Retrospective Analysis of Structural Disease Progression in Retinitis Pigmentosa Utilizing Multimodal Imaging.
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ABSTRACT:
SUBMITTER: Cabral T
PROVIDER: S-EPMC5583352 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Retrospective Analysis of Structural Disease Progression in Retinitis Pigmentosa Utilizing Multimodal Imaging.
Cabral Thiago T Sengillo Jesse D JD Duong Jimmy K JK Justus Sally S Boudreault Katherine K Schuerch Kaspar K Belfort Rubens R Mahajan Vinit B VB Sparrow Janet R JR Tsang Stephen H SH
Scientific reports 20170904 1
In this report, we assess the natural progression rate of retinitis pigmentosa (RP) over an average of three years using spectral-domain optical coherence tomography (SD-OCT) and short wavelength fundus autofluorescence (SW-AF). Measurement of the ellipsoid zone (EZ) line width and hyperautofluorescent ring diameters was performed in 81 patients with RP in a retrospective, longitudinal fashion. Rate of structural disease progression, symmetry between eyes, and test-retest variability were quanti ...[more]
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Project description:We analyze disease progression in retinitis pigmentosa (RP) according to mode of inheritance by quantifying the progressive decrease of the ellipsoid zone (EZ) line width on spectral domain optical coherence tomography (SD-OCT) and of the dimensions of the hyperautofluorescent ring on short-wave fundus autofluorescence (SW-FAF). In this retrospective study of 96 patients, average follow-up time was 3.2 ± 1.9 years. EZ line width declined at a rate of -123 ± 8 µm per year, while the horizontal diameter and ring area declined at rates of -131 ± 9 µm and -0.5 ± 0.05 mm2 per year, respectively. Disease progression was found to be slowest for autosomal dominant RP and fastest for X-linked RP, with autosomal recessive RP progression rates between those of adRP and XLRP. EZ line width and ring diameter rates of disease progression were significantly different between each mode of inheritance. By using EZ line width and horizontal diameter as parameters of disease progression, our results confirm that adRP is the slowest progressing form of RP while XLRP is the fastest. Furthermore, the reported rates can serve as benchmarks for investigators of future clinical trials for RP and its different modes of inheritance.
| S-EPMC6656765 | biostudies-literature
Project description:To determine the rate of progression and optimal follow-up time in patients with advanced-stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral-domain optical coherence tomography.Retrospective analysis of progression rate.Longitudinal imaging follow-up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral-domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested.Significant progression was observed in >75% of patients during the 2-year mean follow-up. The mean annual progression rates of ellipsoid zone line and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45 degree (4.9%), 0.51 degree (4.1%), and 0.42 degree (4.0%), respectively. The ellipsoid zone line width and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5%, and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed.Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1-year intervals should be adequate to efficiently detect progression.
| S-EPMC4754981 | biostudies-literature
Project description:BackgroundTo determine the clinical characteristics and molecular genetic background responsible for USH2A mutations associated with nonsyndromic retinitis pigmentosa (RP) in five Chinese families, a retrospective cross-sectional study was performed.MethodsData on detailed history and comprehensive ophthalmological examinations were extracted from medical charts. Genomic DNA was sequenced by whole-exome sequencing. The pathogenicity predictions were evaluated by in silico analysis. The structural modeling of the wide-type and mutant USH2A proteins was displayed based on the I-Tasser software.ResultsThe ultra-wide-field fundus imaging showed a distinctive pattern of hyperautofluorescence in the parafoveal ring with macular sparing. Ten USH2A variants were detected, including seven missense mutations, two splicing mutations, and one insertion mutation. Six of these variants have already been reported, and the remaining four were novel. Of the de novo mutations, the p.C931Y and p.G4489S mutations were predicted to be deleterious or probably damaging; the p.M4853V mutation was predicted to be neutral or benign; and the IVS22+3A>G mutation was a splicing mutation that could influence mRNA splicing and affect the formation of the hairpin structure of the USH2A protein.ConclusionsOur data further confirm that USH2A protein plays a pivotal role in the maintenance of photoreceptors and expand the spectrum of USH2A mutations that are associated with nonsyndromic RP in Chinese patients.
