Visual Acuity by Decade in 139 Males with RPGR-Associated Retinitis Pigmentosa.
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ABSTRACT:
SUBMITTER: De Silva SR
PROVIDER: S-EPMC10587616 | biostudies-literature | 2024 Mar-Apr
REPOSITORIES: biostudies-literature
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Visual Acuity by Decade in 139 Males with <i>RPGR</i>-Associated Retinitis Pigmentosa.
De Silva Samantha R SR Chan Hwei Wuen HW Agarwal Aditi A Webster Andrew R AR Michaelides Michel M Mahroo Omar A OA
Ophthalmology science 20230724 2
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Project description:IntroductionChoroideremia and RPGR-associated retinitis pigmentosa (RP) are two distinct inherited rod-cone degenerations, where good visual acuity (VA) is maintained until late disease stages, limiting its usefulness as a disease marker. Low luminance VA and low luminance deficit (standard VA minus low luminance VA) may be more sensitive visual function measures.MethodsStandard VA was obtained using Early Treatment Diabetic Retinopathy Study letter charts (Precision Vision, Bloomington, IL, USA). Low luminance VA was assessed using a 2.0-log unit neutral density filter, with the same chart setup, without formal dark adaptation. Mean central retinal sensitivity was assessed using MAIA microperimetry (Centervue SpA, Padova, Italy). Optical coherence tomography imaging was attained with Heidelberg Eye Explorer software (Heidelberg Engineering, Heidelberg, Germany).ResultsTwenty-four male participants with confirmed pathogenic RPGR mutations, 44 male participants with confirmed pathogenic CHM mutations, and 62 age-matched controls underwent clinical assessment prior to clinical trial recruitment. Low luminance VA was significantly reduced in both disease groups compared to controls. The low luminance deficit correlated with microperimetry retinal sensitivity and ellipsoid zone width. Eleven participants with moderate VA had poor low luminance VA (subsequently a large low luminance deficit), no detectable microperimetry sensitivity, and severely constricted ellipsoid zone widths.ConclusionsLow luminance VA and subsequently low luminance deficit are useful markers of central macular visual function in both choroideremia and RPGR-associated RP, when standard VA is preserved.Translational relevanceLow luminance visual acuity and low luminance deficit are useful vision measures in two distinct rod-cone degenerations and may be useful in other retinal degenerations.
| S-EPMC7900861 | biostudies-literature
Project description:PurposePeripheral visual fields have not been as well defined by static automated perimetry as kinetic perimetry in RPGR-related retinitis pigmentosa. This study explores the pattern and sensitivities of peripheral visual fields, which may provide an important end point when assessing interventional clinical trials.MethodsA retrospective observational cross-sectional study of 10 genetically confirmed RPGR subjects was performed. Visual fields were obtained using the Octopus 900 perimeter. Interocular symmetry and repeatability were quantified. Visual fields were subdivided into central and peripheral subfields for analysis.ResultsMean patient age was 32 years old (20 to 49 years old). Average mean sensitivity was 7 dB (SD = 3.67 dB) and 6.8 dB (SD = 3.4 dB) for the right and left eyes, respectively, demonstrating interocular symmetry. Coefficient of repeatability for overall mean sensitivity: <2 dB. Nine out of 10 subjects had a preserved inferotemporal subfield, whose mean sensitivity was highly correlated to the central field (r2 = 0.78, P = 0.002 and r2 = 0.72, P = 0.002 for the right and left eyes, respectively). Within the central field, sensitivities were greater in the temporal than the nasal half (t-test, P = 0.01 and P = 0.03 for the right and left eyes, respectively).ConclusionsOctopus static-automated perimeter demonstrates good repeatability. Interocular symmetry permits use of the noninterventional eye as an internal control. In this cohort, the inferotemporal and central visual fields are preserved into later disease stages likely mapping to populations of surviving cones.Translational relevanceA consistently preserved inferotemporal island of vision highly correlated to that of the central visual field may have significance as a possible future therapeutic site.
| S-EPMC9123484 | biostudies-literature
Project description:Background/objectivesTo investigate the association between visual acuity (VA) and visual field (VF) and its reproducibility in patients with retinitis pigmentosa (RP).Subjects/methodsThe study cohort comprised 227 eyes of 227 patients with RP. The reproducibility of two Humphrey VF tests (10-2 Swedish Interactive Threshold Algorithm [SITA] tests) performed within a period of 3 months was calculated using the root mean squared error (RMSE) of each VF test point's sensitivity. The association between the logarithm of the minimum angle of resolution (logMAR) VA and VF sensitivity was investigated. Additionally, the relationship between RMSE and age, fixation loss, false positives, false negatives, and logMAR VA was determined.ResultsThe association between visual sensitivity and VA was most tight at the fovea, and it became weak toward the peripheral region in an eccentric manner. VF reproducibility appreciably increased as VA decreased. In particular, reproducibility was significantly decreased when logMAR VA was >0.5 compared with logMAR VA ≤ 0.ConclusionReproducibility of VF tests decreases with a decrease in VA. Careful consideration is necessary when a patient's logMAR VA is >0.5.
