Multifractal Analysis of Choroidal SDOCT Images in the Detection of Retinitis Pigmentosa.

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.

Quantitative microvascular analysis in different stages of retinitis pigmentosa using optical coherence tomography angiography.

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 mm2, 2.96 ± 0.86 mm, respectively) were larger than those in early (0.26 ± 0.11 mm2, P = 0.020; 2.19 ± 0.53 mm, P = 0.006, respectively) and moderate stage (0.28 ± 0.13 mm2, 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.

Evaluation of photoreceptor features in retinitis pigmentosa with cystoid macular edema by using an adaptive optics fundus camera.

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.

New insights in the multimodal imaging of retinitis pigmentosa.

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.

The suprachoroidal space in patients affected by retinitis pigmentosa.

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 ±â€¯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 ±â€¯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.

Evaluation of retina and choroid perfusion with optical coherence tomography angiography in patients with retinitis pigmentosa.

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.

Clinical Characteristics and Genetic Variants of a Large Cohort of Patients with Retinitis Pigmentosa Using Multimodal Imaging and Next Generation Sequencing.

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.

Microvascular quantitative metrics in retinitis pigmentosa using optical coherence tomography angiography.

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 ±â€¯3.79 vs 48.86 ±â€¯2.62, P < .0001; Nasal 40,52 ±â€¯4.30 vs 46,01 ±â€¯3.23, P = .0002; Inferior 42.76 ±â€¯5.26 vs 50.10 ±â€¯3.36, P < .0001; Temporal 40.42 ±â€¯4.46 vs 46.09 ±â€¯2.91, P = .0001) and in all but nasal sector in the SVP (Superior 39.86 ±â€¯4.46 vs 46.47 ±â€¯2.61, P < .0001; Nasal 40.35 ±â€¯4.56 vs 44.09 ±â€¯2.87, P = .0067; Inferior 40.74 ±â€¯4.61 vs 46.58 ±â€¯3.26, P = .0002; Temporal 39.98 ±â€¯5.07 vs 44.78 ±â€¯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.

Characterizing macular edema in retinitis pigmentosa through a combined structural and microvascular optical coherence tomography investigation.

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.

Fundus Photography Methodologies to Assess RP Patients.

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.

The Use of Optical Coherence Tomography in Evaluation of Retinitis Pigmentosa.

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.

Optical Coherence Tomography Angiography (OCTA) Findings in Retinitis Pigmentosa.

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.

Clinical presentation and macular morphology in retinitis pigmentosa patients.

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.

Résumé Contexte: La tomographie par cohérence optique (OCT) est une technologie d'imagerie non invasive fréquemment utilisée qui permet une visualisation détaillée de l'anatomie de la rétine. Elle est utilisée pour surveiller la progression de la maladie dans les yeux de la rétinite pigmentaire (RP), y compris la détection des changements dans l'épaisseur de la rétine. Objectif: Le but de l'étude était de déterminer la présentation clinique et la morphologie maculaire des yeux présentant une RP à l'aide de l'imagerie OCT. Méthodes: Une revue rétrospective des dossiers de cas et des scans OCT dans les yeux diagnostiqués de RP a été réalisée dans deux cliniques ophtalmologiques au Nigeria. Les données biographiques, la meilleure acuité visuelle corrigée de Snellen (MAVC), la pression intraoculaire (PIO), le rapport cup-sur-disc vertical (RCDV) et la présence de maculopathie ont été déterminés. Les données ont été analysées à l'aide d'IBM SPSS version 22.0 (IBM Corp. Armonk, NY, USA). Résultats: Cinquante-cinq yeux de 28 patients (18 hommes et 10 femmes), âgés en moyenne de 47,16 ± 15,56 ans (22­77 ans) ont été étudiés. Les 40 à 49 ans étaient la tranche d'âge la plus fréquente à 28,6 %. Une déficience visuelle sévère est survenue dans 22 % des yeux et une myopie dans 32 %. Vingt-neuf pour cent avaient subi une chirurgie de la cataracte ou avaient une cataracte importante. La PIO moyenne était de 11 mmHg et le RCDV moyen était de 0,46. À l'examen OCT, on retrouvait l'atrophie maculaire prédominante dans 74,5 % des yeux, la membrane épirétinienne (16,3 %), l'œdème maculaire cystoïde (7,3 %), l'adhérence vitréomaculaire (5,4 %) et la traction vitréomaculaire (1,8 %). Il n'y avait aucune association entre la morphologie maculaire, l'épaisseur maculaire et la MAVC (P = 0,155, P = 0,424). Conclusion: l'OCT fournit des informations sur la structure de la macula dans la RP. Environ 14,5% des yeux avaient une macula normale contre 85,5% avec maculopathie, confirmant ainsi que les yeux avec RP ont un taux de maculopathie plus élevé que les yeux sans RP. L'évaluation OCT d'un œil avec RP devrait être un bilan standard pour la détection précoce de maculopathie et la surveillance de la progression de la maladie. Mots-clés: Membrane épirétinienne, dystrophie rétinienne héréditaire, atrophie maculaire, œdème maculaire, tomographie par cohérence optique, rétinite pigmentaire.

Vessel density and choroidal vascularity index in patients with Bietti crystalline dystrophy and retinitis pigmentosa.

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.

Optical coherence tomography angiography in retinitis pigmentosa: A narrative review.

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.

Retinal pigment epithelium melanin imaging using polarization-sensitive optical coherence tomography for patients with retinitis pigmentosa.

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.

Quantitative and qualitative characterization of retinal dystrophies in canine models of inherited retinal diseases using spectral domain optical coherence tomography (SD-OCT).

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.

Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging.

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.

Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation.

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.