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Novel clinical findings in autosomal recessive NR2E3-related retinal dystrophy
摘要： Purpose To evaluate the clinical phenotype of autosomal recessive NR2E3-related retinal dystrophy. Methods We retrospectively studied 11 patients carrying out at least 2 NR2E3 mutations; they had undergone comprehensive ophthalmological examination, fundus photography, optical coherence tomography, electrophysiological testing, and visual field at the Regional Reference Center for Hereditary Retinal Degenerations of the Eye Clinic in Florence. Results Five females and six males with a diagnosis of NR2E3-related retinal dystrophy were included in the study. All patients complained of nyctalopia. Visual acuity ranged from 0.00 logMAR to hand motion. Two patients presented bull’s eye maculopathy, and one of these was characterized by a triple hyper-autofluorescent ring at the fundus autofluorescence examination. Three patients showed small yellowish dots and spots at the mid-periphery. One patient was characterized by widespread subretinal drusenoid deposits (SDD) at the posterior pole. Four patients showed vitreous abnormalities. Optical coherence tomography (OCT) examinations detected variable degrees of abnormal retinal lamination and schitic changes. Seven patients were compound heterozygous and four were homozygous for mutations in NR2E3. Conclusions Our study confirmed high variable phenotype in autosomal recessive NR2E3-related retinal dystrophy. Bull’s eye maculopathy, subretinal drusenoid deposits, and foveal hypoplasia represent novel clinical findings in NR2E3-related retinal dystrophy. Macular involvement was detectable in all the patients, and the abnormal foveal avascular zone (FAZ) supports the role of NR2E3 in retinal development.
关键词： Retinal dystrophy,Foveal hypoplasia,Retinitis pigmentosa,Subretinal drusenoid deposits,Autosomal recessive disease,Goldmann-Favre,NR2E3
更新于2025-09-23 15:23:52
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Contrast sensitivity deficits in patients with mutation-proven inherited retinal degenerations
摘要： Background: Patients with retinal diseases frequently complain of poor visual function even when visual acuity is relatively unaffected. This clinical finding has been attributed to deficits in contrast sensitivity (CS). The purpose of our study was to evaluate the CS in patients with clinical and genetic diagnosis of inherited retinal degeneration (IRD) and relatively preserved visual acuity. Methods: Seventeen patients (30 eyes) with IRD and visual acuity of 20/40 or better, and 18 controls (18 eyes) without any ocular condition underwent slit lamp examination, visual acuity testing via standard Snellen chart testing, CS testing via the Quick Contrast Sensitivity Function (QCSF), and Spectral Domain Optical Coherence Tomography (SD-OCT). CS were measured at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). T tests with general estimated equations were used to compare CS between groups. Wald chi square followed by pairwise comparisons was used to compare CS between multiple groups. Results: We included 12 patients with rod-cone dystrophy (RCD), 3 patients with Stargardt disease (STGD) and 2 patients with Best disease. Patients with IRD had significantly worse CS than controls (p < 0.001) in all spatial frequencies. Patients with STGD had more marked deficits in CS than patients with Best disease (p < 0.001) and RCD (p < 0.001) despite having similar visual acuities. Conclusion: Patients with IRD, especially patients with STGD with relatively preserved visual acuity have marked deficits in CS when measured across a range of spatial frequencies. We recommend that clinical trials for STGD incorporate CS measured over a range of spatial frequencies as a secondary clinical endpoint for monitoring visual function. CS may provide an explanation for complaints of visual dysfunction when visual acuity is not significantly altered.
关键词： Best disease,Contrast sensitivity,Retinal dystrophy,Retinitis Pigmentosa,Stargardt disease
更新于2025-09-23 15:23:52
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Determination of Rod and Cone Influence to the Early and Late Dynamic of the Pupillary Light Response
摘要： PURPOSE. This study aims to identify which aspects of the pupil light re?ex are most in?uenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor de?ciency. METHODS. One-month-old wild type (WT), rodless (Rho(cid:2)/(cid:2)), coneless (Cnga3(cid:2)/(cid:2)), or photoreceptor less (Cnga3(cid:2)/(cid:2); Rho(cid:2)/(cid:2) or Gnat1(cid:2)/(cid:2)) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the ?rst 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude. RESULTS. Rho(cid:2)/(cid:2) mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3(cid:2)/(cid:2) mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3(cid:2)/(cid:2) mice demonstrated marked prolongation of the pupillary constriction. Cnga3(cid:2)/(cid:2); Rho(cid:2)/(cid:2) mice had no pupil response to red light of low and medium intensity. CONCLUSIONS. From speci?c gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models.
