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

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

doi:10.1016/j.ajo.2024.02.005

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

Am J Ophthalmol. 2024 Feb 15:263:1-10. doi: 10.1016/j.ajo.2024.02.005. Online ahead of print.

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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: michel.michaelides@ucl.ac.uk.

PMID: 38364953
DOI: 10.1016/j.ajo.2024.02.005

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 mm² at baseline and mean of 6.13 ± 3.62 mm² 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.