| S-EPMC10101998 | biostudies-literature
Project description:PurposeTo evaluate the ability of chromatic pupilloperimetry to identify visual field (VF) defects in patients with retinitis pigmentosa (RP) and to test the correlation between pupilloperimetry impairment and retinal structural and functional measures.MethodsThe pupil responses of 10 patients with RP (mean age, 41.3 ± 16.2 years) and 32 healthy age-similar controls (mean age, 50.7 ± 15.5 years) for 54 focal blue and red stimuli presented in a 24-2 VF were recorded. The pupilloperimetry measures were correlated with Humphrey VF mean deviation, best-corrected visual acuity, and ellipsoid zone area.ResultsSubstantially lower percentage of pupil contraction and maximal pupil contraction velocity (MCV) were recorded in patients with RP throughout the VF in response to blue and red stimuli. The mean absolute deviation (MADEV) in the latency of MCV (LMCV) was significantly larger in patients compared with controls for blue and red stimuli (P = 1.0 × 10-7 and P = 1.0 × 10-6, respectively). The LMCV MADEV differentiated between patients and controls with high specificity and sensitivity (area under the receiver operating characteristic curve, 0.987 and 0.973 for blue and red, respectively). The MADEV of LMCV for blue stimuli correlated with best-corrected visual acuity (ρ = 0.938, P = 5.9 × 10-5) and ellipsoid zone area (ρ = -0.857; P = 0.002). The MADEV of LMCV for red stimuli correlated with Humphrey VF mean deviation (ρ = -0.709; P = 0.022). Minimizing the test to 15 targets maintained a diagnosis of retinal damage in patients with RP with high sensitivity and specificity (area under the receiver operating characteristic curve, 0.927).ConclusionsThe chromatic pupilloperimetry measures significantly correlated with retinal function and structure in patients with RP at various disease stages.Translational relevanceChromatic pupilloperimetry may enable objective assessment of visual field defects and visual acuity in RP.
| S-EPMC7422758 | biostudies-literature
Project description:The X-linked RP3 locus codes for retinitis pigmentosa GTPase regulator (RPGR), a protein of unknown function with sequence homology to the guanine nucleotide exchange factor for Ran GTPase. We created an RPGR-deficient murine model by gene knockout. In the mutant mice, cone photoreceptors exhibit ectopic localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin. Subsequently, both cone and rod photoreceptors degenerate. RPGR was found normally localized to the connecting cilia of rod and cone photoreceptors. These data point to a role for RPGR in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution. The function of RPGR is essential for the long-term maintenance of photoreceptor viability.
| S-EPMC16294 | biostudies-literature
Project description:PurposeTo explore which microperimetry sensitivity index (pointwise sensitivity, mean sensitivity, and volume sensitivity) is suitable as a microperimetry outcome measure in patients with X-linked RPGR-associated retinitis pigmentosa (RP).MethodsMicroperimetry data from patients with RPGR-associated RP were collected and analyzed retrospectively. Fourteen participants completed triplicate microperimetry testing, across 2 consecutive days for the repeatability analyses. Longitudinal data was obtained from 13 participants who completed microperimetry testing at two separate visits.ResultsThe test-retest coefficients of repeatability (CoR) for pointwise sensitivity were ±9.5 dB and ±9.3 dB, in the right and left eyes, respectively. The mean sensitivity CoR for the right and left eyes was ±0.7 dB and ±1.3 dB. Volume sensitivity CoR was ±144.5 dB*deg2 and ±324.2 dB*deg2 for the right and left eyes, respectively. The mean sensitivities were positively skewed toward zero in those with a high number of nonseeing points (arbitrarily assigned to -1.0 dB) and just seen points (0.0 dB). Volume sensitivities were unaffected by the averaging effects of skewed data.ConclusionsClinical trials should report population-specific test-retest variability to determine a clinically significant change. Pointwise sensitivity indices should be used with caution as outcome measures in clinical trials owing to high levels of test-retest variability. Global indices seem to be less prone to variability. Volume sensitivity indices seem to be superior for use in RPGR-associated RP clinical trials compared with mean sensitivity because they are unaffected by the averaging effects of highly skewed data.Translational relevanceCareful selection of sensitivity indices (VA) is required when using microperimetry as a clinical trial outcome measure.
