Genetics, Clinical Characteristics, and Natural History of PDE6B-Associated Retinal Dystrophy.

Yu Fujinami-Yokokawa, Kaoru Fujinami, Michalis Georgiou, Omar A Mahroo, Malena Daich Varela, Michel Michaelides, Andrew R Webster, Shaima Awadh Hashem, Yannik Laich, Thales A C de Guimaraes, Naser Ali

Journal: American journal of ophthalmology 2024;263():1-10

PMID: 38364953

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Abstract

PURPOSE

To analyze the clinical characteristics, natural history, and genetics of PDE6B-associated retinal dystrophy.

DESIGN

Retrospective, observational cohort study.

METHODS

Review of medical records and retinal imaging, including fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT) of patients with molecularly confirmed PDE6B-associated retinal dystrophy in a single tertiary referral center. Genetic results were reviewed, and the detected variants were assessed.

RESULTS

Forty patients (80 eyes) were identified and evaluated longitudinally. The mean age (±SD, range) was 42.1 years (± 19.0, 10-86) at baseline, with a mean follow-up time of 5.2 years. Twenty-nine (72.5%) and 27 (67.5%) patients had no or mild visual acuity impairment at baseline and last visit, respectively. Best-corrected visual acuity (BCVA) was 0.56 ± 0.72 LogMAR (range -0.12 to 2.80) at baseline and 0.63 ± 0.73 LogMAR (range 0.0-2.80) at the last visit. BCVA was symmetrical in 87.5% of patients. A hyperautofluorescent ring was observed on FAF in 48 and 46 eyes at baseline and follow-up visit, respectively, with a mean area of 7.11 ± 4.13 mm at baseline and mean of 6.13 ± 3.62 mm at the follow-up visit. Mean horizontal ellipsoid zone width at baseline was 1946.1 ± 917.2 µm, which decreased to 1763.9 ± 827.9 µm at follow-up. Forty-four eyes had cystoid macular edema at baseline (55%), and 41 eyes (51.3%) at follow-up. There were statistically significant changes during the follow-up period in terms of BCVA and the ellipsoid zone width. Genetic analysis identified 43 variants in the PDE6B gene, including 16 novel variants.

CONCLUSIONS

This study details the natural history of PDE6B-retinopathy in the largest cohort to date. Most patients had mild to no BCVA loss, with slowly progressive disease, based on FAF and OCT metrics. There is a high degree of disease symmetry and a wide window for intervention.

Address: From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom.; From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; Jones Eye Institute, University of Arkansas for Medical Sciences (M.G.), Little Rock, Arkansas, USA.; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research (Y.F.Y.), National Institute of Sensory Organs, NHONHO Tokyo Medical Center, Tokyo, Japan; Department of Health Policy and Management (Y.F.Y.), Keio University School of Medicine, Tokyo, Japan.; From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; Eye Center, Faculty of Medicine, University Freiburg (Y.L.), Germany.; From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom.; From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; Section of Ophthalmology, King's College London, St Thomas' Hospital Campus (O.A.M.), London, United Kingdom; Department of Physiology, Development and Neuroscience, University of Cambridge (O.A.M.), Cambridge, United Kingdom.; From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; Laboratory of Visual Physiology, Division of Vision Research (Y.F.Y.), National Institute of Sensory Organs, NHONHO Tokyo Medical Center, Tokyo, Japan.; From the Moorfields Eye Hospital (S.A.H., M.G., Y.L., M.D.V., T.A.C.d.G., N.A., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom; UCL Institute of Ophthalmology, University College London (S.A.H., M.G., Y.F.Y., Y.L., M.D.V., T.A.C.d.G., O.A.M., A.R.W., K.F., M.M.), London, United Kingdom. Electronic address: [email protected].

DOI: 10.1016/j.ajo.2024.02.005

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MeSH Terms: Humans, Retrospective Studies, Cyclic Nucleotide Phosphodiesterases, Type 6, Male, Female, Visual Acuity, Adult, Middle Aged, Tomography, Optical Coherence, Adolescent, Aged, Young Adult, Child, Retinal Dystrophies, Fluorescein Angiography, Aged, 80 and over, Follow-Up Studies, Mutation, Electroretinography, DNA Mutational Analysis