Inherited Retinal Disease

Study looks at natural history of IRDs with gene mutations

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Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene have unique characteristics which may help identify potential endpoints for therapeutic studies.

In this international, multicenter, retrospective cohort study, the medical records of 82 patients with GUCY2D-associated LCA (autosomal recessive; n = 14) or CORD (autosomal dominant; n = 68) were reviewed. There were median follow-up times of 5.2 years and 7.2 years for LCA and CORD, respectively.

The following were key takeaways from the LCA cohort:
-LCA often presented during the first year of life
-Best-corrected visual acuity (BCVA) ranged from no light perception to 1.00 logMAR
-BCVA remained relatively stable during follow-up
-Imaging showed little to no structural degeneration

The following were key takeaways from the CORD cohort:
-Progressive vision loss generally started in the second decade of life
– BCVA declined yearly by 0.022 logMAR with no difference between GUCY2D variants
– the probability of being blind/severely visually impaired was 32% at age 40.
-BCVA significantly correlated with integrity of the ellipsoid zone and that of the external limiting membrane on spectral-domain OCT

“The integrity of the [external limiting membrane] and [ellipsoid zone] may be suitable structural endpoints for therapeutic studies of GUCY2D-associated CORD,” the authors wrote.

Hahn LC, Georgiou M, Almushattat H, et al. The Natural History of Leber Congenital Amaurosis and Cone-Rod Dystrophy Associated with Variants in the GUCY2D Gene. Ophthalmol Retina. 2022;S2468-6530(22)00107-5. doi: 10.1016/j.oret.2022.03.008. Epub ahead of print. PMID: 35314386.