PMC8249001_01
Multimodal imaging of ritonavir toxic maculopathy (patient 1). Top row:Initial examination of fundus showed discrete macular atrophy of granular appearance (A). A wider extent of maculopathy was best demonstrated by pseudo-infrared photography (B), which very precisely delineated borders of maculopathy. Autofluorescence fundus photography (C) was somehow less informative than pseudo-infrared technique. Second row:Retinal fluorescein angiography showed a mottled hyperfluorescent appearance of left macula, from early phase on (D), without leakage in intermediate or late phases (E), resulting from retinal pigment epithelium (RPE) window defects, without any other abnormalities. Indocyanine green angiography provided a more accurate anatomical evaluation of extent of maculopathy, which remained hypocyanescent centrally, bordered by a ring of small areas of stippled hypercyanescence during intermediate (F) and late phases (G). Third row:OCT (Spectralis, Haag-Streit AG, Koniz, Switzerland) imaging of macula revealed a complete loss of external layers of retina with irregular stippled thickening of RPE (H). Bottom rows (J-M):Progression of maculopathy despite cessation of ritonavir. Each row depicts overall retinal situation at one point in time (J = initial, K = 1 month, L = 3 months, and M = 12 months after cessation of ritonavir). Left column represents global macular thickness (blue color represents thinning of retina), middle column shows results of pseudo-infrared photography, and right column exhibits results of autofluorescence. A progressive increase in both extent of maculopathy and an increase in retinal thinning is obvious.
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F1
Fundus examination revealed discrete macular atrophy of granular appearance with areas of hypo- and hyperpigmentation (Figure 1A). Pseudo-infrared and autofluorescent imaging revealed a more extensive maculopathy than what appeared on fundus examination (Figures 1B,C). Fluorescein angiography disclosed a small area of mottled hyperfluoresence of the left macula due to retinal pigment epithelium (RPE) window defect, without any other abnormalities (Figures 1D,E). Indocyanine green angiography disclosed a larger macular area of hypocyanescence, remaining hypocyanescent in the late phase (Figures 1F,G). Macular optical coherence tomography (OCT) revealed complete loss of the external layers of the retina, irregular stippled thickening of the RPE, and intact inner retina from the inner nuclear layer to the inner limiting membrane (Figure 1H). Despite the cessation of ritonavir, the extent of the maculopathy continued to worsen over the next 18 months (Figures 1J-M).
PMC8249001_02
Multimodal imaging of didanosine peripheral retinopathy (patient 2). Top row:Results of computerized static perimetry (Octopus 300, program G1, Haag-Streit AG, Koniz, Switzerland) 5 years earlier (A) and at time of examination (B) revealed progressive peripheral constriction of visual field in both eyes. Second row:Widefield fundus photography (Optos, GmbH, Zweigneiderlassung Zug, Switzerland) showed a 360  of mid-peripheral areas of chorioretinal atrophy, sometimes coalescent, as well as pigment accumulation mainly in superior retina of both eyes (C,D). Third row:Widefield autofluorescent photography (Optos, GmbH, Zweigneiderlassung Zug, Switzerland) better delineated shape and size of numerous mid-peripheral nummular areas of hypofluorescence in both eyes (E,F). Fourth row:Posterior pole autofluorescence imaging (Spectralis, Haag-Streit AG, Koniz, Switzerland) revealed a normal macular area, peripapillary hypofluorescence, and a 360  perimacular ring of finely stippled hyperautofluorescence posterior to roundish areas of hypofluorescence (G,H). Bottom row:OCT measurements (Spectralis, Haag-Streit AG, Koniz, Switzerland) of right eye (I,J) and left eye (K,L) revealed normal thicknesses for both RNFL (I,K) and retinal ganglion cell layer (RGCL) (J,L).
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F2
The patient complained of slowly progressive peripheral visual loss for the past 5 years (Figure 2A). The VF was severely constricted OU (Figure 2B). Fundus examination revealed mid-peripheral roundish and well-delineated areas of chorioretinal atrophy, surrounded by hyperpigmentation, sparing the posterior pole (Figures 2C,D). Wide-field autofluorescent photography better delineated the peripheral punched-out round zones of chorioretinal atrophy (Figures 2E,F). Autofluorescence of the macula was normal but revealed a perimacular ring of fine hyperautofluorescent stippling (Figures 2G,H). Macular OCT and OCT angiography were unremarkable in both eyes (not shown), as were retinal nerve fiber layer and retinal ganglion cell layer thicknesses (Figures 2I-L).