RESUMO
PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMO
PURPOSE: 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. DESIGN: Retrospective single-center cohort study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.