This study describes the clinical, genetic, and histopathological features in patients with
-associated retinal dystrophies. Nine male patients from eight unrelated families underwent a comprehensive ...ophthalmic examination. Additionally, the histopathology of the right eye from a patient with an end-stage cone-rod-dystrophy (CRD)/sector retinitis pigmentosa (RP) phenotype was examined. All
mutations causing a CRD phenotype were situated in exon ORF15. The mean best-corrected visual acuity (BCVA, decimals) was 0.58 (standard deviation (SD)): 0.34; range: 0.05-1.13); and the mean spherical refractive error was -4.1 D (SD: 2.11; range: -1.38 to -8.19). Hyperautofluorescent rings were observed in six patients. Full-field electroretinography responses were absent in all patients. The visual field defects ranged from peripheral constriction to central islands. The mean macular sensitivity on microperimetry was 11.6 dB (SD: 7.8; range: 1.6-24.4) and correlated significantly with BCVA (
= 0.907;
= 0.001). A histological examination of the donor eye showed disruption of retinal topology and stratification, with a more severe loss found in the peripheral regions. Reactive gliosis was seen in the inner layers of all regions. Our study demonstrates the highly variable phenotype found in
-associated retinal dystrophies. Therapies should be applied at the earliest signs of photoreceptor degeneration, prior to the remodeling of the inner retina.
Purpose
To investigate the impact of the OrCam MyEye 2.0 (OrCam) on the quality of life and rehabilitation needs in patients with advanced retinitis pigmentosa (RP) or cone‐rod dystrophies (CRD). The ...OrCam is a wearable low‐vision aid that converts visual information to auditive feedback (e.g. text‐to‐speech, barcode and facial recognition).
Methods
Patients with a clinical diagnosis of RP (n = 9, 45%) or CRD (n = 11; 55%), and a best‐corrected visual acuity of ≤20/400 Snellen were invited to participate in this study. Questionnaires were administered at baseline and after 5.2 (standard deviation ± 1.5) weeks, which included the Dutch version of the National Eye Institute Visual Functioning Questionnaire (NEI‐VFQ), the Participation and Activity Inventory (PAI) and the OrCam Function Questionnaire (OFQ).
Results
Following OrCam testing, significant improvements were observed in the ‘near activities’ subscale of the NEI‐VFQ (p < 0.001); the ‘visual functioning’ subscale of the re‐engineered NEI‐VFQ (p = 0.001); the ‘reading’ rehabilitation goal of the PAI (p = 0.005) and the overall score of the OFQ (p < 0.001). The observed changes in questionnaire scores did not differ between phenotypes. Advantages and limitations of the OrCam were reported by patients. Three patients (15%) continued rehabilitation with the OrCam after completion of this study.
Conclusions
The OrCam mainly improves reading domains in patients with advanced stages of RP or CRD. Further improvements in the OrCam are needed to address current limitations, which may enhance its utility for patients with RP or CRD.
Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies characterized by the degeneration of rod photoreceptors, followed by the degeneration of cone photoreceptors. As a result ...of photoreceptor degeneration, affected individuals experience gradual loss of visual function, with primary symptoms of progressive nyctalopia, constricted visual fields and, ultimately, central vision loss. The onset, severity and clinical course of RP shows great variability and unpredictability, with most patients already experiencing some degree of visual disability in childhood. While RP is currently untreatable for the majority of patients, significant efforts have been made in the development of genetic therapies, which offer new hope for treatment for patients affected by inherited retinal dystrophies. In this exciting era of emerging gene therapies, it remains imperative to continue supporting patients with RP using all available options to manage their condition. Patients with RP experience a wide variety of physical, mental and social-emotional difficulties during their lifetime, of which some require timely intervention. This review aims to familiarize readers with clinical management options that are currently available for patients with RP.
Purpose
To assess the longitudinal vision‐related quality of life among patients with CRB1‐associated inherited retinal dystrophies.
Methods
In this longitudinal questionnaire study, the National Eye ...Institute Visual Function Questionnaire (39 items, NEI VFQ‐39) was applied at baseline, two‐year follow‐up, and 4‐year follow‐up in patients with pathogenic CRB1 variants. Correction added on 20 November 2023, after first online publication: The preceding sentence has been updated in this version. Classical test theory was performed to obtain subdomain scores and in particular ‘near activities’ and ‘total composite’ scores. The Rasch analysis based on previous calibrations of the NEI VFQ‐25 was applied to create visual functioning and socio‐emotional subscales.
