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Purpose: To examine whether the extension of retinal pigment epithelium (RPE) and outer retinal atrophy (RORA) and various other morphofunctional parameters correlate with the genetic assessment and severity of retinitis pigmentosa (RP)., Methods: Thirty-eight patients (76 eyes) with RP were prospectively enrolled and underwent full ophthalmic examination, including visual field testing, full-field electroretinography (ERG), and optical coherence tomography angiography. The severity of the disease was calculated using the RP stage scoring system, and the area of RORA was assessed using the automatically calculated area of sub-RPE illumination. Blood or saliva samples were collected from subjects, and DNA extraction was performed to evaluate genetic mutations and nucleotide and amino acid variations., Results: There was a statistically significant correlation between the extent of RORA and patient age, best-corrected visual acuity, ellipsoid zone extension, and disease severity in both eyes (each, P < 0.05). In contrast, RORA did not correlate with either the visual field or the ERG amplitude. Cumulative score and grade severity were both significantly correlated with superficial and deep capillary plexus density (both, P < 0.001) in both eyes. Evaluating RORA, we found genes with an overall less severe phenotype, such as EYS, PCDH15, and PRPF31, and those with a worse phenotype, such as RPGR., Conclusions: The correlation of RORA with structural, functional, and genetic assessment in RP disease leads us to consider RORA as a potential biomarker for prediction of disease stage. Multicenter studies are needed to confirm our findings., Translational Relevance: The morphofunctional and genetic correlations suggest a role for RORA in RP diagnosis and follow-up.

The aim of this paper is to investigate whether a multifractal analysis can be applied to study choroidal blood vessels and help ophthalmologists in the early diagnosis of retinitis pigmentosa (RP). In a case study, we used spectral domain optical coherence tomography (SDOCT), which is a noninvasive and highly sensitive imaging technique of the retina and choroid. The image of a choroidal branching pattern can be regarded as a multifractal. Therefore, we calculated the generalized Renyi point-centered dimensions, which are considered a measure of the inhomogeneity of data, to prove that it increases in patients with RP as compared to those in the control group.

Retinitis pigmentosa (RP) is a group of inherited rod-cone dystrophies, noted for a high genotypical and phenotypical heterogeneity.Traditionally, VA, visual field, and electroretinography have been used to assess RP progression. However, visual acuity and visual field tests are essentially subjective and, especially in the late stages of the disease, are unable to confidently reveal minor progression. Therefore, there is a need for novel examination modalities that rely on quantitative, structural measurements. In this regard, several non-invasive imaging techniques have been studied, including spectral-domain optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. By correlating surrogate biomarkers with functional measurements of the disease, these techniques may be able to develop reliable outcome meters that can be used to gain a deeper understanding of the underlying causes of the disease and to assess the effectiveness of therapy even before an actual loss of vision occurs.In this review, we will summarize the recent imaging findings and biomarkers that have been identified in RP patients. Our goal is to provide information that can promptly aid in selecting patients for clinical trials and new gene therapies, monitoring the disease progression, and evaluating treatment outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 μm; moderate, < 2500 μm; advanced, absence. Using optical coherence tomography angiography, quantitative microvascular parameters were analyzed. In total, 91 eyes from 49 patients were included. For the superficial capillary plexus (SCP) and deep capillary plexus (DCP), perfusion densities (PDs) in the early stage (SCP: 37.32 ± 8.11%; DCP: 21.19 ± 9.15%) were greater than those in moderate (SCP: 34.16 ± 6.65%, P = 0.011; DCP: 15.67 ± 8.85%, P = 0.031) and advanced stages (SCP: 33.71 ± 9.02%, P = 0.030; DCP: 12.83 ± 6.29%, P < 0.001). The choroidal vascularity index in the early stage (0.58 ± 0.03) was greater than those in the moderate (0.57 ± 0.02, P = 0.017) and advanced stage (0.56 ± 0.02, P = 0.033). The area and perimeter of foveal avascular zone (FAZ) in advanced stage (0.44 ± 0.26 mm 2 , 2.96 ± 0.86 mm, respectively) were larger than those in early (0.26 ± 0.11 mm 2 , P = 0.020; 2.19 ± 0.53 mm, P = 0.006, respectively) and moderate stage (0.28 ± 0.13 mm 2 , P = 0.043; 2.24 ± 0.67 mm, P = 0.013, respectively). During RP disease progression, retinal and choroidal microvascular vessel density decreases in the early stage, followed by FAZ enlargement in the advanced stage., (© 2024. The Author(s).)

Objective: Cystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera., Methods: We retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME., Results: We evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm2, and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME., Conclusion: Complications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kitahata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: The Suprachoroidal Space (SCS) is a theoretical structure which can be demonstrated between the inner border of the sclera and the outer boundary of the choroid. SCS is being studied for its potential uses as a route for drug delivery and innovative surgical techniques for the treatment of many retinal diseases. Retinitis pigmentosa (RP) is a group of inherited eye disorders characterized by a gradual loss of photoreceptors, resulting in vision impairment, which typically presents as night blindness and progressive visual field loss. The purpose of the study is to define the morphology of outer choroidal margins by means of SS-OCT in RP., Material and Method: This is a retrospective observational study designed to evaluate the presence of SCS in RP. We performed Swept Source optical coherence tomography (SS-OCT) in a group of 55 patients affected by RP (26 males and 29 females, 110 eyes) with a mean age of 51.8 ± 13.7 years. In the control group, we included 28 healthy subjects (6 males and 22 females, 56 eyes) with a mean age of 48,8 ± 16,6 years., Results: OCT scans allowed the outer choroidal margin and inner scleral margin to be delineated with certainty in all 110 eyes. In the RP group SCS was detected in 47 of 110 eyes (42,7%), in the control group SCS was detected in 11 eyes (19,6%). Subjects with SCS visible (RP group) had reduced retinal thickness (168.4 µm) compared to those with not visible SCL (211.2 µm, P = .007)., Conclusions: SS-OCT can be successfully applied to assess the presence of SCS in RP and the high rate of SCS found in the RP patients is encouraging when considering future innovative therapies., (Copyright © 2023 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: In this study, we aimed to evaluate macular perfusion with optical coherence tomography angiography (OCTA) and to investigate the correlation between OCTA quantitative data and visual acuity (VA) in patients with retinitis pigmentosa (RP)., Methods: This retrospective single-center study was conducted on 60 eyes of 30 RP patients and 52 healthy eyes. The vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula, the size of foveal avascular zone (FAZ), choriocapillary flow density (FD) were measured using OCTA. Quantitative data obtained with OCTA were compared between the two groups. In addition, the correlation between the OCTA measurements and VA was examined., Results: In patients with RP, the choriocapillary FD was decreased (p = 0.001), the FAZ area was enlarged (p = 0.010), and the VDs of the SCP and DCP were decreased in all areas (p = 0.001). Correlation was found between VA and SCP VD, whole image (p = 0.011, rho = -0.327) and parafoveal (p = 0.001, rho = -0.444) areas., Conclusion: Quantitative data from OCTA showed reduced macular perfusion in patients with RP compared to healthy controls. There was also a correlation between the quantitative OCTA data and VA., Competing Interests: Declaration of Competing Interest The author(s) declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Optical coherence tomography (OCT) is a noninvasive, frequently used imaging technology that enables detailed viewing of retina anatomy. It is used to monitor disease progression in retinitis pigmentosa (RP) eyes, including detecting changes in retinal thickness., Purpose: The purpose of the study is to determine the clinical presentation and macular morphology in RP eyes using OCT imaging., Methods: A retrospective review of case records and OCT scans in eyes diagnosed with RP in two ophthalmic clinics in Nigeria. Biodata, Snellen best-corrected visual acuity (BCVA), intraocular pressure (IOP), vertical cup-to-disc ratio (VCDR), and presence of maculopathy were determined. Data were analyzed using IBM SPSS version 22.0 (IBM Corp. Armonk, NY, USA)., Results: Fifty-five eyes of 28 patients (18 males and 10 females), with a mean age of 47.16 ± 15.56 years (22-77 years), were studied. 40-49 years was the most frequent age group, 28.6%. Severe visual impairment occurred in 22% of eyes and myopia in 32%. Twenty-nine percent had undergone cataract surgery or had a significant cataract. The mean IOP was 11 mmHg, and the mean VCDR was 0.46. On OCT examination, macular atrophy was the most common finding in 74.5% of eyes, epiretinal membrane in 16.3%, cystoid macular edema in 7.3%, vitreomacular adhesion in 5.4%, and vitreomacular traction in 1.8%. There was no association between macular morphology, macular thickness, and BCVA (P = 0.155, P = 0.424)., Conclusion: OCT provides information on macula structure in RP eyes. About 14.5% of eyes had a normal macula, while 85.5% had a maculopathy, confirming that RP eyes have a higher rate of maculopathy than non RP eyes. OCT evaluation of an RP eye should be a standard workup for the early detection of such maculopathy and monitoring for disease progression., Competing Interests: None

