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Purpose To describe with multimodal imaging including the use of ultra-widefield optical coherence tomography (OCT) imaging a distinct phenotype of autosomal recessive nanophthalmos associated with a novel mutation of the MFRP gene (membrane-type frizzled-related protein). Methods Case report and review of the relevant literature. Patients Single patient followed by the Weill Cornell Medicine Department of Ophthalmology Retina and Glaucoma Services. Results A patient with a novel homozygous mutation in the MFRP gene (c.472C>T) presented with nanophthalmos, optic disc drusen, foveal hypoplasia, and extensive peripheral retinoschisis, which was revealed to be multilevel retinoschisis on ultra-wide field OCT. Unlike other reported cases, the findings associated with this novel mutation did not include foveoschisis nor clinically obvious retinitis pigmentosa. The patient underwent prophylactic peripheral laser iridotomy in both eyes. Conclusion Here we present a patient with nanophthalmos, optic disc drusen, and foveal hypoplasia associated with extensive peripheral retinoschisis imaged by ultra-widefield OCT, but not foveal retinoschisis or prominent retinitis pigmentosa. The findings may expand the clinical spectrum of MFRP-associated nanophthalmos.

To compare full-field stimulus (FST) threshold values to conventional functional and anatomical measures commonly used in clinical practice.Cross-sectional study.Patients with retinitis pigmentosa with nondetectable electroretinogram rod-mediated responses and light-adapted 3.0 cd·s·mForty-two eyes of 21 patients were included in the study. The mean FST thresholds were -22.5 ± 15.5 dB, -17.6 ± 11.5 dB, and -12.7 ± 6.0 dB for the blue, white, and red stimuli, respectively. The threshold values for the 3 FST stimuli were significantly correlated with selected functional and anatomical outcome measures. Specifically, they were strongly correlated with LA 3.0 flicker amplitude and EZ band length measured on optical coherence tomography. Using linear regression, blue and white stimulus values on FST were found to be predictive of EZ band length (RThe significant correlations between FST and other clinical outcome measures highlight its potential as an adjunct outcome measure.

Background and Objective: To characterize rod-pathway function across the visual field using 2-color dark-adapted perimetry (2cDAP) implemented with conventional Octopus 900 Pro perimeters. Patients and Methods: Eighteen visually normal individuals and two retinitis pigmentosa (RP) patients participated. Thresholds were measured under dark-adapted conditions at 15 locations along the horizontal meridian using short (450 nm) and long (610 nm) wavelength stimuli. Threshold differences between the two wavelengths were used to determine rod- vs cone-mediated function. Results: Among controls, peripheral and perifoveal thresholds for the short-wavelength stimulus were approximately 2 log units lower than for the long-wavelength stimulus. Foveal thresholds for the two wavelengths were similar. RP threshold profiles differed considerably from the controls, with normal foveal thresholds and high peripheral thresholds for both wavelengths. Conclusions: 2cDAP can be performed with an unmodified Octopus perimeter to evaluate rod function across the visual field and obtain information that is not available with standard automated perimetry. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:692–696.]

A 49-year-old woman was referred to the retina clinic with incidentally noted retinal pigmentation. She had long-standing poor left visual acuity (VA) due to a compressive optic neuropathy treated by surgery in childhood. She also had chronic angle closure glaucoma, treated with bilateral laser

Usher syndrome-associated retinitis pigmentosa (RP) causes progressive retinal degeneration, which has no cure. The pathomechanism of Usher type 1B (USH1B)-RP caused by MYO7A mutation remains elusive because of the lack of faithful animal models and limited knowledge of MYO7A function. Here, we analyzed 3D retinal organoids generated from USH1B patient-derived induced pluripotent stem cells. Increased differential gene expression occurred over time without excessive photoreceptor cell death in USH1B organoids compared with controls. Dysregulated genes were enriched first for mitochondrial functions and then proteasomal ubiquitin-dependent protein catabolic processes and RNA splicing. Single-cell RNA sequencing revealed MYO7A expression in rod photoreceptor and Müller glial cells corresponding to upregulation of stress responses in NRL

To investigate longitudinal changes in the retinal and choroidal microstructure of the macula in patients with retinitis pigmentosa (RP).Retrospective, observational cohort study.A total of 69 patients with RP and 69 age- and sex-matched controls who underwent optical coherence tomography (OCT) over a 4-year follow-up period were included. The severity of RP was classified into 3 stages according to the integrity of the inner segment ellipsoid zone. The retinal and choroidal layers were segmented manually from OCT images. The areas of retinal pigment epithelium (RPE) atrophy and choroidal vascular index (CVI) were also analyzed. Longitudinal changes in the OCT parameters were compared among the groups.Significant decreases (median [interquartile range]) in the thickness of the ganglion cell inner plexiform layer (GCIPL; -1.04 [-2.41 to -0.17]), outer nuclear layer (ONL; -1.44 [-1.86 to -0.28]), and inner segment ellipsoid (ISE; -0.74 [-1.33 to -0.49]) at the moderate stage and retinal nerve fiber layer (RNFL; -1.49 [-2.08 to -0.66]) and GCIPL (0.58 [-1.79 to 0.06]) at the advanced stage were observed. Choroidal thickness decreased significantly from -7.62 to -9.40 μm per year at all stages. RPE atrophy and CVI reduction were observed at the advanced stage. There was no change in the control group.ONL and GCIPL thicknesses decreased at the moderate and advanced stages of RP; RNFL thickness decreased only at the advanced stage; and choroidal thickness decreased continuously. In addition, RPE atrophy and CVI reduction were prominent at the advanced stage. These results indicate that there is a temporal variation in the damage of each retinal layer and the choroid in RP patients.