Results
In total, 22 patients with a CRB1‐associated retinal dystrophy were included, … with a median age of 25.0 years (interquartile range: 13–31 years) at baseline and mean follow‐up of 4.0 ± 0.3 years. Correction added on 20 November 2023, after first online publication: The preceding sentence has been updated in this version. A significant decline at 4 years was observed for ‘near activities’ (51.0 ± 23.8 vs 35.4 ± 14.7, p = 0.004) and ‘total composite’ (63.0 ± 13.1 vs 52.0 ± 12.1, p = 0.001) subdomain scores. For the Rasch‐scaled scores, the ‘visual functioning’ scale significantly decreased after 2 years (−0.89 logits; p = 0.012), but not at 4‐year follow‐up (+0.01 logits; p = 0.975). Correction added on 20 November 2023, after first online publication: In the preceding sentence, “…after 4 years…” has been corrected to “…after 2 years…” in this version. The ‘socio‐emotional’ scale also showed a significant decline after 2 years (−0.78 logits, p = 0.033) and 4 years (−0.83 logits, p = 0.021).
Conclusion
In the absence of an intervention, a decline in vision‐related quality of life is present in patients with pathogenic CRB1 variants at 4‐year follow‐up. Patient‐reported outcome measures should be included in future clinical trials, as they can be a potential indicator of disease progression and treatment efficacy.
To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP).
Retrospective, noncomparative clinical study.
Preoperative, intraoperative, and postoperative data of ...patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe.
In total, 295 eyes of 226 patients were included in the study. The mean age at surgery of the first eye was 56.1 ± 17.9 years. Following surgery, best-corrected visual acuity (BCVA) improved significantly from 1.03 to 0.81 logMAR (ie, 20/214 to 20/129 Snellen) in the first treated eye (−0.22 logMAR; 95% CI = −0.31 to −0.13; P < .001) and from 0.80 to 0.56 logMAR (ie, 20/126 to 20/73 Snellen) in the second treated eye (−0.24 logMAR; 95% CI = −0.32 to −0.15; P < .001). Marked BCVA improvements (postoperative change in BCVA of ≥0.3 logMAR) were observed in 87 of 226 patients (39%). Greater odds for marked visual improvements were observed in patients with moderate visual impairment or worse. The most common complications were zonular dialysis (n = 15; 5%) and (exacerbation of) cystoid macular edema (n = 14; 5%), respectively. Postoperative posterior capsular opacifications were present in 111 of 295 eyes (38%).
Significant improvements in BCVA are observed in most patients with RP following cataract surgery. Baseline BCVA is a predictor of visual outcome. Preoperative evaluation should include the assessment of potential zonular insufficiency and the presence of CME, as they are relatively common and may increase the risk of complications.
To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults.
This was a multicenter international clinical cohort study.
Review ...of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects.
In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades.
In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.
•The current study established the largest and most characterized cohort of molecularly confirmed patients with KCNV2-associated retinopathy.•Report 1 highlights the genetic background, evidence of electroretinography stability over a broad age range, and the severe phenotype of the disease.
To investigate the natural history of RHO-associated retinitis pigmentosa (RP).
A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP.
Based on visual fields, ...time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20°) and blindness (central visual field <10°), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 ≤ BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's ρ = 0.733; P < 0.001).
Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies.
This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the
gene. A ...total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation SD ± 11.0; range from 17.5 to 53.9) at the most recent examination. The presence and onset of neurological, audiological and ophthalmic symptoms were variable, with no evident order of symptom appearance. The mean best-corrected visual acuity was 1.1 logMAR (SD ± 0.9; range from 0.1 to 2.8; equivalent to 20/250 Snellen) and showed a trend of progressive decline. Different types of cataract were observed in 13 out of 15 patients (87%), which also included congenital forms of cataract. Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%). From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity. Given the variable nature of PHARC, an early multidisciplinary assessment is recommended to assess disease severity.
PurposeEye inflammation may occur in patients with inherited retinal dystrophies (IRDs) and is seen frequently in IRDs associated with mutations in the CRB1 gene. The purpose of this study was to ...determine the types of inflammatory cells involved in IRDs, by deep profiling the composition of peripheral blood mononuclear cells of patients with a CRB1-associated IRD.MethodsThis study included 33 patients with an IRD with confirmed CRB1 mutations and 32 healthy controls. A 43-parameter flow cytometry analysis was performed on peripheral blood mononuclear cells isolated from venous blood. FlowSOM and manual Boolean combination gating were used to identify and quantify immune cell subsets.ResultsComparing patients with controls revealed a significant increase in patients in the abundance of circulating CD4+ T cells and CD8+ T cells that express sialyl Lewis X antigen. Furthermore, we detected a decrease in plasmacytoid dendritic cells and an IgA+CD24+CD38+ transitional B-cell subset in patients with an IRD.ConclusionsPatients with a CRB1-associated IRD show marked changes in blood leukocyte composition, affecting lymphocyte and dendritic cell populations. These results implicate inflammatory pathways in the disease manifestations of IRDs.
To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials.
...Single-center, prospective case series.
An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging.
Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 86%), cone-rod dystrophy (2 9%), or isolated macular dystrophy (1 5%). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up.
In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.
•Visual acuity, visual fields, and full-field stimulus threshold remain relatively stable over 2 years.•Macular sensitivity on microperimetry was significantly reduced at the 2-year follow-up.•Microperimetry should be considered as an end point in future clinical trials.
PDF
