PMC9376321_01
Prominent dilated episcleral and conjunctival vessels were noted in both eyes without signs of rubeosis of iris or iridocorneal angle closure. OD, right eye; OS, left eye.
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F1
Slit-lamp biomicroscope examination revealed prominent dilated and tortuous episcleral and conjunctival vessels in both eyes (Figure 1).
Ultrawide-field color pictures and autofluorescence in both eyes. (A,B) Ultrawide-field color pictures showed mild retinal venous dilation without hemorrhages and numerous flecks with subtle yellow subretinal flecks surrounding the papillomacular region. (C,D) Fundus autofluorescence showed mild hypo-autofluorescence in the foveal center and marked hyper-autofluorescence of these flecks surrounding the optic nerve head and macular region in both eyes. In left eye, gravitational track was observed on fundus autofluorescence.
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F2
Ultrawide-field color picture (Optos 200Tx, United Kingdom) showed numerous flecks on retina in both eyes, especially in right eye, with subtle yellow subretinal flecks surrounding the macula and optic disc, as well as in the papillomacular region (Figures 2A,B). Retinal pigment epithelial mottling and atrophy in ring-like configurations in both eyes and optic nerve atrophy of right eye were also noticed (Figures 2A,B). Fundus autofluorescence using ultrawide-field imaging (Optos 200Tx, United Kingdom) showed mild hypo-autofluorescence in the foveal center and multiple irregular hyper-autofluorescent flecks with a constellation-like pattern surrounding the optic nerve head and macular region in both eyes (Figures 2C,D). In left eye, gravitational track was observed on fundus autofluorescence (Figure 2D). TOPCON, Japan) analysis was performed on both optic discs and macula. The results showed obvious optic nerve atrophy with decreased thickness of the peripapillary retinal nerve fiber layer and enlarged cup/disc ratio in right eye, and mild inferior atrophy of the optic nerve in left eye (Supplementary Figure 2A). There was 32% symmetry for retinal nerve fiber layer thickness between right eye and left eye; and as for the thickness of retinal nerve fiber layer, SS-OCT analysis showed that significant decrease in the thickness of retinal nerve fiber layer in right eye than that in left eye, i.e., 74 mum vs. 166 mum (total), 73 mum vs. 159 mum (superior), and 76 mum vs. 142 mum (inferior) (Supplementary Figure 2A). Disc topography of SS-OCT showed the decreased rim area and disc area, while increased cup/disc ratio and cup volume in right eye compared with that in left eye (Supplementary Figure 2A). Thus both retinal nerve fiber layer and disc topography analysis showed severe damage of the optic nerve in right eye than left eye (Supplementary Figure 2A). SS-OCT, the macular thickness analysis of inner retina was also demonstrated significantly thinner in right eye than that in left eye (Supplementary Figures 2B,C). SS-OCT analysis showed that the thicknesses were 61 mum (right eye) vs. 142 mum (left eye), 80 mum (right eye) vs. 115 mum (left eye), 142 mum (right eye) vs. 256 mum (left eye), respectively, for the total thickness of retinal nerve fiber layer, the total thickness of retinal nerve fiber layer and ganglion cell layer (+), and the total thickness of retinal nerve fiber layer, ganglion cell layer and inner plexiform layer (ganglion cell layer++) (Supplementary Figures 2B,C).
Marked cystoid macular edema with intraretinal fluid, subfoveal neurosensory retinal detachment and pachychoroid on OCTA b-scan in both eyes. OD, right eye; OS, left eye; SCP, superficial capillary plexus; DCP, deep capillary plexus.
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F3
Optical coherence tomography angiography (OCTA) (RTVue XR, Optovue Inc., Fremont, CA, United States) b-scan demonstrated chronic CSCR-like abnormalities in both eyes with both intraretinal and subretinal fluid accumulation, and choroidal thickening (Figure 3). The thickness of central retina was higher in left eye than that in right eye, i.e., 595 mum vs. 414 mum (Figure 3), both demonstrating intraretinal cystoid edema and subretinal fluid, without obvious pigment epithelial detachment. The vessel densities were also compared between both eyes, demonstrating less vessel densities in right eye than that in left eye in both SCP and DCP (Figure 3). The deterioration of visual fields in both eyes showed marked central scotoma in right eye than left eye (Supplementary Figures 3A,B). The visual field examination with perimetry showed the aggregation of visual field loss in right eye, while improvement in left eye (Supplementary Figures 3C,D).
Fluorescein angiography (FA) and indocyanine green angiography (ICGA) showed bilateral changes of retinal and choroidal vessels. Infrared (IR) image showed patched hypo-reflection in macula and hyper-reflective flecks surrounding the macula and optic discs in both eyes. Background autofluorescence (BAF) image showed patched hypo-autofluorescence in macula and hyper-autofluorescence flecks surrounding the macula and optic discs in both eyes. Both FA and ICGA showed delayed and slow perfusion of the retinal and choroidal vessels. The flecks were early blocking with late staining. FA showed macular leakage with pronounced cystoid macular edema, deep masking in the area of the choroidal detachment. ICGA showed dilation and congestion of the choroidal vessels, especially vortex veins, in both eyes. SD-OCT with the Heidelberg Spectralis showed cystoid macular edema with intraretinal fluid and subretinal fluid accumulation in both eyes. FA, fluorescein angiography; ICGA, indocyanine green angiography; IR, infrared; BAF, background autofluorescence; OD, right eye; OS, left eye.
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F4
FA and ICGA showed delayed perfusion and slow flow in both retinal and choroidal vessels (Figure 4). FA shows marked leakage of macula and optic nerve head with time, cystoid macular edema, early blocking with late staining of above flecks shown in the backgrounds of infrared (IR) and autofluorescence (BAF) in both eyes; as well as mild leakage in peripheral retina; while ICGA showed dilated and tortuous vortex veins without obvious leakage in early phase and mid-phase (Figure 4). SD-OCT with the SPECTRALIS Heidelberg showed cystoid macular edema with intraretinal fluid and subretinal fluid accumulation in both eyes (Figure 4). FA and ICGA, the images of four quadrants including superior, nasal, inferior, and temporal were taken (Supplementary Figure 4). FA results showed that the peripheral retina vessels, especially the temporal to the fovea, were dilated with leakage over time; and ICGA demonstrated the dilation, tortuosity and congestion of choroidal vessels, which was more obvious for the vortex veins (Supplementary Figure 4).