The Joubert syndrome (JS), Meckel syndrome (MKS), and nephronophthisis (NPH) ciliopathy spectrum could be the poster child for advances and challenges in Mendelian human genetics over the past half century. Progress in understanding these conditions illustrates many core concepts of human genetics. The JS phenotype alone is caused by pathogenic variants in more than 40 genes; remarkably, all of the associated proteins function in and around the primary cilium. Primary cilia are near-ubiquitous, microtubule-based organelles that play crucial roles in development and homeostasis. Protruding from the cell, these cellular antennae sense diverse signals and mediate Hedgehog and other critical signaling pathways. Ciliary dysfunction causes many human conditions termed ciliopathies, which range from multiple congenital malformations to adult-onset single-organ failure. Research on the genetics of the JS-MKS-NPH spectrum has spurred extensive functional work exploring the broadly important role of primary cilia in health and disease. This functional work promises to illuminate the mechanisms underlying JS-MKS-NPH in humans, identify therapeutic targets across genetic causes, and generate future precision treatments.

Retinitis pigmentosa (RP) constitutes a class of common inherited retinal dystrophies. Patients with RP and comorbid primary angle-closure glaucoma (PACG) have been described, but the relationship between the diseases remains unclear. This study investigated the clinical and genetic characteristics of Chinese patients with RP and comorbid PACG.Of 1356 patients with RP, we analyzed the genetic features of 39 RP patients with PACG using next-generation sequencing and reviewed their clinical characteristics.In total, 18 patients with acute PACG and 21 patients with chronic PACG were included in this study; their age at examination was 50.54 ± 12.99 years (range, 25.0-71.0 years), and their age at PACG onset was 46.04 ± 14.50 years (range, 24.9-68.0 years). Additionally, the mean lens thickness (LT) was 4.49 ± 0.44 μm, and the mean axial length (AL) was 22.63 ± 1.17 mm. Notably, the prevalence of PACG in patients with RP was 2.88%; this was higher than the prevalence in the general population. This could be explained by nanophthalmos, thickened lentis, ectopia lentis, or zonular insufficiency. Furthermore, patients with a shorter AL, a greater LT, iridociliary cysts, or nanophthalmos exhibited earlier development of PACG. Overall, 30 disease-causing variants spanning 17 genes were identified in 56.41% of the patients, andOur findings revealed that there is a strong association between RP and PACG. Furthermore, intraocular pressure (IOP) should be measured in patients with RP to protect them from the aggravated damage of an elevated IOP.

Retinitis pigmentosa (RP) is a genetically heterogeneous retinal dystrophy which results in progressive vision loss. There is scant literature on the experiences of genetic testing in patients with RP.Patients with a clinical diagnosis of RP who received genetic testing at the Wills Eye Ocular Genetics clinic between 2016 and 2020 were recruited. Telephone interviews were conducted using a semi-structured guide designed to elicit participant experiences with genetic testing. A thematic analysis was performed to describe patterns in participant responses.Twelve patients participated. Seven participants identified as female and five as male, with ages ranging from 22 to 70. Ten patients had positive genetic test results, while two had negative genetic testing. Reported motivations for genetic testing included qualification for clinical trials (58% of total participants), determination of etiology or usal gene (50%), reproductive concerns (50%), and prognostic outlook (50%). Most participants (75%) expressed satisfaction about their decision to pursue genetic testing. Participants with both positive and negative genetic testing reported persistent uncertainty regarding their prognosis for visual decline (50%). Genetic confirmation of disease leads to initiation of safety and vision-protecting health behaviors (42%).Patients with RP are generally satisfied with their testing experience, despite approaching testing with a wide range of motivations and expectations. Future research can leverage this methodology to identify targets for improvement in pre- and post-test education and counselling.

Glucose metabolism in the retina is carefully orchestrated, with glucose being delivered to photoreceptors from the choroidal circulation through the retinal pigmented epithelium (RPE). In photoreceptors, glucose is processed principally by aerobic glycolysis, from which the lactate byproduct is provided to the RPE and Müller glia for their energetic needs. In this study, we utilize a modified arrestin1 protein to enhance the glycolytic output of lactate from rod photoreceptors through disinhibition of enolase1 activity with the goal being to use this increased lactate production as a gene-agnostic approach to slowing retinal degeneration. Mouse arrestin1 with E362G/D363G amino acid substitutions (referred to as "ArrGG") was packaged into AAV and tested for safety and for efficacy in increasing retinal lactate production. Overexpression of ArrGG in C57BL/6J mice did not result in any detectable changes in either electroretinogram (ERG) function or photoreceptor survival as measured by outer nuclear layer (ONL) thickness. However, mouse retinas expressing ArrGG showed a ∼25% increase in the rate of lactate secretion. Therefore, AAV-ArrGG was delivered intravitreally to heterozygous P23H rhodopsin knockin mice (

