Late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration
To report the clinical and genetic characteristics of 6 cases with late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration.
Clinical and genetic data were collected from 6 independent patients who complained of night blindness in their fifth to eighth decade of life. The ophthalmological examinations included ophthalmoscopy, fundus autofluorescence (FAF), and full-field electroretinography (ERG). Whole exome sequencing with target gene analysis was performed to determine the causative genes and variants.
All of the patients first complained of night blindness at the ages of 40–71 years. Funduscopic examinations demonstrated white or atrophic flecks scattered in the posterior pole and peripheral retina bilaterally. FAF showed patchy hypo-autofluorescence spots in the posterior pole similar to that of the trickling type of age-related macular degeneration (AMD). The region of abnormal FAF rapidly expanded with age, and one eye developed a choroidal neovascularization. The full-field scotopic ERGs with 20 min of dark adaptation were severely reduced or extinguished in all cases. There was partial recovery of the ERGs after 180 min of dark adaptation. The cone ERGs were reduced in all cases. Whole exome sequencing revealed no pathogenic variants of 301 retinal disease-associated genes.
The six cases had some common features with the flecked retina syndrome, familial drusen, and late-onset retinal degeneration although none had pathogenic variants causative for these disorders. These cases may represent a subset of severe trickling AMD or a new clinical entity of acquired pan-retinal visual cycle deficiency of unknown etiology.
KeywordsNight blindness White dot syndrome Macular degeneration Trickling AMD
We thank the patients and their families for participation in this study. We thank Professor Emeritus Duco Hamasaki of the Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL, for discussions and editing our manuscript.
This study is supported by research grants from the Japan Agency for Medical Research and Development (AMED), the Ministry of Health, Labor and Welfare, and Japan (18ek0109282h0002 to TI), Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science (H26-26462674 to KT, 16H06269, 16KK0193 to KF), National Hospital Organization Network Research Fund (H30-NHO-Sensory Organs-03 to KF, KT), and Novartis Research Grant (2018 to KT). Kaoru Fujinami is supported by Foundation Fighting Blindness, USA, and Great Britain Sasakawa Foundation Butterfield Awards, UK.
Compliance with ethical standards
Conflict of interest
The authors have no proprietary or commercial interest in any materials discussed in this article.
Statement of human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Review Board/Ethics Committee of the National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Reference: R18-029) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Statement on the welfare of animals
This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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