This retrospective study identifies patients with RP at the Inherited Retinal Disease Clinic at the University of Minnesota (UMN)/M Health System who had genetic testing via next generation sequencing. A database was curated to record history and examination, genetic findings, and ocular imaging. Causative pathogenic and likely pathogenic variants were recorded. Disease status was further characterized by ocular coherence tomography (OCT) and fundus autofluorescence (AF). Our study cohort included a total of 199 patients evaluated between 1 May 2015-5 August 2022. The cohort included 151 patients with non-syndromic RP and 48 with syndromic RP. Presenting symptoms included nyctalopia (85.4%) photosensitivity/hemeralopia (60.5%), and decreased color vision (55.8%). On average, 38.9% had visual acuity of worse than 20/80. Ellipsoid zone band width on OCT scan of less than 1500 μm was noted in 73.6%. Ninety-nine percent had fundus autofluorescence (AF) findings of a hypo- or hyper-fluorescent ring within the macula and/or peripheral hypo-AF. Of the 127 subjects who underwent genetic testing, a diagnostic pathogenic and/or likely pathogenic variant was identified in 67 (52.8%) patients-33.3% of syndromic RP and 66.6% of non-syndromic RP patients had a diagnostic gene variant identified. It was found that 23.6% of the cohort had negative genetic testing results or only variants of uncertain significance identified, which were deemed as non-diagnostic. We concluded that patients with RP often present with advanced disease. In our population, next generation sequencing panels identified a genotype consistent with the exam in just over half the patients. Additional work will be needed to identify the underlying genetic etiology for the remainder.

Aims: To describe the changes in vessel density (VD) using optical coherence tomography angiography (OCTA) of the different sectors in the macular area between retinitis pigmentosa (RP) patients and controls., Methods: Observational case-control study. We initially included 22 patients with RP and 21 controls. We obtained 6 × 6 OCTA images of the macular area using Angio-OCT SS-DRI-Triton 1.22 (Topcon, Japan), together with visual acuity, biomicroscopy, visual field and optical coherence tomography examination. We compared the VD values in both groups for both superficial (SVP) and deep vascular plexus (DVP). Correlation between VD and macular thickness was also calculated., Results: The mean visual field index (VFI) in the RP group was 26.11% (±17.29). VD was significantly lower in the RP group compared with healthy controls in all sectors of the DVP (Superior 43.48 ± 3.79 vs 48.86 ± 2.62, P < .0001; Nasal 40,52 ± 4.30 vs 46,01 ± 3.23, P = .0002; Inferior 42.76 ± 5.26 vs 50.10 ± 3.36, P < .0001; Temporal 40.42 ± 4.46 vs 46.09 ± 2.91, P = .0001) and in all but nasal sector in the SVP (Superior 39.86 ± 4.46 vs 46.47 ± 2.61, P < .0001; Nasal 40.35 ± 4.56 vs 44.09 ± 2.87, P = .0067; Inferior 40.74 ± 4.61 vs 46.58 ± 3.26, P = .0002; Temporal 39.98 ± 5.07 vs 44.78 ± 3.28, P = .0024). Correlation between VD and macular thickness was positive and significant (RP: r = 0.59, P = .043; controls r = 0.51, P = .018)., Conclusions: Patients with advanced forms of RP have less vessel density in the macular area than healthy subjects. These differences are present in all four quadrants in the DVP and three in the SVP., (Copyright © 2023 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

The aim of the study was to characterize macular edema (ME) in retinitis pigmentosa (RP) by means of quantitative optical coherence tomography (OCT)-based imaging. The study was designed as observational, prospective case series, with 1-year follow-up. All RP patients underwent complete ophthalmologic assessment, including structural OCT, OCT angiography, and microperimetry (MP). The primary outcome was the characterization through quantitative OCT-based imaging of RP eyes complicated by ME. A total of 68 RP patients' eyes (68 patients) and 68 eyes of 68 healthy controls were recruited. Mean BCVA was 0.14 ± 0.17 LogMAR at baseline and 0.18 ± 0.23 LogMAR at 1-year follow-up (p > 0.05). Thirty-four eyes (17 patients; 25%) showed ME, with a mean ME duration of 8 ± 2 months. Most of the eyes were characterized by recurrent ME. The ME was mainly localized in the inner nuclear layer in all eyes. LogMAR BCVA was similar in all RP eyes, whether with or without ME, although those with ME were associated with higher vessel density values, as well as thicker choroidal layers, than those without ME. In conclusion, the inner retina is closely involved in the pathogenesis of ME. The impairment of retinal-choroidal exchanges and Müller cell disruption might be a major pathogenic factor leading to the onset of ME in RP., (© 2023. The Author(s).)