Emerging treatments are being developed for inherited retinal diseases, requiring a clear understanding of natural progression and a database of potential participants for clinical trials. This article describes the rationale, study design and methodology of the Victorian Evolution of inherited retinal diseases NaTUral history REgistry (VENTURE), including data from the first 150 participants enrolled.VENTURE collects retrospective and prospective data from people with inherited retinal diseases. Following registration, participants are asked to attend a baseline examination using a standardised protocol to confirm their inherited retinal disease diagnosis. Examination procedures include (i) retinal function, using visual acuity and perimetry; (ii) retinal structure, using multimodal imaging and (iii) patient-reported outcomes. Participants' molecular diagnoses are obtained from their clinical records or through targeted-panel genetic testing by an independent laboratory. Phenotype and genotype data are used to enrol participants into disease-specific longitudinal cohort sub-studies.From 7 July 2020 to 30 December 2021, VENTURE enrolled 150 registrants (138 families) and most (63%) have a rod-cone dystrophy phenotype. From 93 participants who have received a probable molecular diagnosis, the most common affected genes are RPGR (13% of all registrants), USH2A (10%), CYP4V2 (7%), ABCA4 (5%), and CHM (5%). Most participants have early to moderate vision impairment, with over half (55%) having visual acuities of better than 6/60 (20/200) at registration.The VENTURE study will complement existing patient registries and help drive inherited retinal disease research in Australia, facilitating access to research opportunities for individuals with inherited retinal diseases.

Retinitis pigmentosa is a retinal disorder leading to a progressive visual field loss and eventually to complete blindness, but an early diagnosis could delay its progression through specific therapies. Retinitis pigmentosa is characterized by typical pigment signs that accumulate in the different regions of the retina. Pigment signs could be detected by a low-cost diagnosis tool, analyzing visual fundus retinal images and applying segmentation algorithms to annotate the pigments, so that, in a telemedicine scenario, the segmented images could be forwarded to an ophthalmologist for a rapid diagnosis.Deep learning approaches might be appropriate for this problem, but they have rarely been used to address it. However, pigment segmentation is a challenging task due to image resolution, small size of pigments and their proximity with blood vessels with which they share similar colors, and inter-patient widely changing image features. Very recently, transformer architectures, based on the self-attention paradigm, have emerged in the deep learning community as a powerful yet not completely explored tool to learn features directly from the data. Nonetheless, they could not be directly exploited on small datasets, as they require a very large amount of data to learn meaningful features. To overcome the need for large training datasets, but also to reduce the high computation effort, hybrid architectures have been proposed, with the aim to combine the long-range relationship detection of transformers with the invariance and short-range detection properties of classical deep learning architectures. Here, we investigate the performances of the Group Transformer U-Net, a hybrid approach for pigment segmentation on fundus images. This hybrid architecture modifies the classical U-Net structure introducing bottleneck multihead self-attention blocks between convolutional layers in both the contracting and expanding paths of the network. We compare the results obtained with this approach with the ones of the standard U-Net, and we describe how these results are affected when using different loss functions for the learning process, or strategies to address class imbalance.

Clinical phenotypes of a patient with a deletion of the entire

To analyze the genotype-phenotype correlation in patients with retinitis pigmentosa (RP) caused by mutations in the FAM161A, DHDDS, or MAK genes using ultra-widefield fundus autofluorescence (UWF-FAF) imaging.Retrospective case series of patients with autosomal recessive RP (ARRP) with confirmed causative genetic mutations and available UWF-FAF imaging data. The UWF-FAF data were graded in a blinded fashion using the following criteria: the pattern of macular abnormalities on FAF, the presence or absence of horizontal linear hyperautofluorescence, the extent of decreased autofluorescence (DAF), the shape of DAF, and the presence of hyperautofluorescence at the optic disk.A total of 43 patients (mean age of 47 ± 16 years, ranging from 17 to 79 years) with ARRP (86 eyes) were included in our analysis. Genotyping data revealed biallelic mutations in the FAM161A, DHDDS, and MAK genes in 20, 12, and 11 patients, respectively. We found significant differences between the three groups with respect to the pattern of macular abnormalities on FAF (p = 0.001), DAF configuration (p = 0.007), and extent of DAF (p = 0.037). The largest difference between groups was found for macular abnormalities on FAF, with DHDDS patients differing significantly from the MAK and FAM161A groups (p = 0.001). Specifically, DHDDS patients had a more abnormal macular FAF pattern and more widespread decrease in peripheral autofluorescence. No other parameters differed significantly between the three groups.Patients with ARRP can present with specific UWF-FAF patterns based on the underlying causative gene. Future studies are warranted in order to expand this analysis to include additional genes, mutations, and patients as well as assessment of disease progression by following patients over longer periods of time.

