presence of a subretinal fluid pocket (blue arrowhead) that is difficult to visualize on a 2-dimensional photograph. Low-power (C) and high-power (D) histopathologic staining with hematoxylin-eosin from an enucleated repository eye. On light micrographs, exudates appear as pinkish eosinophilic material in multiple intraretinal layers and subretinally (yellow arrowheads). The subretinal exudates are interspersed in subretinal fluid (blue arrowheads). Higher-power magnification demonstrates the presence of pigment and lipid-laden macrophages (white arrowheads) among exudates (yellow arrowhead) in the subretinal space. The vertical and horizontal white dotted lines on the photograph correspond with the main and inset OCT line scans, respectively, while the black dotted box on the low-power micrograph denotes the area shown in the high-power micrograph.

Figure 2.. Retinal Detachment in Coats Disease

Fundus photograph (A) and optical coherence tomography (OCT) (B) from a 7-year-old boy. C and D, Light micrographs with hematoxylin-eosin stain from 2 enucleated biorepository eyes. A comparison of OCT and light micrographs demonstrates corresponding structures, including hyperreflective linear cholesterol crystals (yellow arrowheads), retinal pigment epithelium excrescence (green arrowheads), and small intraretinal and subretinal hyperreflective dots in areas without exudates (white arrowheads) that may correspond with macrophages (white arrowheads) on light micrographs. Other OCT findings include subretinal fluid (blue arrowhead), exudates (yellow arrowheads), inner retinal wrinkling (brown arrowheads), small preretinal hyperreflective OCT dots (orange arrowheads), and the epiretinal membrane (pink arrowhead) are observed. The horizontal white dotted line on the photograph corresponds to the OCT line scan.

Figure 3.. Fibrotic Nodules With Intraretinal Rosettes in Coats Disease

A, OCT from a 4-year-old boy. Low-power (B) and high-power (C and D) light micrographs from an enucleated biorepository eye. A hyperreflective tubule with a hyporeflective core (green arrowhead) overlying exudates (yellow arrowheads) and a fibrotic nodule (red arrows) with subretinal fluid (blue arrowhead) is observed on OCT. This tubule appears to correspond to the intraretinal rosettes (green arrowheads) in the disorganized retina overlying the cholesterol granuloma on the high-power light micrograph (C). Other notable findings on light micrograph include a fibrous capsule surrounding the cholesterol granuloma (black arrowheads) as well as multinucleated giant cells with pigment granules (white arrowheads) surrounding cholesterol clefts (yellow arrowheads), proliferating capillaries (orange arrowheads), and fibrinous material (red arrowheads) within the cholesterol granuloma. The horizontal white dotted line in the inset photograph corresponds with the OCT line scan while the black dotted boxes on the low-power micrograph denote the areas above and within the cholesterol granuloma shown in the high-power micrographs

Figure 4.. Fibrotic Nodules With Intraretinal Vessels in Coats Disease

Fundus photograph (A) OCT (B) from a 7-year-old boy. Notable findings include retinal vessels diving into the lesion (white arrowhead), an adjacent dot of blood (pink arrow) on photograph, nodule (red arrowheads) with atrophy of overlying outer retinal layers, possible retinal vessels traveling at a right angle from the inner retina into the nodule (white arrowheads), and adjacent subretinal exudates (yellow arrowheads). Low-power (C) and high-power (D) light micrographs with a hematoxylin- eosin stain from an enucleated biorepository eye. A vessel traveling from the inner retina toward the nodule (white arrowhead) and multinucleated giant cells (black arrowheads) surrounding cholesterol clefts (yellow arrowheads) with a deposition of fibrinous material (red arrowheads) are observed on light micrographs. The horizontal white dotted line on the photograph corresponds to the OCT line scan while the black dotted box on the low-power micrograph (C) denotes the area shown in the high-power micrograph (D).

Figure 5.. Macular Intraretinal Cystoid Spaces in Coats Disease That Do Not Correspond With Angiographic Leakage

Fundus photograph (A), fluorescein angiography (FA) (B), and optical coherence tomography (OCT) (C) from an 11-year-old boy. There is no fluorescein leakage in the macula. The intraretinal cystoid spaces (blue arrowhead), subretinal fluid (blue arrow), and exudates observed on OCT are mostly located between the fovea (white arrowhead) and peripheral telangiectatic vessels that leak (pink arrowhead) on FA. The horizontal white dotted line on the photograph corresponds to the OCT line scan.