The development of fundus photography and imaging has improved our ability to diagnose and monitor inherited retinal degenerations. Nowadays, color fundus photography has become a staple in evaluating patients with retinitis pigmentosa (RP). Other important multimodal forms of fundus photography used today include red-free fundus photography, short-wavelength autofluorescence, and near-infrared autofluorescence. These photography methodologies provide valuable information on the natural history of disease progression, which in turn can lead to the identification of viable outcome measurements for current and future therapeutic trials. Further advances and developments in the field of fundus imaging will help in our understanding of RP and allied disorders., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Optical coherence tomography (OCT) is a noninvasive imaging technology that has gained widespread use in the evaluation of multiple retinal pathologies, including retinitis pigmentosa (RP). OCT allows for visualization of distinct retinal layers and the choroid and facilitates study of morphological features associated with RP. OCT can be used to detect and to track progression of RP, as well as to correlate structural findings with functional manifestations of the disease. This chapter provides a basic overview of OCT technology and details elements of importance in the use of OCT for diagnosis and assessment of progression of RP., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Optical coherence tomography angiography (OCTA) is a noninvasive new imaging modality that can be used to diagnose and monitor progression of retinitis pigmentosa (RP). Cohorts and case series have shown correlation between OCTA findings and visual function and disease severity. Although an early use of the technology is promising, there are concerns about segmentation errors and artifacts. There is also a paucity of data on genotype and how that correlates with OCTA findings. Despite its limitations, OCTA remains a useful tool for clinicians managing retinitis pigmentosa patients., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate and compare the vessel density (VD) using swept-source optical coherence tomography angiography (OCT-A) and the choroidal vascularity index (CVI) using spectral-domain optical coherence tomography (SD-OCT) in patients with Bietti crystalline dystrophy (BCD) and retinitis pigmentosa (RP)., Materials and Methods: A cross-sectional retrospective study was conducted on 26 eyes of 13 BCD patients, 26 eyes of 13 RP patients, and 26 eyes of 13 age- and gender-matched healthy individuals. BCD patients were further staged as having early, intermediate, and advanced disease. VD was assessed in five quadrants of the macula (superior, temporal, inferior, nasal, and center) using a modified ETDRS technique with OCT-A. SD-OCT scans were binarized using Niblack's autolocal threshold, and CVI was determined as the ratio of the luminal area to the total choroidal area., Results: A significant difference was found in VD in all quadrants of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) slabs among the three groups (p < 0.001). A statistically significant difference was noted in the mean VD of temporal and inferior quadrants of the SCP and between the BCD and RP groups (p = 0.005, p = 0.015, respectively). A statistically significant difference was observed in the mean VD of the temporal, inferior, and nasal quadrants between the BCD and RP groups on DCP slabs (p = 0.002, p = 0.003, p = 0.003, respectively). The mean central choroidal thickness was 214.65±87.10 μm in the BCD group, 351.69±67.94 μm in the RP group, and 320.92±59.26 μm in the control group (p < 0.001). We found that CVI was significantly higher in the control group than BCD group (p < 0.001), and it was significantly lower in the BCD group when compared to the RP group (p < 0.001).There was no difference in CVI between RP and control groups (p = 0.948). Furthermore, the CVI was significantly lower in the intermediate and advanced disease stages than the early disease stage in the subgroup analysis of BCD patients (p < 0.001, p < 0.001, respectively)., Conclusion: CVI is a novel investigative tool to monitor disease progression. The CVI value was lower in BCD and RP patients than in the healthy subjects, and lower CVI values seem to be related to the disease severity in BCD patients. VD was also significantly lower in BCD patients when compared to RP patients, and VD analysis may help clinicians better understand the disease pathophysiology., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP-induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy ( 1 H-MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N-acetylaspartate (NAA), glutamate (Glu), γ-aminobutyric acid (GABA), and taurine (Tau), whereas myo-inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p < 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p < 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p < 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p = 0.005). Meanwhile, the 1 H-MRS indicators in 5-month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes., (© 2022 John Wiley & Sons Ltd.)

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive rod and cone photoreceptor degeneration. Changes in retinal vasculature have long been associated with RP. Optical coherence tomography angiography (OCTA) is a novel imaging technology that enables noninvasive visualization of the retinal and choroidal microvasculature. OCTA enables quantification of microvascular changes in the retinal capillary plexus and choriocapillaris, in addition to qualitative feature description. Therefore, OCTA has the potential to become an important tool for better understanding, early detection, progression, and treatment of RP. In this review, we focus on the applications of OCTA in clinical research on RP. We also discuss future improvements in the OCTA technology for RP management. We believe that the advancement of the OCTA technique will ultimately lead to a better understanding of RP and aid in the prevention of visual impairment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The purpose of this study was to establish spectral domain optical coherence tomography (SD-OCT) assessment data in well-established canine models of inherited retinal dystrophies: PDE6B-rod-cone dysplasia 1 (RCD1: early onset retinitis pigmentosa), PRCD-progressive rod-cone degeneration (PRCD: late onset retinitis pigmentosa), CNGB3-achromatopsia, and RPE65-Leber congenital amaurosis (LCA). High resolution SD-OCT images of the retina were acquired from both eyes in 5 planes: temporal; superotemporal; superior; nasal; and inferior in adult dogs with: RCD1 (n = 4 dogs, median age: 1.5 yrs); PRCD (n = 2, 4.3 yrs); LCA (n = 3, 5.2 yrs); achromatopsia (n = 3, 4.2 yrs); and wild types (wt, n = 6, 5.5 yrs). Total, inner and outer retinal thicknesses and ellipsoid zone were analyzed. In selected animals, histomorphometric evaluations were performed. In dogs with RCD1, PRCD, and LCA, the thickness of the outer retina was, compared to wt, significantly decreased (p ≤ 0.02) in all OCT imaging planes, and in superotemporal and inferior imaging planes in dogs with achromatopsia. No significant thinning was observed in inner retina thickness in any disease model except in the inferior imaging plane in dogs with RCD1. Dogs with RCD1, PRCD, and LCA had significantly more areas with disrupted ellipsoid zone in the presumed area centralis than wt (p ≤ 0.001). OCT findings provide baseline information for research of retinal dystrophies using these canine models., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in patients with retinitis pigmentosa (RP) using entropy measurements by custom-made polarization-sensitive optical coherence tomography (PS-OCT) images, and compare entropy with the intensity of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF). We retrospectively reviewed the retinal images, including PS-OCT, SW-AF, and NIR-AF of patients with RP who had a hyperautofluorescent ring on AF. A total of 12 eyes of 12 patients (8 women and 4 men; mean age: 37.9 years) were included. There was a strong positive correlation between entropy value and NIR-AF intensity (r = 0.626, p < 0.001), and there was a very weak negative correlation between entropy value and SW-AF (r = - 0.197, p = 0.001). The mean values of the entropy in the foveal, temporal (2 mm from the fovea), and nasal (2 mm from the fovea) sections were 0.41 (± 0.09), 0.29 (± 0.08), and 0.26 (± 0.08), respectively. The entropy was significantly higher in the foveal section than in the temporal and nasal sections (p = 0.002 and p = 0.003, respectively). There was no significant difference between the entropies values for the temporal and nasal sections (p = 0.157). Age, logMAR best-corrected visual acuity, ellipsoid zone width, and central retinal thickness were not correlated with foveal entropy. We presented RPE melanin imaging in patients with RP using PS-OCT for the first time. PS-OCT can be a useful tool for monitoring patients with RP., (© 2022. The Author(s).)

Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography underlying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diameter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial alignment was observed between IR-EZ and OR-ELM diameters/widths (p < 0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 μm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p < 0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p < 0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint.