Resumen: Introducción. El síndrome de Usher es una alteración genética caracterizada por la asociación de retinitis pigmentaria y sordera. Sin embargo, hay casos con familias en las cuales, a pesar de presentarse dicha asociación, no se puede diagnosticar un síndrome de Usher ni ninguno otro. Objetivo. Reevaluar fenotípicamente a 103 familias con diagnóstico previo de posible síndrome de Usher o retinitis pigmentaria asociada con sordera. Materiales y métodos. Se revisaron las historias clínicas de 103 familias con un posible diagnóstico clínico de síndrome de Usher o retinitis pigmentaria asociada con sordera. Se seleccionaron las familias cuyo diagnóstico clínico no correspondía a un síndrome de Usher típico. Los afectados fueron valorados oftalmológica y audiológicamente. Se analizaron variables demográficas y clínicas. Resultados. Se reevaluaron 14 familias cuyo diagnóstico clínico no correspondía al de síndrome de Usher. De las familias con diagnóstico inicial de síndrome de Usher típico, el 13,6 % recibieron uno posterior de “retinitis pigmentaria asociada con sordera” de “otro síntoma ocular asociado con hipoacusia’,’ o en forma aislada en una misma familia, de “retinitis pigmentaria” o “hipoacusia’.’ Conclusiones. Es fundamental el estudio familiar en los casos en que la clínica no concuerda con el diagnóstico de síndrome de Usher típico. En los pacientes con retinitis pigmentaria asociada con sordera, el diagnóstico clínico acertado permite enfocar los análisis moleculares y, así, establecer un diagnóstico diferencial. Es necesario elaborar guías de nomenclatura en los casos con estos hallazgos atípicos para orientar a médicos e investigadores en cuanto a su correcto manejo. Abstract: Introduction: There are several syndromes that associate retinitis pigmentosa with deafness or hearing loss. The most frequent is Usher syndrome, a genetic disorder of autosomal recessive inheritance, which, in some cases, is accompanied by vestibular dysfunction. However, there are cases of families that despite having retinitis pigmentosa associated with deafness, cannot be classified as Usher or other syndromes due to additional findings. Objective: To reassess the phenotypes of 103 families previously diagnosed as possible Usher syndrome and/or retinitis pigmentosa associated with deafness. Materials and methods: We conducted a descriptive and retrospective study by reviewing the medical records of 103 families with a probable clinical diagnosis of Usher syndrome and/or retinitis pigmentosa associated with deafness. Families whose clinical diagnosis did not correspond to the typical Usher syndrome were selected and evaluated ophthalmologically and audiologically. Demographic and clinical variables were analyzed. Results: We selected and then reevaluated 14 families and 55 individuals as they did not correspond to a clinical diagnosis of Usher syndrome; 13.6% of the families initially considered to have typical Usher syndrome were later diagnosed with retinitis pigmentosa associated with deafness, another ocular symptom associated with hearing loss, retinitis pigmentosa, or isolated hearing loss in the same family. Conclusions: Family studies are essential in cases where the symptoms do not match the typical Usher’ syndrome. In the cases of retinitis pigmentosa associated with deafness, a correct clinical diagnosis allows for focusing on the molecular analyses to establish a differential diagnosis. The need for nomenclature guidelines on these atypical findings is relevant to aid physicians and researchers in the best approach to these cases.

To describe clinical and genetic characteristics in a series of Chinese patients with non-syndromic retinitis pigmentosa, a total of 20 unrelated Chinese pedigrees with non-syndromic retinitis pigmentosa were evaluated. Complete ophthalmic examinations data including the Humphrey visual field, spectral domain-optical coherence tomography, full-field electroretinography, and fundus fluorescence were collected and analyzed. Targeted exome sequencing was utilized to investigate variations in 260 known genes of inherited retinal disease, including the 90 known causative retinitis pigmentosa genes. We initially identified the potential candidate variants in the pedigrees, then validated the variants using the Sanger sequencing and performed segregation analysis to verify that the variants constituted disease-causing mutations in these pedigrees. We detected three novel (likely) pathogenic and eight previously reported (likely) pathogenic variations in nine genes reported to be related to non-syndromic retinitis pigmentosa in nine of the pedigrees. We report clinical characteristics of Chinese patients with retinitis pigmentosa and novel mutations responsible for non-syndromic retinitis pigmentosa in Chinese pedigrees, expanding the number of gene mutations associated with this disorder and clarifying its genetic basis in the Chinese population. These data will help with rapid and efficient molecular diagnosis and the study of targeted treatment for retinitis pigmentosa in this population.