关键词： pupillary response,photoreceptors,mouse model,retinal dystrophy
更新于2025-09-11 14:15:04
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Multimodal imaging in a pedigree of X-linked Retinoschisis with a novel RS1 variant
摘要： To describe the clinical phenotype and genetic cause underlying the disease pathology in a pedigree (affected n = 9) with X-linked retinoschisis (XLRS1) due to a novel RS1 mutation and to assess suitability for novel therapies using multimodal imaging.
关键词： X-linked Retinoschisis,Inherited maculopathy,Inherited retinal dystrophy,Retinoschisin
更新于2025-09-10 09:29:36
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Autosomal Dominant Retinal Dystrophies Caused by a Founder Splice Site Mutation, c.828+3A>T, in <i>PRPH2</i> and Protein Haplotypes in <i>trans</i> as Modifiers
摘要： PURPOSE. We determined the phenotypic variation, disease progression, and potential modi?ers of autosomal dominant retinal dystrophies caused by a splice site founder mutation, c.828t3A>T, in the PRPH2 gene. METHODS. A total of 62 individuals (19 families) harboring the PRPH2 c.828t3A>T mutation, had phenotype analysis by fundus appearance, electrophysiology, and visual ?elds. The PRPH2 haplotypes in trans were sequenced for potential modifying variants and generalized estimating equations (GEE) used for statistical analysis. RESULTS. Several distinct phenotypes caused by the PRPH2 c.828t3A>T mutation were observed and fell into two clinical categories: Group I (N ? 44) with mild pattern dystrophies (PD) and Group II (N ? 18) with more severe cone-rod dystrophy (CRD), retinitis pigmentosa (RP), and central areolar chorioretinal dystrophy (CACD). The PRPH2 Gln304-Lys310-Asp338 protein haplotype in trans was found in Group I only (29.6% vs. 0%), whereas the Glu304-Lys310-Gly338 haplotype was predominant in Group II (94.4% vs. 70.4%). Generalized estimating equations analysis for PD versus the CRD/CACD/RP phenotypes in individuals over 43 years alone with the PRPH2 haplotypes in trans and age as predictors, adjusted for correlation within families, con?rmed a signi?cant effect of haplotype on severity (P ? 0.03) with an estimated odds ratio of 7.16 (95% con?dence interval [CI] ? [2.8, 18.4]). CONCLUSIONS. The PRPH2 c.828t3A>T mutation results in multiple distinct phenotypes likely modi?ed by protein haplotypes in trans; the odds of having the CACD/RP-like phenotype (versus the PD phenotype) are 7.16 times greater with a Glu304-Lys310-Gly338 haplotype in trans. Further functional studies of the modifying haplotypes in trans and PRPH2 splice variants may offer therapeutic targets.
关键词： retinal dystrophy,phenotype,genetic modi?ers
更新于2025-09-09 09:28:46
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Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up
摘要： To longitudinally characterize structural retinal changes in achromatopsia (ACHM) over extended follow-up. Fifty molecularly confirmed ACHM subjects underwent serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Foveal structure on SD-OCT was graded and compared for evidence of progression, and foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness were serially measured. FAF patterns were characterized and compared over time. Mean SD-OCT follow-up was 61.6 months (age range at baseline, 6–52 years). Forty-five of the subjects had serial FAF (mean follow-up: 48.5 months). Only 6 (12%) of the subjects demonstrated qualitative change on serial foveal SD-OCT scans. Among the entire cohort, there was no statistically significant change over time in FTRT (P ? 0.2459) or hyporeflective zone (HRZ) diameter (P ? 0.3737). There was a small—but statistically significant—increase in ONL thickness (P ? 0.0084). Three different FAF patterns were observed: centrally increased FAF (13/45), normal FAF (14/45), and well-demarcated reduced FAF (18/45), with the latter group displaying a small gradual increase in the area of reduced FAF of 0.055 mm2 over 43.4 months (P ? 0.0011). This longitudinal study of retinal structure in ACHM represents the largest cohort and longest follow-up period to date. Our findings support the presiding notion that ACHM is essentially a stationary condition regarding retinal structure, and any change over time is likely to be small, slow, and variable across patients. This may potentially afford a wider window for therapeutic intervention.
关键词： gene therapy,achromatopsia,retinal dystrophy,optical coherence tomography
更新于2025-09-09 09:28:46