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has been used for imaging retinitis pigmentosa (RP) eyes and provides useful information on microstructural changes., Aim: To review SD-OCT findings and correlate the central foveal thickness (CFT), outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ) with visual function in nonsyndromic RP eyes., Patients and Methods: A multicenter, retrospective review of records from consecutive eyes diagnosed to have RP. Biodata, systemic disease, visual acuity, lens status, intraocular pressure, and SD-OCT images were examined. The CFT was categorized into normal (250-299 microns), atrophic (0-249 microns), and edematous (≥300 microns). The ONL, ELM, and EZ within the subfoveal area was assessed and rated as normal, reduced (if less than normal), or absent (if missing). The status of these biomarkers was correlated with visual acuity and statistical analysis performed using Pearson Chi 2 , P < 0.05. In addition, the vitreomacular interface was examined for the presence of vitreomacular traction (VMT), vitreomacular adhesion (VMA), and epiretinal membrane (ERM)., Results: Fifty-two RP eyes of 27 patients had SD-OCT images that were used for study analysis. There were 17 males and 10 females; 52% of participants were between 31 and 50 years (age range: 22-77 years). An atrophic retina was the most common finding in 42 eyes (81%); the average CFT in the atrophic group was 175 microns (range: 111-245 microns). There were three eyes with cystoid macular edema, and seven eyes were normal. For the OCT biomarkers, a reduction in ONL and ELM occurred in 69% and 46% of eyes, respectively, while an absence was the most common EZ finding (in 50% of eyes). There was a significant correlation between the presence or absence of the three biomarkers and presenting vision: ONL, ELM, and EZ with P values of 0.000, 0.006, and 0.011, respectively. The CFT had no significant correlation with vision; P = 0.522. Other findings on OCT include ERM 17%, VMA 6%, and VMT 2%., Conclusion: This report supports the notion that OCT image reporting on physical retinal structure in RP eyes can be used to predict disease effects on vision. A prospective study to better quantify the degree of structural change and correlate with the degree of functional loss is required for RP gene types in Nigerians and black Africans., Competing Interests: None

Purpose: Mer tyrosine kinase-retinitis pigmentosa ( MERTK- RP) causes a primary defect in the retinal pigment epithelium, which subsequently affects rod and cone photoreceptors. The study aims to identify the most appropriate MERTK -RP biomarkers to measure disease progression for deciding the optimum therapeutic trial intervention time., Materials and Methods: Patients' data from baseline (BL) and last follow-up (LFU) were reviewed. Best corrected visual acuity (BCVA), spectral domain-optical coherence tomography (SD-OCT), ultra-widefield fundus autofluorescence (UWF-FAF) patterns, kinetic perimetry (KP), and electroretinography (ERG) parameters were analyzed., Results: Five patients were included with the mean age of 17.7 ± 14.4 years old (6.7-42.3) at BL and mean BCVA follow-up of 8.4 ± 5.1 years. Mean BCVA at BL and LFU were 0.84 ± 0.86 LogMAR and 1.14 ± 0.86 LogMAR, respectively. The BCVA decline rate was 0.05 ± 0.03 LogMAR units/year. Ellipzoid zones (EZ) were measurable in eight eyes with mean BL length of 1293.75 ± 421.07 µm and reduction of 140.95 ± 69.28 µm/year and mean BL CMT of 174.2 ± 37.52 µm with the rate of 11.2 ± 12.77 µm declining/year. Full-field ERG (ffERG) and pattern ERG (pERG) were barely recordable. UWF-FAF showed central macular hyper-autofluorescence (hyperAF). KP (III4e and V4e) was normal in two eyes, restricted nasally in four eyes, superior wedge defect in two eyes and undetectable in two eyes. The four restricted nasally KPs became worse, while the others stayed almost unchanged., Conclusions: This cohort showed early visual loss, moderately rapid EZ reduction and macular hyperAF. EZ, CMT, and BCVA were consistently reduced. Relative rapid decline in these biomarkers reflecting visual function suggests an early and narrow timespan for intervention.

Purpose: We propose and evaluate a hybrid model composed of two convolutional neural networks (CNNs) with different architectures for automatic segmentation of retina layers in spectral domain optical coherence tomography (SD-OCT) B-scans of retinitis pigmentosa (RP)., Methods: The hybrid model consisted of a U-Net for initial semantic segmentation and a sliding-window (SW) CNN for refinement by correcting the segmentation errors of U-Net. The U-Net construction followed Ronneberger et al. (2015) with an input image size of 256 × 32. The SW model was similar to our previously reported approach. Training image patches were generated from 480 horizontal midline B-scans obtained from 220 patients with RP and 20 normal participants. Testing images were 160 midline B-scans from a separate group of 80 patients with RP. The Spectralis segmentation of B-scans was manually corrected for the boundaries of the inner limiting membrane, inner nuclear layer, ellipsoid zone (EZ), retinal pigment epithelium, and Bruch's membrane by one grader for the training set and two for the testing set. The trained U-Net and SW, as well as the hybrid model, were used to classify all pixels in the testing B-scans. Bland-Altman and correlation analyses were conducted to compare layer boundary lines, EZ width, and photoreceptor outer segment (OS) length and area determined by the models to those by human graders., Results: The mean times to classify a B-scan image were 0.3, 65.7, and 2.4 seconds for U-Net, SW, and the hybrid model, respectively. The mean ± SD accuracies to segment retinal layers were 90.8% ± 4.8% and 90.7% ± 4.0% for U-Net and SW, respectively. The hybrid model improved mean ± SD accuracy to 91.5% ± 4.8% (P < 0.039 vs. U-Net), resulting in an improvement in layer boundary segmentation as revealed by Bland-Altman analyses. EZ width, OS length, and OS area measured by the models were highly correlated with those measured by the human graders (r > 0.95 for EZ width; r > 0.83 for OS length; r > 0.97 for OS area; P < 0.05). The hybrid model further improved the performance of measuring retinal layer thickness by correcting misclassification of retinal layers from U-Net., Conclusions: While the performances of U-Net and the SW model were comparable in delineating various retinal layers, U-Net was much faster than the SW model to segment B-scan images. The hybrid model that combines the two improves automatic retinal layer segmentation from OCT images in RP., Translational Relevance: A hybrid deep machine learning model composed of CNNs with different architectures can be more effective than either model separately for automatic analysis of SD-OCT scan images, which is becoming increasingly necessary with current high-resolution, high-density volume scans.

Photoreceptor degeneration caused by genetic defects leads to retinitis pigmentosa, a rare disease typically diagnosed in adolescents and young adults. In most cases, rod loss occurs first, followed by cone loss as well as altered function in cells connected to photoreceptors directly or indirectly. There remains a gap in our understanding of retinal cellular responses to photoreceptor abnormalities. Here, we utilized single-cell transcriptomics to investigate cellular responses in each major retinal cell type in retinitis pigmentosa model (P23H) mice vs. wild-type littermate mice. We found a significant decrease in the expression of genes associated with phototransduction, the inner/outer segment, photoreceptor cell cilium, and photoreceptor development in both rod and cone clusters, in line with the structural changes seen with immunohistochemistry. Accompanying this loss was a significant decrease in the expression of genes involved in metabolic pathways and energy production in both rods and cones. We found that in the Müller glia/astrocyte cluster, there was a significant increase in gene expression in pathways involving photoreceptor maintenance, while concomitant decreases were observed in rods and cones. Additionally, the expression of genes involved in mitochondrial localization and transport was increased in the Müller glia/astrocyte cluster. The Müller glial compensatory increase in the expression of genes downregulated in photoreceptors suggests that Müller glia adapt their transcriptome to support photoreceptors and could be thought of as general therapeutic targets to protect against retinal degeneration., (© 2021. The Author(s).)