Background. Leber congenital amaurosis (LCA) is a monogenic, but genetically heterogenous disease, and at least 27 genes are implicated. This case report is aimed at providing evidence to link the novel variant RPE65 c.393T>A, p.(Asn131Lys), variant of uncertain significance (VUS), to clinical phenotype and to set the ground for objective assignment of pathogenicity confidence. Case Presentation. A case report of a female patient with LCA who manifested with nystagmus, night blindness, profound visual deficiency, and peripheral involvement of the retina consistent with RPE65 dystrophy. A thorough clinical examination, diagnostic evaluation, and genetic testing were performed. The patient was a compound heterozygote in trans form: RPE65 c.304G>T, p.(Glu102 ∗ ) pathogenic, and RPE65 c.393T>A, p.(Asn131Lys), VUS. The latter variant is absent in healthy controls and is considered harmful on in silico prediction. Conclusions. We conclude that RPE65 c.393T>A, p.(Asn131Lys) contributed to the pathologic phenotype, demonstrating its significance clearly in the case presented, and should be reclassified according to the criteria of evidence as likely pathogenic. This being the case, patients with this specific variant are likely candidates for genetic treatment.

The aim of our study was to evaluate retinal function with white light dark-adapted full-field sensitivity threshold (FST) and find possible correlations with metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP).In this prospective observational study (BASEC 2020-00,122), FST and RO measurements were performed on 66 RP eyes (33 subjects, 12♀ 21♂) aged between 18 and 80 years (mean 43.2 years); all eyes were graded for disease severity. Main outcome parameters were white FST thresholds using the Diagnosys Espion system with the ColorDomeTM LED full-field stimulator (Diagnosys LLC, Lowell, MA) as well as the main RO parameters: the mean arterial (A-SONeither the oxygen saturation parameters (p 0.21) nor the D-A and D-V (p 0.13) showed significant correlations with the FST. However, when compared systematically with the visual field (VF) areas of the different isopters, RO parameters V-SOIn contrast to standardized VF parameters, white dark-adapted FST appears not to correlate with retinal oxygen metabolic function measured with RO in patients with RP, suggesting that the two examinations may capture unrelated aspects of the retinal pathological process. However, RO showed a significant association with standardized VF testing parameters and may, therefore, offer an alternative outcome measure for interventional trials.

Contains fulltext : 251572.pdf (Publisher’s version ) (Closed access) We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose-dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue-specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.

To evaluate the clinical and genetic spectrum of inherited retinal diseases (IRDs) in a Kuwaiti tribe.Forty four patients with IRDs from 28 nuclear families from the tribe, were evaluated for presenting symptoms, visual acuity, fundus examination, OCT, microperimetry, full-field (ff), and multifocal electroretinography (mERG) and genotyping.Seventeen patients were diagnosed with autosomal recessive retinitis pigmentosa (arRP) associated withThis study represents a typical tribe from the Middle East with high rate of consanguinity for many generations that harbors multiple mutated genes associated with IRD. It demonstrates the predominant phenotype and its variability in retinal disorders caused by identical mutations and illustrates the nuances in the clinical presentation and disease progression of patients with pathogenic mutations in more than one gene.

Contains fulltext : 282683.pdf (Publisher’s version ) (Open Access) Retinitis pigmentosa (RP) is a genetically heterogeneous form of inherited retinal disease that leads to progressive visual impairment. One genetic subtype of RP, RP54, has been linked to mutations in PCARE (photoreceptor cilium actin regulator). We have recently shown that PCARE recruits WASF3 to the tip of a primary cilium, and thereby activates an Arp2/3 complex which results in the remodeling of actin filaments that drives the expansion of the ciliary tip membrane. On the basis of these findings, and the lack of proper photoreceptor development in mice lacking Pcare, we postulated that PCARE plays an important role in photoreceptor outer segment disk formation. In this study, we aimed to decipher the relationship between predicted structural and function amino acid motifs within PCARE and its function. Our results show that PCARE contains a predicted helical coiled coil domain together with evolutionary conserved binding sites for photoreceptor kinase MAK (type RP62), as well as EVH1 domain-binding linear motifs. Upon deletion of the helical domain, PCARE failed to localize to the cilia. Furthermore, upon deletion of the EVH1 domain-binding motifs separately or together, co-expression of mutant protein with WASF3 resulted in smaller ciliary tip membrane expansions. Finally, inactivation of the lipid modification on the cysteine residue at amino acid position 3 also caused a moderate decrease in the sizes of ciliary tip expansions. Taken together, our data illustrate the importance of amino acid motifs and domains within PCARE in fulfilling its physiological function.

PurposeThe unfolded protein response (UPR) is triggered when the protein folding capacity of the endoplasmic reticulum (ER) is overwhelmed and misfolded proteins accumulate in the ER, a condition referred to as ER stress. IRE1α is an ER-resident protein that plays major roles in orchestrating the UPR. Several lines of evidence implicate the UPR and its transducers in neurodegenerative diseases, including retinitis pigmentosa (RP), a group of inherited diseases that cause progressive dysfunction and loss of rod and cone photoreceptors. This study evaluated the contribution of IRE1α to photoreceptor development, homeostasis, and degeneration.MethodsWe used a conditional gene targeting strategy to selectively inactivate Ire1α in mouse rod photoreceptors. We used a combination of optical coherence tomography (OCT) imaging, histology, and electroretinography (ERG) to assess longitudinally the effect of IRE1α deficiency in retinal development and function. Furthermore, we evaluated the IRE1α-deficient retina responses to tunicamycin-induced ER stress and in the context of RP caused by the rhodopsin mutation RhoP23H.ResultsOCT imaging, histology, and ERG analyses did not reveal abnormalities in IRE1α-deficient retinas up to 3 months old. However, by 6 months of age, the Ire1α mutant animals showed reduced outer nuclear layer thickness and deficits in retinal function. Furthermore, conditional inactivation of Ire1α in rod photoreceptors accelerated retinal degeneration caused by the RhoP23H mutation.ConclusionsThese data suggest that IRE1α is dispensable for photoreceptor development but important for photoreceptor homeostasis in aging retinas and for protecting against ER stress-mediated photoreceptor degeneration.

