To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). Retrospective cohort study. Seventy-eight patients (156 eyes) affected by EMAP. We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Best Vitelliform Macular Dystrophy (BVMD) is a dominantly inherited retinal disease caused by dominant variants in the BEST1 gene. The original classification of BVMD is based on biomicroscopy and color fundus photography (CFP); however, advancements in retinal imaging provided unique structural, vascular, and functional data and novel insights on disease pathogenesis. Quantitative fundus autofluorescence studies informed us that lipofuscin accumulation, the hallmark of BVMD, is unlikely to be a primary effect of the genetic defect. It could be due to a lack of apposition between photoreceptors and retinal pigment epithelium in the macula with subsequent accumulation of shed outer segments over time. Optical Coherence Tomography (OCT) and adaptive optics imaging revealed that vitelliform lesions are characterized by progressive changes in the cone mosaic corresponding to a thinning of the outer nuclear layer and then disruption of the ellipsoid zone, which are associated with a decreased sensitivity and visual acuity. Therefore, an OCT staging system based on lesion composition, thus reflecting disease evolution, has been recently developed. Lastly, the emerging role of OCT Angiography proved a greater prevalence of macular neovascularization, the majority of which are non-exudative and develop in late disease stages. In conclusion, effective diagnosis, staging, and clinical management of BVMD will likely require a deep understanding of the multimodal imaging features of this disease.

To identify the vascular biomarkers of peripheral capillary nonperfusion in patients affected by naive central retinal vein occlusion (CRVO), and to analyze their changes over the follow-up. Consecutive prospective case series with a planned follow-up of 2 years. Thirty-five patients affected by CRVO and 35 healthy gender- and age-matched subjects were enrolled in the study. Ophthalmic examination included best corrected visual acuity (BCVA), ultrawidefield fluorescein angiography (UWFFA), OCT, and OCT angiography (OCTA). Vessel density (VD) at the superficial capillary plexus and deep capillary plexus (DCP) were calculated on OCTA images. The ischemic index (ISI) was calculated on UWFFA. The mean baseline ISI was 37%, increasing to 40% at the end of the follow-up, whereas it was 4.9% in the patients' fellow eyes and 4.5% in the control group with no change over the follow-up. OCT angiography revealed VD reduction in the DCP, considering both 3 × 3 mm and 12 × 12 mm scans. The correlation analyses revealed that DCP VD was the only parameter showing a statistically significant correlation with the foveal avascular zone (FAZ) area, BCVA, and ISI. Deep capillary plexus VD impairment is detectable in all CRVO cases, variably involving both the central retina (with enlarged FAZ) and the periphery (with VD reduction in the peripheral retina). The severity of DCP VD reduction has correlates with various clinical markers. Deep capillary plexus VD may represent a crucial biomarker to characterize CRVO, and further studies are necessary to identify the cutoff thresholds for the different clinical manifestations.

Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian decent with only few reports of North African descent. Genome, targeted next-generation and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium (RPE) cells and zebrafish. Variants' pathogenicity was accessed using 3D-modeling and/or ROs. Here we identified a novel gene defect with three distinct pathogenic variants in UBAP1L in four independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the RPE and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin associated (SOUBA) domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the SOUBA domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein. Biallelic UBAP1L variants are a novel cause of IRDs, most likely enriched in the North African population.

To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations. Retrospective single-center cohort study. Twenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing. The median (interquartile ranges) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy (MA) was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm³ (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm³/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference between the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of MA. Progressive MA in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with MA. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.