| S-EPMC10259674 | biostudies-literature
Project description:X-linked retinitis pigmentosa (XLRP) is a severe hereditary retinal disorder marked by progressive vision loss due to photoreceptor dysfunction. The retinitis pigmentosa GTPase regulator (RPGR) gene, responsible for most XLRP cases, encodes a protein crucial for the transport of visual signal proteins between the photoreceptor inner and outer segments. However, the mechanism of RPGR mutation causing photoreceptor disorder is not clear and effective treatments remain elusive. This study utilized retinal organoids (ROs) derived from normal and RPGR-mutant human induced pluripotent stem cells (hiPSC) at four developmental stages (40, 90, 150, and 200 days). Single-cell RNA sequencing (scRNA-seq) was conducted on 71,096 cells, including 33,839 cells from the control group and 37,257 cells from the RPGR group. Key retinal cell types were identified and the obtained scRNAseq dataset was validated reliable and high -quality. This study has provided data resources and references for exploring the mechanism of RPGR-related retinal degeneration and support the development of targeted therapies.
| S-EPMC11599861 | biostudies-literature
Project description:Mutations in Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of X-linked Retinitis Pigmentosa (XLRP). The RPGR gene undergoes extensive alternative splicing and encodes for distinct protein isoforms in the retina. Extensive studies using isoform-specific antibodies and mouse mutants have revealed that RPGR predominantly localizes to the transition zone to primary cilia and associates with selected ciliary and microtubule-associated assemblies in photoreceptors. In this chapter, we have summarized recent advances on understanding the role of RPGR in photoreceptor protein trafficking. We also provide new evidence that suggests the existence of discrete RPGR multiprotein complexes in photoreceptors. Piecing together the RPGR-interactome in different subcellular compartments should provide critical insights into the role of alternative RPGR isoforms in associated orphan and syndromic retinal degenerative diseases.
| S-EPMC3464500 | biostudies-literature
Project description:AIM:To gain a better understanding of the overall efficacy of valproic acid (VPA) treatment for retinitis pigmentosa (RP). METHODS:Publications in PubMed, EMBASE, Cochrane Library, Web of Science and Clinicaltrials.gov were searched for clinical trials of patients with RP assigned to treatment with VPA. Patients' pre- and post-treatment visual field (VF) and best-corrected visual acuity (BCVA) scores were extracted and compared to assess changes. RESULTS:A total of 78 reports were retrieved and 6 studies involving 116 patients were included in the Meta-analysis. The combined results showed a significant decrease in logarithm of minimal angle of resolution (logMAR) scores, calculated using baseline and post-treatment BCVA (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I 2=36%) scores, which means there was considerable improvement in visual acuity. Meanwhile, more BCVA changes were observed in short-term (?6mo) treatment studies (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I 2=38%), studies conducted in Asia (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I 2=4%), studies with a sample size of 30 or fewer patients (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I 2=38%) and prospective studies (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I 2=0%). However, VPA's effect on VF was inconsistent across studies (P=0.75, mean difference=-22.76, 95%CI: -160.56, 115.05, I 2=68%). CONCLUSION:This Meta-analysis reveals that most RP patients who were treated with VPA showed improvement in BCVA. However, its effect on VF remains inconsistent. VPA may be a promising treatment for RP.
| S-EPMC6326947 | biostudies-other
Project description:PurposeTo investigate multimodal retinal imaging characteristics including the retinal nerve fiber layer (RNFL) thickness in patients with RPGR-associated retinitis pigmentosa (RP).MethodsThis cross-sectional case-control study included 17 consecutive patients (median age, 21 years) with RPGR-associated RP who underwent retinal imaging including optical coherence tomography (OCT), short-wavelength fundus autofluorescence (AF) imaging, and RNFL scans centered on the optic disc. RNFL thickness was manually segmented and compared to clinical and imaging parameters including the transfoveal ellipsoid zone (EZ) width, the horizontal diameter of the macular hyperautofluorescent ring. RNFL thickness was compared to 17 age- and sex-matched controls.ResultsIn patients with RPGR-associated RP, the EZ width (R2 = 0.65), the central hyperautofluorescent ring on AF images (R2 = 0.72), and visual acuity (R2 = 0.68) were negatively correlated with age. In comparison to controls, a significantly (p < 0.0001) increased global RNFL thickness was identified in RPGR-associated RP, which was, however, less pronounced in progressed disease as indicated by the EZ width or the diameter of the central hyperautofluorescent ring.ConclusionsThis study describes retinal characteristics in patients with RPGR-associated RP including a pronounced peripapillary RNFL thickness compared to healthy controls. These results contribute to the knowledge about imaging biomarkers in RP, which might be of interest for therapeutic approaches such as gene replacement therapies.
| S-EPMC8589744 | biostudies-literature