Background: Joubert syndrome (JS) is a group of rare congenital disorders characterized by cerebellar vermis dysplasia, developmental delay, and retina dysfunctions. Herein, we reported a Chinese patient carrying a new variant in the AHI1 gene with mild JS, and the 3D structure of the affected Jouberin protein was also predicted., Case Presentation: The patient was a 31-year-old male, who presented difficulty at finding toys at the age of 2 years, night blindness from age of 5 years, intention tremor and walking imbalance from 29 years of age. Tubular visual field and retina pigmentation were observed on ophthalmology examinations, as well as molar tooth sign on brain magnetic resonance imaging (MRI). Whole exome sequence revealed two compound heterozygous variants at c.2105C>T (p.T702M) and c.1330A>T (p.I444F) in AHI1 gene. The latter one was a novel mutation. The 3D protein structure was predicted using I-TASSER and PyMOL, showing structural changes from functional β-sheet and α-helix to non-functional D-loop, respectively., Conclusions: Mild JS due to novel variants at T702M and I444F in the AHI1 gene was reported. The 3D-structural changes in Jouberin protein might underlie the pathogenesis of JS., (© 2021. The Author(s).)

In contrast to USH2A , variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in terms of nyctalopia onset, best corrected visual acuity (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) features. There was no statistical difference in the median age at onset (30 and 18 years; Mann-Whitney U test, p = 0.13); the mean age when 50% of the patients reached legal blindness (≥1.0 log MAR) based on visual acuity (64 years for both groups; log-rank, p = 0.3); the risk of developing advanced retinal degeneration (patch or atrophy) with age (multiple logistic regression, p = 0.8); or the frequency of cystoid macular edema (31% vs. 26%, Fisher's exact test, p = 0.4). ADGRV1 and USH2A retinopathy were indistinguishable in all major functional and structural characteristics, suggesting that the loss of function of the corresponding proteins produces similar effects in the retina. The results are important for counseling ADGRV1 patients, who represent the minor patient subgroup.

To investigate the structure-function correlation analysed by full-field electroretinography (ffERG) and optical coherence tomography (OCT) in typical and pericentral subtypes of retinitis pigmentosa (RP). A retrospective, cross-sectional, observational study of right eyes was conducted. The primary analysis used ffERG data to compare the RP subtypes. The subgroup analysis was used to correlate the structure, analysed by OCT, and function, determined by ffERG. Linear regressions explored the relationship between best-corrected visual acuity (BCVA) and multiple parameters. A total of 188 eyes were included. Amplitudes of responses of rod, rod-cone, cone, and 30 Hz flicker of typical type were lower than those of pericentral and other types. In the subgroup analysis, 41 and 21 eyes of the typical and pericentral types were studied, respectively. The correlation between the estimated preserved photoreceptor area and all ffERG amplitude parameters were significant in the typical type, but not in pericentral type. Old age, decreased intact ellipsoid zone length, typical type, and thin central retinal thickness were negatively correlated with BCVA. Typical type RP developed more extensive degeneration and poorer BCVA compared to others. Strong structure-function correlation was found in typical type while not in pericentral type. OCT may be a useful tool for monitoring RP status in typical type, providing useful parameters for the prediction of BCVA., (© 2021. The Author(s).)

The purpose of this study was to detect the presence of retinitis pigmentosa (RP) based on color fundus photographs using a deep learning model. A total of 1670 color fundus photographs from the Taiwan inherited retinal degeneration project and National Taiwan University Hospital were acquired and preprocessed. The fundus photographs were labeled RP or normal and divided into training and validation datasets (n = 1284) and a test dataset (n = 386). Three transfer learning models based on pre-trained Inception V3, Inception Resnet V2, and Xception deep learning architectures, respectively, were developed to classify the presence of RP on fundus images. The model sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were compared. The results from the best transfer learning model were compared with the reading results of two general ophthalmologists, one retinal specialist, and one specialist in retina and inherited retinal degenerations. A total of 935 RP and 324 normal images were used to train the models. The test dataset consisted of 193 RP and 193 normal images. Among the three transfer learning models evaluated, the Xception model had the best performance, achieving an AUROC of 96.74%. Gradient-weighted class activation mapping indicated that the contrast between the periphery and the macula on fundus photographs was an important feature in detecting RP. False-positive results were mostly obtained in cases of high myopia with highly tessellated retina, and false-negative results were mostly obtained in cases of unclear media, such as cataract, that led to a decrease in the contrast between the peripheral retina and the macula. Our model demonstrated the highest accuracy of 96.00%, which was comparable with the average results of 81.50%, of the other four ophthalmologists. Moreover, the accuracy was obtained at the same level of sensitivity (95.71%), as compared to an inherited retinal disease specialist. RP is an important disease, but its early and precise diagnosis is challenging. We developed and evaluated a transfer-learning-based model to detect RP from color fundus photographs. The results of this study validate the utility of deep learning in automating the identification of RP from fundus photographs., (© 2021. Society for Imaging Informatics in Medicine.)

Purpose: We developed and phenotyped a pigmented knockout rat model for lecithin retinol acyltransferase (LRAT) using CRISPR/Cas9. The introduced mutation (c.12delA) is based on a patient group harboring a homologous homozygous frameshift mutation in the LRAT gene (c.12delC), causing a dysfunctional visual (retinoid) cycle., Methods: The introduced mutation was confirmed by DNA and RNA sequencing. The expression of Lrat was determined on both the RNA and protein level in wildtype and knockout animals using RT-PCR and immunohistochemistry. The retinal structure and function, as well as the visual behavior of the Lrat -/- and control rats, were characterized using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG) and vision-based behavioral assays., Results: Wildtype animals had high Lrat mRNA expression in multiple tissues, including the eye and liver. In contrast, hardly any expression was detected in Lrat -/- animals. LRAT protein was abundantly present in wildtype animals and absent in Lrat -/- animals. Lrat -/- animals showed progressively reduced ERG potentials compared to wildtype controls from two weeks of age onwards. Vison-based behavioral assays confirmed reduced vision. Structural abnormalities, such as overall retinal thinning, were observed in Lrat -/- animals. The retinal thickness in knockout rats was decreased to roughly 80% by four months of age. No functional or structural differences were observed between wildtype and heterozygote animals., Conclusions: Our Lrat -/- rat is a new animal model for retinal dystrophy, especially for the LRAT -subtype of early-onset retinal dystrophies. This model has advantages over the existing mouse models and the RCS rat strain and can be used for translational studies of retinal dystrophies.