| S-EPMC7667352 | biostudies-literature
Project description:PurposeVariants in PRPF31, a splicing factor, are a common cause of autosomal dominant retinitis pigmentosa (RP). Deleterious variants are thought to cause disease by haploinsufficiency. In anticipation of upcoming replacement gene therapy trials, we present the phenotype and clinical progression of a large cohort of patients with PRPF31-mediated RP.DesignCross-sectional with retrospective review.MethodsA total of 26 patients with RP and 5 asymptomatic individuals, all with deleterious variants in PRPF31 (from 13 families), were selected from our database of patients followed longitudinally. Ages ranged from 9 to 77 years (mean 47 years), with an average follow-up time of 16 years. All patients underwent ophthalmic examination including psychophysical tests, electrophysiology, and imaging. All available records were reviewed retrospectively. Additionally, all patients were contacted, and all available patients (n = 7) were examined in an additional prospective follow-up visit.ResultsAge of onset ranged from 6 to 71 years, without apparent relationship to specific variant. Two adults (aged 42 and 77 years) and 3 teenaged children were found to harbor a mutation with no evidence of RP. In those with RP, visual field area (spot size III) declined exponentially at a rate of 8.1% per year of disease duration (P < .001, 95% confidence interval [CI] 5.6-10.6), cone electroretinogram amplitude declined exponentially at a rate of 7.3% per year of disease duration (P < .001, 95% CI 5.4-9.1), and ellipsoid zone area declined exponentially at a rate of 5.4% per year of disease duration (P < .001, 95% CI 3.7-7.1).ConclusionsPRPF31-mediated retinitis pigmentosa is characterized by a variable age of onset. Once disease develops, it follows a predictable exponential time course.
| S-EPMC6481169 | biostudies-literature
Project description:Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.
| S-EPMC3131731 | biostudies-literature
Project description:PURPOSE:To report an unusual phenotype of retinitis pigmentosa (RP) caused by compound heterozygous mutations in SPATA7, and describe the progression over a two year follow-up period. METHODS:Retrospective case study. RESULTS:A 63-year-old man with a long history of nyctalopia, progressive visual field constriction, and a recent subacute decrease in visual acuity of the left eye presented for evaluation of a suspected retinal degeneration. Multimodal retinal imaging and functional assessment with full-field electroretinogram suggested a severe rod-cone dysfunction masquerading as a choroideremia-like phenotype. A vitreous opacity was found to explain recent changes in the left eye and a 25-guage vitrectomy and membrane peel was performed, yielding no change in visual acuity. Whole-exome sequencing revealed compound heterozygous variants in SPATA7 that were predicted to be pathogenic. CONCLUSIONS:Compound heterozygous c.1100A > G, p.(Y367C) and c.1102_1103delCT, p.(L368Efs*4) variants in SPATA7 manifest as an unusual RP phenotype in this case, showing extensive choroidal sclerosis and retinal pigment epithelium (RPE) atrophy with evidence of progression over two years on multimodal imaging.
| S-EPMC6015729 | biostudies-literature
Project description:PurposeThe purpose of this study was to investigate the genetic and clinical characteristics of eyes shut homolog (EYS)-associated retinitis pigmentosa (RP).MethodsThis was a retrospective cross-sectional observational study of 36 patients with EYS-associated autosomal recessive RP (arRP).ResultsThe gene sequencing results revealed that c.6416G>A (p.Cys2139Tyr) and c.7228+1G>A were the two most predominant variants in our cohort and that variants near the C-terminus, which contains alternating laminin and epidermal growth factor (EGF) domains, accounted for the majority of the allele counts (58 of a total of 72) and relative allele frequencies (81%). Over half of the patients presented with pericentral-type RP (n = 19, 60%), which frequently occurred in combination with macular lesions (n = 10, 52%). Patients having both variants within the alternating laminin and EGF domains near the C-terminus had a more severe disease progression (average 0.045 logMAR increase per year) than those having one variant in the N-terminus and the other in the C-terminus (average 0.001 logMAR increase per year).ConclusionsPericentral RP was the major phenotype in patients with EYS-associated arRP. There was also a statistically significant relationship between the location of the variants and the severity of the disease.Translational relevanceThis study may aid patients with EYS-associated arRP to predict future vision acuity based on their genetic and clinical features.