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient’s case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.

Inhibition of poly-ADP-ribose polymerase 1 (PARP1) could relieve phosphodiesterase 6 mutation-induced retinitis pigmentosa (RP). However, the mechanism related to PARP1 overexpression in the RP has not been clarified. We attempted to explore the potential mechanism related to PARP1 regulating RP.ATAC-seq and RNA-seq were performed for retina tissues of C3H and rd1 mice. The differentially expressed genes (DEGs) were identified, followed by the construction of PARP1-DEG co-expression and protein-protein interaction (PPI) networks. Gene ontology-biological process and pathway enrichment of DEGs were performed by clusterProfiler software. The overlapped genes that might play regulatory roles in PARP1 expression were mined by integrated analysis of RNA-seq and ATAC-seq data.A total of 1061 DEGs were identified between C3H and rd1 group. Co-expression network was constructed with 313 PARP1-gene co-expression pairs. The down-regulated DEGs were closely related to visual perception and light stimulus-related biological process, while the up-regulated DEGs were significantly enriched in phototransduction and PPAR signaling pathway. PPI network was constructed with 202 nodes and 375 edges, which was clustered into 3 modules. Module 1 genes were closely related to detection of light stimulus, visual perception related biological process and phototransduction pathway (involved with Gnat1/Guca1b/Gnat2/Sag/Pde6g). By integrated analysis of the RNA-seq and ATAC-seq, the overlapped up-regulated genes were Asxl3 and Nyap2, while the down-regulated genes were Tmem136 and Susd3.Gnat1 may play a key role in RP development by interacting with PARP1. Susd3 may play a regulatory role in PARP1 expression and affect RP formation.

To investigate the presence and clinical relevance of hyperreflective foci (HRFs) in retinitis pigmentosa.Seventy seven retinitis pigmentosa cases were retrospectively reviewed. The 10-mm wide cross-line macular scans in optical coherence tomography were acquired. Hyperreflective foci were classified according to the location in optical coherence tomography: outer layers within the macula (HRF-outer-central), macular border beyond the central 3 mm (HRF-outer-perifoveal), and choroid (HRF-choroidal). The visual acuity at baseline, at 12 months, and other fundus characteristics were collected.The mean logMAR best-corrected visual acuity decreased from 0.59 ± 0.66 (20/78 in Snellen) to 0.74 ± 0.81 (20/106 in Snellen) in 1 year. Sixty-six (42.9%), 105 (68.2%), and 98 (63.6%) eyes were classified to HRF-outer-central, HRF-outer-perifoveal, and HRF-choroidal group, respectively. Hyperreflective foci were positively correlated with poorer vision, central macular thinning, and ellipsoid zone disruption (all P0.001). Worse vision was associated with older age, macular involvement, and the coexistence of two or three HRF groups (P = 0.014, 0.047, 0.019,0.001, respectively). Hyperreflective foci developed more frequently in patients with thick choroid than in those with thin choroid. The coexistence of three HRF groups was correlated with quicker visual deterioration (P = 0.034).Hyperreflective foci are common in retinitis pigmentosa and can be a negative prognostic indicator of macular thickness and visual preservation. Thick choroid was associated with all groups of HRFs, especially HRF-choroidal.

Retinol dehydrogenase 11 (RDH11) is an 11-cis-retinol dehydrogenase that has a well-characterized, albeit auxiliary role in the retinoid cycle. Diseases caused by mutations in the RDH11 gene are very rare, and only one affected family with eye and intelligence involvement has been reported. In the present study, we describe the clinical and genetic findings in a Chinese patient with retinitis pigmentosa (RP), juvenile cataracts, intellectual disability, and myopathy. Trio-based whole-exome sequencing and whole genomic copy number variation detection were performed in this family, and compound heterozygous mutations were identified in RDH11 of the patient: c.938TC (p.Leu313Pro) derived from the father and c.75-3CA derived from the mother. Variant c.75-3CA was confirmed to be a splice-site mutation by cDNA sequencing. It caused exon 2 skipping, resulting in a frameshift mutation and premature translation termination (p.Lys26Serfs*38). Moreover, we found mislocalization of RDH11 protein in muscle cells of the patient by using immunofluorescence staining. This is the first case reported in the Chinese population harboring mutations in RDH11 and revealing a new phenotype of syndromic RP with myopathy.