Background: Bardet-Biedl syndrome is an autosomal recessive disease characterized by rod-cone dystrophy, postaxial polydactyly, kidney defects, obesity, mental retardation and hypogonadism. Here, we report different genotypes in two Bardet-Biedl syndrome affected sisters with a different clinical phenotype regarding severity., Materials and Methods: The proband of the family was examined by Next Generation Sequencing (NGS) using clinical exome and filtering by syndromic and non-syndromic genes associated with retinal dystrophies., Results: Targeted NGS revealed two novel variants in the MKKS and CEP290 genes in homozygosis state in the proband. Segregation analysis revealed the presence of the same MKKS homozygous variant in her younger affected sister but not the CEP290 variant. Both sisters presented different clinical manifestation, at different ages, with a more severe renal and retinal defect in the case of the sister carrying mutations in both genes. Another unaffected sister showed only homozygosity for the CEP290 variant, thus supporting the non-pathogenic role of this mutation in BBS phenotype., Conclusions: In this study, NGS proved to be a powerful and efficient sequencing method to identify causal variants in different genes. However, it remarks the importance of the segregation analysis and clinical information to establish the pathogenicity of new variants. The two affected sisters present different genotypes and clinical manifestation, suggesting that the novel CEP290 variant could be acting as a modifier, making the phenotype more severe in the sister homozygote for MKKS and CEP290 genes. On the other hand, the difference in the age of both sisters highlight the important role of monitoring disease progression also to confirm the modifier role of genetic variants., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124&#95;128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.

Background : Syndromic ciliopathies have been variably linked to different retinal dystrophies. However, to date, few reports have characterized by means of multimodal imaging the retinal degeneration occurring in Mainzer-Saldino syndrome (MSS). Methods : Two siblings with history of kidney disease and other systemic abnormalities presented at our eye clinic in October 2017 complaining of night blindness and visual loss. They underwent a complete ophthalmologic examination including visual acuity (VA) assessment, optical coherence tomography (OCT) and blue-light autofluorescence (BAF). A screen for inherited retinal dystrophies was performed in this occasion. Results : At baseline, the youngest sister had slightly worse VA (20/30 vs. 20/20-25 Snellen equivalents). On fundoscopy, both siblings had severe thinning of the peripheral retina, attenuation of retinal vessels and widespread accumulation of pigmented deposits. Significant outer retinal atrophy with apparent foveal sparing was appreciable on OCT.During the 3 years of follow-up, vision remained overall stable in both patients whereas minimal progression of outer retinal atrophy was observed by means of OCT. Genetic analysis revealed compound heterozygosity in the IFT172 gene. Based on these findings, a diagnosis of retinitis pigmentosa (RP) associated with MSS was formulated. Conclusions : Our report describes the cases of two siblings affected by retinitis pigmentosa associated with MSS. Although both carrying the same mutations and a severe RP phenotype, the youngest sister had slightly more advanced retinal degeneration highlighting the remarkable variability related to the IFT172 retinopathy.

Ciliopathies are a broad range of inherited developmental and degenerative diseases associated with structural or functional defects in motile or primary non-motile cilia. There are around 200 known ciliopathy disease genes and whilst genetic testing can provide an accurate diagnosis, 24-60% of ciliopathy patients who undergo genetic testing do not receive a genetic diagnosis. This is partly because following current guidelines from the American College of Medical Genetics and the Association for Molecular Pathology, it is difficult to provide a confident clinical diagnosis of disease caused by missense or non-coding variants, which account for more than one-third of cases of disease. Mutations in PRPF31 are the second most common cause of the degenerative retinal ciliopathy autosomal dominant retinitis pigmentosa. Here, we present a high-throughput high-content imaging assay providing quantitative measure of effect of missense variants in PRPF31 which meets the recently published criteria for a baseline standard in vitro test for clinical variant interpretation. This assay utilizes a new PRPF31 +/- human retinal cell line generated using CRISPR gene editing to provide a stable cell line with significantly fewer cilia in which novel missense variants are expressed and characterised. We show that high-content imaging of cells expressing missense variants in a ciliopathy gene on a null background can allow characterisation of variants according to the cilia phenotype. We hope that this will be a useful tool for clinical characterisation of PRPF31 variants of uncertain significance, and can be extended to variant classification in other ciliopathies.

Purpose: Heterozygous mutations in the gene PRPF31 , encoding a pre-mRNA splicing factor, cause autosomal dominant retinitis pigmentosa (adRP) with reduced penetrance. At the molecular level, pathogenicity results from haploinsufficiency, as the largest majority of such mutations trigger nonsense-mediated mRNA decay or involve large deletions of coding exons. We investigated genetically two families with a history of adRP, one of whom showed incomplete penetrance., Methods: All patients underwent thorough ophthalmological examination, including electroretinography (ERG) and Goldmann perimetry. Array-based comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) were used to map heterozygous deletions, while real-time PCR on genomic DNA and long-range PCR allowed resolving the mutations at the base-pair level. PRPF31 transcripts were quantified with real-time PCR on patient-derived lymphoblastoid cell lines., Results: We identified two independent deletions affecting the promoter and the 5' untranslated region (UTR) of PRPF31 but leaving its coding sequence completely unaltered. Analysis of PRPF31 mRNA from lymphoblastoid cell lines from one of these families showed reduced levels of expression in patients versus controls, probably due to the heterozygous ablation of its promoter sequences., Conclusions: In addition to reporting the identification of two novel noncoding deletions in PRPF31 , this study provides strong additional evidence that mRNA-mediated haploinsufficiency is the primary cause of pathogenesis for PRPF31 -linked adRP., (Copyright © 2021 Molecular Vision.)

Purpose: The primary aim of our study was to evaluate retinal microvascular anomalies recorded with optical coherence tomography angiography (OCTA) and the retinal metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). The secondary aim of the study was to link the presence of macular edema to microvascular and metabolic parameters in RP., Methods: OCTA and RO were performed on 94 eyes: 64 eyes diagnosed with RP with (ME-RP) and without (no-ME-RP) macular edema were compared with 30 control eyes. Study end points were as follows: mean superficial (FAZ-S) and deep foveal avascular zone (FAZ-D) determined by OCTA. In addition, we evaluated the mean arterial (A-SO 2 ; %), venular (V-SO 2 ; %) oxygen saturation, their difference (A-V SO 2 ; %), as well as the corresponding mean diameter of the retinal arterioles (D-A; μm) and venules (D-V; μm)., Results: RP patients differed from controls by enlarged FAZ-S and FAZ-D (p ≤ 0.001), attenuated retinal vessels (p ≤ 0.001), and increased retinal vessel oxygen saturation (p ≤ 0.010). Subgroup analyses within RP patients revealed more pronounced alterations of microvascular parameters and metabolic function in the presence of macular edema. In the no-ME-RP subgroup, significant interactions were present between FAZ-S, A-SO 2 , and V-SO 2 , whereas in the ME-RP subgroup, we found significant correlations between FAZ-D and D-A., Conclusion: A combined microvascular structure-metabolic function approach enhances our understanding of inherited retinal diseases. The presence of macular edema in RP seems to be a result of more altered microvascular-metabolic function. Macular edema should thus be taken into consideration when evaluating microvascular and/or metabolic changes in RP.

