Abstract
Purpose :
Neural retina leucine zipper (NRL)-associated retinopathies are rare forms of retinal dystrophy that can be inherited in autosomal dominant (AD) or autosomal recessive (AR) manner, each with a unique phenotype. The purpose of this study is to describe ophthalmic findings along with neuroimaging in patients with NRL-associated retinopathy.
Methods :
10 eyes of 5 related patients aged 3.2-36.2y with the NRL p.Pro51Ser pathogenic variant were included in this study. Best-corrected visual acuity (BCVA), refractive error (Rx), intraocular pressure (IOP), and axial length (AL) measurements were reviewed. Ultra-widefield color and autofluorescence fundus imaging and optical coherence tomography (OCT) imaging were analyzed; metrics compared using Pearson correlation and paired t-tests.
Results :
Mean BCVA was measured at 20/39 (20/25-20/63) in the setting of mean spherical equivalent of +2.04 D (-0.50 D to +6.13 D) and mean axial length of 20.42 mm (19.37-21.10 mm). Narrow angles were identified in both adult patients leading to laser peripheral iridotomy. A macular hyperautofluorescent ring was detected in all patients and correlated with their respective retained ellipsoid zone (EZ) on OCT (Pearson r= 0.95, 0.98, p=0.01, 0.004 for outer and inner edge of ring, respectively). The horizontal diameter of the hyperautofluorescent ring aligned with maintained EZ (Paired t-test, t=-0.41, p=0.70). All patients had anomalous appearing nerves and elevated average retinal nerve fiber layer thickness with a mean of 162.70 um (126-238 um). One patient was noted to have elevated opening pressure (30.6cm H2O) on lumbar puncture with subsequent improvement after trial of acetazolamide.
Conclusions :
NRL encodes a basic-motif leucine zipper protein expressed in the retinal photoreceptors and is essential for rod photoreceptor development. There is some evidence of expression of NRL or a similar protein in developing brain. However, NRL’s potential expression and role beyond the retina remains poorly understood. Our patients have an AD inheritance pattern; nonetheless, certain features are more typically associated with AR NRL-associated retinopathy. Novel findings described include elevated optic nerves, narrow anatomical angles, and short AL. Further research is needed to understand NRL’s role in brain and retinal development to elucidate how distinct NRL mutations lead to specific phenotypes.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.