| S-EPMC9284463 | biostudies-literature
Project description:PurposeTo quantitatively compare near-infrared autofluorescence (NIR-AF) and short-wave autofluorescence (SW-AF) as imaging modalities used to monitor retinitis pigmentosa (RP) disease progression, measured as a function of hyperautofluorescent ring constriction over time.DesignRetrospective cohort study.MethodsNIR-AF and SW-AF images were acquired from 22 participants (44 eyes) at 2 clinic visits separated by an average of 2 years. On the images from each modality, the horizontal and vertical diameters and area of the hyperautofluorescent rings were measured twice, 2 weeks apart. A progression rate for each parameter was obtained. Descriptive and comparative statistics were calculated to analyze these parameters and their respective progression rates.ResultsAt both visits, the hyperautofluorescent ring exhibited a larger horizontal diameter (both visits: P < .001), vertical diameter (visit 1: P < .001, visit 2: P = .040), and ring area (visit 1: P = .001, visit 2: P = .011) in SW-AF vs NIR-AF images. In SW-AF, the horizontal diameter, vertical diameter, and ring area decreased yearly by 168 ± 204 μm, 131 ± 159 μm, and 0.7 ± 1.1 mm2, respectively, while in NIR-AF, they decreased by 151 ± 156 μm, 135 ± 190 μm, and 0.7 ± 1.0 mm2. No difference was observed in these rates between SW-AF and NIR-AF. Similar results were observed in the left eye.ConclusionsIn SW-AF and NIR-AF images, similar rates of RP disease progression are observed. As such, NIR-AF may confer more advantages as the primary tool for tracking disease progression over the commonly used SW-AF, given the increased patient comfort and cooperation during imaging.
| S-EPMC6165697 | biostudies-literature
Project description:Optical coherence tomography angiography (OCT-A) is a non-invasive alternative to fluorescein angiography that allows for the study of the retinal and choroidal vasculatures. In this retrospective cohort study of 28 patients with retinitis pigmentosa (RP), we used OCT-A to quantify changes in perfusion density, foveal avascular zone (FAZ) area, and choriocapillaris blood flow over time and correlated these variables with ellipsoid zone (EZ) line width and best-corrected visual acuity (BCVA). Perfusion density decreased by 2.42?±?0.62% per year at the superior capillary plexus (SCP) (P?=?0.001) and 2.41?±?0.76% per year at the deep capillary plexus (DCP) (P?=?0.004). FAZ area increased by 0.078?±?0.021 mm2 per year (P?=?0.001) at the SCP and 0.152?±?0.039 mm2 per year (P?=?0.001) at the DCP. No changes were observed in the choriocapillaris blood flow. EZ line width had the strongest correlation to perfusion density at the SCP (r?=?0.660 and 0.635, first and second visit, respectively, P?=?0.001), while BCVA most strongly correlated with FAZ area at the SCP (r?=?0.679 and 0.548, P?=?0.001 and 0.003). Our results suggest that OCT-A is a useful tool for monitoring RP disease progression and may be used to measure retinal vascular parameters as outcomes in clinical trials.
| S-EPMC6120860 | biostudies-other
Project description:Due to the genotype-phenotype heterogeneity in retinitis pigmentosa (RP), molecular diagnoses and prediction of disease progression is difficult. This study aimed to report ocular and genetic data from Korean patients with PDE6B-associated RP (PDE6B-RP), and establish genotype-phenotype correlations to predict the clinical course. We retrospectively reviewed targeted next-generation sequencing or whole exome sequencing data for 305 patients with RP, and identified PDE6B-RP in 15 patients (median age, 40.0 years). Amongst these patients, ten previously reported PDE6B variants (c.1280G > A, c.1488del, c.1547T > C, c.1604T > A, c.1669C > T, c.1712C > T, c.2395C > T, c.2492C > T, c.592G > A, and c.815G > A) and one novel variant (c.712del) were identified. Thirteen patients (86.7%) experienced night blindness as the first symptom at a median age of 10.0 years. Median age at diagnosis was 21.0 years and median visual acuity (VA) was 0.20 LogMAR at the time of genetic analysis. Nonlinear mixed models were developed and analysis revealed that VA exponentially decreased over time, while optical coherence tomography parameters linearly decreased, and this was related with visual field constriction. A high proportion of patients with the c.1669C > T variant (7/9, 77.8%) had cystoid macular edema; despite this, patients with this variant did not show a higher rate of functional or structural progression. This study will help clinicians predict functional and structural progression in patients with PDE6B-RP.
| S-EPMC7658990 | biostudies-literature