(1) Background: The aim of our study was to investigate the relationship between retinal metabolic alterations (retinal vessel oximetry, RO) and structural findings (retinal vessel diameter, central retinal thickness and retinal nerve fiber layer thickness, RNFL) in patients with inherited retinal diseases (IRDs). (2) Methods: A total of 181 eyes of 92 subjects were examined: 121 eyes of 62 patients with IRDs were compared to 60 eyes of 30 healthy age-matched controls. The retinal vessel oximetry was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A-SO 2 ; %) and venules (V-SO 2 ; %) were measured and their difference (A-V SO 2 ; %) was calculated. Additionally, retinal vessel diameters of the corresponding arterioles (D-A; µm) and venules (D-V; µm) were determined. The peripapillary central retinal thickness and the RNFL thickness were measured using spectral domain optical coherence tomography (SD-OCT) (Carl Zeiss Meditec, Dublin, CA, USA). Moreover, we calculated the mean central retinal oxygen exposure (cO 2 -E; %/µm) and the mean peripapillary oxygen exposure (pO 2 -E; %/µm) per micron of central retinal thickness and nerve fiber layer thickness by dividing the mean central retinal thickness (CRT) and the RNFL thickness with the mean A-V SO 2 . (3) Results: Rod-cone dystrophy patients had the highest V-SO 2 and A-SO 2 , the lowest A-V SO 2 , the narrowest D-A and D-V and the thickest RNFL, when compared not only to controls ( p ≤ 0.040), but also to patients with other IRDs. Furthermore, in rod-cone dystrophies the cO 2 -E and the pO 2 -E were higher in comparison to controls and to patients with other IRDs ( p ≤ 0.005). Cone-rod dystrophy patients had the lowest cO 2 -E compared to controls and patients with other IRDs ( p ≤ 0.035). Evaluated in central zones, the cO 2 -E was significantly different when comparing cone-rod dystrophy (CRD) against rod-cone dystrophy (RCD) patients in all zones ( p < 0.001), whereas compared with controls and patients with inherited macular dystrophy this was observed only in zones 1 and 2 ( p ≤ 0.018). The oxygen exposure was also the highest in the RCD group for both the nasal and the temporal peripapillary area, among all the evaluated groups ( p ≤ 0.025). (4) Conclusions: The presented metabolic-structural approach enhances our understanding of inherited photoreceptor degenerations. Clearly demonstrated through the O 2 -E comparisons, the central and the peripapillary retina in rod-cone dystrophy eyes consume less oxygen than the control-eyes and eyes with other IRDs. Rod-cone dystrophy eyes seem to be proportionally more exposed to oxygen, the later presumably leading to more pronounced oxidative damage-related remodeling.

Thirty-eight patients from 37 families with retinitis pigmentosa (RP) underwent macular 6 × 6-mm swept-source optical coherence tomography angiography (SS-OCTA) and 30° near-infrared fundus autofluorescence (NIR-FAF) acquisitions in one eye. Superficial vascular complex (SVC), deep capillary complex (DCC) and choriocapillaris (CC) angiograms were registered with NIR-FAF acquisitions to comparatively assess subjects with and without central area of preserved NIR-FAF (APA). On the subset of patients showing an APA, the vessel densities for SVC and DCC and flow deficits for CC were assessed in three directions (superior, inferior and temporal) from the fovea and compared to healthy 1:1 age-matched controls. Nine patients with no APA had evidence of severe central OCTA alterations at all levels, especially in the DCC. In the other 29 subjects presenting APA, all OCTA parameters were similar to healthy eyes within the APA, where the retina preserves its structural integrity. Outside the APA, both the DCC and CC were significantly reduced in all directions. These alterations are probably related to the outer retinal atrophy outside the APA. Comparing OCTA to other imaging modalities is helpful to determine the potential interest of OCTA findings as an outcome measure for disease status and progression.

Objective: The purpose of this study is to explore the underlying functional network brain activity changes of patients in middle-aged with retinitis pigmentosa (RP) and the relationships with clinical features such as depression scale and visual functioning using voxel-wise degree centrality (DC) method., Methods: We included 16 patients with RP (11 men, 5 women) and 16 healthy controls (HCs; 11 men, 5 women). Participants were matched in terms of age, weight, gender and handedness (age and weight between the two groups were compared using independent sample t-tests, gender and handedness were compared using chi-square test). We use the voxel-wise DC method to assess spontaneous brain activity. Receiver operating characteristic (ROC) curve analysis was performed to distinguish between RP patients and HCs. Correlation analysis was used to examine the relationships between mean DC values in various brain regions and clinical features (such as depression scale and visual functioning) in RP patients., Results: Compared with HCs, the DC values of patients with RP were reduced in the right medial frontal gyrus, bilateral cuneus, bilateral precuneus, and bilateral superior frontal gyrus, and increased in the right cerebellum posterior lobe, left inferior temporal gyrus, and right fusiform gyrus. The mean DC values in the bilateral cuneus negatively correlated with the depression scale, and those in the bilateral precuneus positively correlated with the Visual Functioning Questionnaire-25., Conclusions: Middle-aged patients with RP exhibit abnormal brain network activity in various brain regions, and this may underlie the pathological mechanism of RP., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Mutations in the splicing factor pre-messenger RNA processing factor 31 ( PRPF31 ) gene cause autosomal dominant retinitis pigmentosa 11 (RP11) through a haplo-insufficiency mechanism. We describe the phenotype and progression of microperimetry and autofluorescence endpoints in an Indigenous Australian RP11 family., Patients and Methods: Ophthalmic examination, optical coherence tomography, fundus autofluorescence and microperimetry were performed at baseline and every 6-12 months. Baseline and annual change in best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS) and number of scotoma loci, residual ellipsoid zone (EZ) span and hyperautofluorescent ring (HAR) area were reported. Next-generation and Sanger sequencing were performed in available members., Results: 12 affected members from three generations were examined. Mean (SD, range) age at onset of symptoms was 11 (4.5, 4-19) years. MS declined steadily from the third decade and EZ span and HAR area declined rapidly during the second decade. Serial microperimetry showed negligible change in MS over 2-3 years. However, mean EZ span, near-infrared and short-wavelength HAR area reduction was 203 (6.4%) µm/year, 1.8 (8.7%) mm 2 /year and 1.1 (8.6%) mm 2 /year, respectively. Genetic testing was performed on 11 affected and 10 asymptomatic members and PRPF31 c.1205 C > A (p.Ser402Ter) mutation was detected in all affected and two asymptomatic members (non-penetrant carriers)., Conclusions: Our findings suggest that in the studied cohort, the optimal window for therapeutic intervention is the second decade of life and residual EZ span and HAR area can be considered as efficacy outcome measures. Further studies on larger samples with different PRPF31  mutations and longer follow-up duration are recommended.

Objective: The current methods used to assess visual function in blind retinitis pigmentosa (RP) patients are mostly subjective. We aimed to identify effective, objective methods., Methods: We enrolled patients diagnosed with blindness associated with RP; we finally selected 26 patients (51 eyes) with a visual field radius less than 10 degrees and divided them into the following 4 groups by best-corrected visual acuity (BCVA): group 1, no light perception (NLP, 4 eyes); group 2, light perception (LP, 12 eyes); group 3, hand movement or finger counting (faint form perception, FFP, 22 eyes); and group 4, BCVA from 0.1 to 0.8 (form perception, FP, 13 eyes). All patients underwent optometry, optical coherence tomography (OCT), color fundus photography, fundus autofluorescence (FAF), full field electroretinography (ffERG), pattern electroretinography (PERG), multifocal electroretinography (mf-ERG), pattern visual evoked potential (PVEP), flash visual evoked potential (FVEP), and pupillary light response (PLR) assessments. Five patients in groups 1, 2, and 3 (1, 2, and 2 subjects, respectively) underwent functional magnetic resonance imaging (fMRI) scans and were compared with five healthy subjects., Results: The outer plexiform layer was thinner in group 1, and the outer nuclear layer was thinner in groups 1 and 2. The ffERG, PERG, and mf-ERG findings were unrecordable in all four groups. The P2 amplitude of the FVEP was significantly lower in groups 1 and 2, while the P100 amplitude of the PVEP was higher in groups 2, 3 and 4 than in group 1. After white- and blue-light stimuli, the PLR thresholds in the patients without form perception were significantly higher. The threshold of the PLR stimulated by blue and white light was negatively correlated with the amplitudes of P2 and P100. Moreover, the fMRI findings showed that some RP patients have significant visual cortex activation in response to certain types of stimulation. However, statistical analysis was not performed because of the small number of cases., Conclusions: OCT, VEP, PLR and fMRI assessments can evaluate residual visual pathway function in blind RP patients., Significance: Our study may have clinical significance for the potential prediction of RP patient prognoses and the effects after clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: Progressive inherited retinal dystrophies, characterized by degeneration of rod photoreceptors and then cone photoreceptors, are known as retinitis pigmentosa (RP), for which 89 genes have been identified. Today, only five Moroccan families with RP with a genetic diagnosis have been reported, justifying our investment in providing further clinical and genetic investigations of families with RP in Morocco., Methods: The clinical diagnosis based on a combination of a history of night blindness, abnormal rod or rod-cone responses in electroretinography (ERG), and constricted visual field or difficulty perceiving side objects identified three Moroccan families with an RP phenotype. Probands of these families underwent whole exome sequencing (WES), and candidate variants were evaluated for their segregation within family members., Results: All patients had a history of night blindness and unrecordable rod and cone ERG traces. In addition, one patient had cystoid macular edema, and another had discrete autofluorescence abnormalities, in addition to ellipsoid zone disorganization and narrowed retinal vessels. WES sequencing revealed heterozygous compound mutations in CRB1 :c.1690G>T//c.1913C>T and in ABCA4 :c.5908C>T//c.6148G>C and a homozygous PDE6B splice mutation c.1920+2T>C., Conclusions: We provide the first description of Moroccan patients with the RP phenotype harboring pathogenic mutations in the CRB1 and ABCA4 genes and the second description of an individual with RP with a PDE6B mutation, associated with cystoid macular edema. These data contribute to expand the genetic diagnosis of RP phenotypes in Morocco., (Copyright © 2021 Molecular Vision.)

Purpose: To describe two methods of measuring Argus II array-retina distance and to correlate array-retina distance to electrode stimulation thresholds., Methods: This was a case series of eight patients implanted with the Argus II. Spectral domain-optical coherence tomography array-retina distance was measured by two methods and correlated to corresponding electrode thresholds: (1) array-retina distance at each array corner and the largest array-retina distance and (2) using manual optical coherence tomography segmentation, the average array-retina distance was determined for each group of four electrodes. Patients 1-5 and 6-8 were analyzed separately due to a different threshold programming software., Results: The Spearman's rank coefficient between array-retina distance and thresholds was -0.006 ( p  = 0.98) for patients 1-5, and 0.16 ( p  = 0.59) for patients 6-8 with the first method. The Spearman's rank coefficient was 0.25 ( p  < 0.001) for patients 1-5 and 0.36 ( p  < 0.001) for patients 6-8 with the second method., Conclusion: There is a positive correlation between array-retina distance and threshold measurements when measuring the entire array but not when using a faster measurement method of four corners and largest array-retina distance.

Purpose: The purpose of this study was to perform a detailed longitudinal phenotyping of X-linked retinitis pigmentosa (RP) caused by mutations in the RPGR gene during a long follow-up period., Methods: An Italian cohort of 48 male patients (from 31 unrelated families) with RPGR-associated RP was clinically assessed at a single center (mean follow-up = 6.5 years), including measurements of best-corrected visual acuity (BCVA), Goldmann visual field (GVF), optical coherence tomography (OCT), fundus autofluorescence (FAF), microperimetry, and full-field electroretinography (ERG)., Results: Patients (29.6 ± 15.2 years) showed a mean BCVA of 0.6 ± 0.7 logMAR, mostly with myopic refraction (79.2%). Thirty patients (62.5%) presented a typical RP fundus, while the remaining sine pigmento RP. Over the follow-up, BCVA significantly declined at a mean rate of 0.025 logMAR/year. Typical RP and high myopia were associated with a significantly faster decline of BCVA. Blindness was driven primarily by GVF loss. ERG responses with a rod-cone pattern of dysfunction were detectable in patients (50%) that were significantly younger and more frequently presented sine pigmento RP. Thirteen patients (27.1%) had macular abnormalities without cystoid macular edema. Patients (50%) with a perimacular hyper-FAF ring were significantly younger, had a higher BCVA and a better-preserved ellipsoid zone band than those with markedly decreased FAF. Patients harboring pathogenic variants in exons 1 to 14 showed a milder phenotype compared to those with ORF15 mutations., Conclusions: Our monocentric, longitudinal retrospective study revealed a spectrum disease progression in male patients with RPGR-associated RP. Slow disease progression correlated with sine pigmento RP, absence of high myopia, and mutations in RPGR exons 1 to 14.

We report a case of 19-year-old man with gradual diminution of vision in both eyes since childhood. His best-corrected visual acuity was 20/160, N16 in the right eye and 20/200, N16 in the left eye. Slit-lamp biomicroscopic examination revealed normal cornea, anterior segment, intraocular pressure and lens. Fundus of both eyes showed crowded optic disc with pigmentary changes. Ancillary tests were performed to aid in the diagnosis. A-scan ultrasound revealed short axial lengths with normal corneal diameter, anterior chamber depth and lens thickness. Optical coherence tomography of both eyes showed inner retinal layer folds. Electroretinogram of both eyes showed extinguished photopic as well as scoptopic responses. A diagnosis of posterior microphthalmos with pigmentary retinopathy was made. The patient was counselled regarding nature of the disease and the condition was managed with low vision aids., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

RPE65 isomerase, expressed in the retinal pigmented epithelium (RPE), is an enzymatic component of the retinoid cycle, converting all-trans retinyl ester into 11-cis retinol, and it is essential for vision, because it replenishes the photon capturing 11-cis retinal. To date, almost 200 loss-of-function mutations have been identified within the RPE65 gene causing inherited retinal dystrophies, most notably Leber congenital amaurosis (LCA) and autosomal recessive retinitis pigmentosa (arRP), which are both severe and early onset disease entities. We previously reported a mutation, D477G, co-segregating with the disease in a late-onset form of autosomal dominant RP (adRP) with choroidal involvement; uniquely, it is the only RPE65 variant to be described with a dominant component. Families or individuals with this variant have been encountered in five countries, and a number of subsequent studies have been reported in which the molecular biological and physiological properties of the variant have been studied in further detail, including observations of possible novel functions in addition to reduced RPE65 enzymatic activity. With regard to the latter, a human phase 1b proof-of-concept study has recently been reported in which aspects of remaining vision were improved for up to one year in four of five patients with advanced disease receiving a single one-week oral dose of 9-cis retinaldehyde, which is the first report showing efficacy and safety of an oral therapy for a dominant form of RP. Here, we review data accrued from published studies investigating molecular mechanisms of this unique variant and include hitherto unpublished material on the clinical spectrum of disease encountered in patients with the D477G variant, which, in many cases bears striking similarities to choroideremia.