Background. New pathogenetic treatment options, such as gene therapy, are now used to treat previously uncurable diseases. However, price of such treatment is high, especially in the case of orphan diseases, where costs may many-fold exceed the prices for other types of medication. This raises a question of optimal way of financing gene therapy in Russia.Objective: to evaluate economic consequences of centralizing procurement of gene therapy in 2021–2030 in the case of the drug indicated for treatment of biallelic RPE65 mutation-associated retinal dystrophy.Material and methods. Voretigene neparvovec is a new gene therapy that is used to treat RPE65 mutation-associated Leber congenital amaurosis and isolated retinitis pigmentosa. We estimated the number of patients (children and adults) that could be treated with voretigene neparvovec in 2021–2030 in Russia using demographic forecasting method, literature and expert data. Budget costs of treatment were estimated for two scenarios: status-quo, where gene therapy is purchased by regions for higher price, and centralized scenario with federal procurements and lower price for the drug.Results. Up to 100 children and 56 adults could be treated with voretigene neparvovec in 2021–2030 in Russia. Centralizing procurements at the expense of federal budget may save up to 20.7% or 1.8 billion rub. (1.13 billion rub. for children and 0.67 billion rub. for adults), compared to regional procurements.Conclusion. Centralizing procurements of expensive drugs intended for gene therapy of orphan diseases may save budget costs of the Russian Federation, compared to status-quo decentralized purchases.

Purpose To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope. Methods PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era. Results In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1 and JNK. In retinoblastoma, curcumin inhibits proliferation, migration and apoptosis of RBY79 and SO-RB50. Curcumin has already proven its efficacy in inhibiting viral replication, coagulation and cytokine storm in COVID era. Conclusion Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.

Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange (human numbering) located in the 310 helix of the C2A domain of RIMS1/RIM1 (Rab3-interacting molecule 1). RIM is an evolutionarily conserved multi-domain protein and essential component of presynaptic active zones, which is centrally involved in fast, Ca2+-triggered neurotransmitter release. How the CORD7 mutation affects synaptic function has remained unclear thus far. Here, we established Drosophila melanogaster as a disease model for clarifying the effects of the CORD7 mutation on RIM function and synaptic vesicle release. To this end, using protein expression and X-ray crystallography, we solved the molecular structure of the Drosophila C2A domain at 1.92 Å resolution and by comparison to its mammalian homologue ascertained that the location of the CORD7 mutation is structurally conserved in fly RIM. Further, CRISPR/Cas9-assisted genomic engineering was employed for the generation of rim alleles encoding the R915H CORD7 exchange or R915E, R916E substitutions (fly numbering) to effect local charge reversal at the 310 helix. Through electrophysiological characterization by two-electrode voltage clamp and focal recordings we determined that the CORD7 mutation exerts a semi-dominant rather than a dominant effect on synaptic transmission resulting in faster, more efficient synaptic release and increased size of the readily releasable pool but decreased sensitivity for the fast calcium chelator BAPTA. In addition, the rim CORD7 allele increased the number of presynaptic active zones but left their nanoscopic organization unperturbed as revealed by super-resolution microscopy of the presynaptic scaffold protein Bruchpilot/ELKS/CAST. We conclude that the CORD7 mutation leads to tighter release coupling, an increased readily releasable pool size and more release sites thereby promoting more efficient synaptic transmitter release. These results strongly suggest that similar mechanisms may underlie the CORD7 disease phenotype in patients and that enhanced synaptic transmission may contribute to their increased cognitive abilities.

Purpose To evaluate macular vascular abnormalities in patients with macular dystrophies (MD) and retinitis pigmentosa (RP) through application of optical coherence tomography angiography (OCT-A). Methods In this retrospective study, patients with MD and RP were examined by OCT-A and compared to healthy individuals. OCT-A images were analyzed regarding the diameter and surface area of the foveal avascular zone (FAZ) as well as flow (FL) in different retinal layers (superficial vascular complex (SVC), intermediate capillary complex (ICP), deep capillary complex (DCP), choriocapillaris (CC), and choroid (CD)). Results Twenty-one patients with MD, 21 patients with RP without macular edema (RPnE), 8 patients with RP with edema (RPwE), and 41 healthy individuals were enrolled. The group of MD and RPnE patients showed none or only minor changes in FAZ. In RPwE patients, the FAZ was significantly smaller in vertical and horizontal measurements and surface area in SVC, whereas it was markedly enlarged in ICP. FL was significantly reduced compared to healthy individuals by an average of 13.2% in CD, 14.2% in CC, and 8.4% in DCP in all patient groups. In ICP, the reduction was 9.2% for RPnE and 12.7% for RPwE patients. The SVC showed reduced FL in the MD (8.1%) and RPnE (10.3%) group. Conclusions OCT-A is a valuable tool to examine retinal vascular abnormalities in patients with MD and RP. OCT-A revealed a reduced flow in various retinal layers in MD, RPnE, and RPwE. Alterations of the FAZ were less distinct in these groups which add to the variation reported previously.

Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive inherited disorder. Missed diagnosis might happen in clinical works due to an unclear genotype–phenotype correlation. We analyzed two families visiting our center; the parents are normal; each of the family aborted a fetus at 12WG. Following ultrasonography and pathological examination, both were diagnosed as MKS. Whole exome sequencing identified a compound heterozygous of two novel variants of CEP290 and a heterozygous of a novel variant of CC2D2A. Frameshift mutations in ZNF77 were also detected. Western blot analyzing whole-brain tissue showed that the expression of ZNF77, CC2D2A, and CEP290 was enhanced. HEK293T transfected with over-expression wildtype/mutated ZNF77 plasmid showed that SHH was increased in wildtype ZNF77 cells, while SHH and CC2D2A were increased in mutated ZNF77 cells. Our research provided two novel pathogenic variants of CEP290 and CC2D2A and suggested that ZNF77 might promote the expression of CC2D2A and regulate the amount of SHH.

Twelve cases of adult-onset blindness were identified in a flock of 130 polled Wiltshire sheep in New Zealand over a 3-year period. Affected sheep developed night blindness between 2 and 3 years of age, which progressed to complete blindness by 4 to 5 years of age. Fundic examination findings included progressive tapetal hyperreflectivity and attenuation of retinal blood vessels. Histologically, the retinas had a selective loss of rod photoreceptors with initial preservation of cone photoreceptors. Retinal degeneration was not accompanied by any other ocular or central nervous system abnormalities, and pedigree analysis suggested an inherited basis for the disease. Mating an affected Wiltshire ram to 2 affected Wiltshire ewes resulted in 6 progeny that all developed retinal degeneration by 2 years of age, while mating of the same affected ram to 6 unaffected ewes resulted in 8 unaffected progeny, consistent with autosomal recessive inheritance. Homozygosity mapping of 5 affected Wiltshire sheep and 1 unaffected Wiltshire sheep using an OvineSNP50 Genotyping BeadChip revealed an identical-by-descent region on chromosome 5, but none of the genes within this region were considered plausible candidate genes. Whole-genome sequencing of 2 affected sheep did not reveal any significant mutations in any of the genes associated with retinitis pigmentosa in humans or progressive retinal atrophy in dogs. Inherited progressive retinal degeneration affecting rod photoreceptors has not been previously reported in sheep, but this disease has several similarities to inherited retinal dystrophies in other species.

Item does not contain fulltext PURPOSE: This study aimed to investigate the clinical and genetic aspects of solute carrier (SLC) genes in inherited retinal diseases (IRDs). METHODS: Exome sequencing data were filtered to identify pathogenic variants in SLC genes. Analysis of transcript and protein expression was performed on fibroblast cell lines and retinal sections. RESULTS: Comprehensive analysis of 433 SLC genes in 913 exome sequencing IRD samples revealed homozygous pathogenic variants in 6 SLC genes, including 2 candidate novel genes, which were 2 variants in SLC66A1, causing autosomal recessive retinitis pigmentosa (ARRP), and a variant in SLC39A12, causing autosomal recessive mild widespread retinal degeneration with marked macular involvement. In addition, we present 4 families with ARRP and homozygous null variants in SLC37A3 that were previously suggested to cause retinitis pigmentosa, 2 of which cause exon skipping. The recently reported SLC4A7- c.2007dup variant was found in 2 patients with ARRP resulting in the absence of protein. Finally, variants in SLC24A1 were found in 4 individuals with either ARRP or congenital stationary night blindness. CONCLUSION: We report on SLC66A1 and SLC39A12 as candidate novel IRD genes, establish SLC37A3 pathogenicity, and provide further evidence of SLC4A7 as IRD genes. We extend the phenotypic spectrum of SLC24A1 and suggest that its ARRP phenotype may be more common than previously reported.

Child health is a global health priority. The program “Elimination of Eliminable Blindness in the World of Vision-2020” gives the fourth place to the problems of pediatric ophthalmopathology and creates targeted programs for their elimination. The introduction of modern equipment in the clinical practice of pediatric ophthalmologists has expanded the boundaries of traditional diagnostics. Microperimetry is an innovative, quantitative, non-invasive diagnostic study aimed at assessing the functional ability of the retina in strict correlation with morphology. Along with the assessment of light sensitivity, the device allows you to measure fixation parameters, which serves as a reliable criterion for its stability and indirectly reflects the functional organization of central vision. In this regard, the literature review presents the results of domestic and foreign researchers who used microperimetric testing as the main or additional research method for diseases of various etiologies, such as hereditary retinal diseases, amblyopia, and nystagmus. Most authors have demonstrated the high diagnostic significance of this method, the ability to assess photosensitivity of the retina, the detection of fixation disorders, such as eccentricity and instability, even in pediatric patients. The use of microperimetry as a new method of treatment for these diseases has also been shown. Visual rehabilitation based on biofeedback provided by this device has shown high efficiency in diseases of the central region. More research remains to be done to determine future potential applications of this technology, in particular in pediatric practice, and to develop the potential of microperimetry as a tool for the visual rehabilitation of patients.

Retinitis pigmentosa (RP) is the most recognized inherited retinal disorder involving progressive photoreceptors degeneration which eventually causes blindness. However, the pathogenesis of RP is still unclear, making it difficult to establish satisfying treatments. Evidence have been found to support the theory that vascular dysfunction is associated with the progression of RP. Optical coherence tomography angiography (OCTA) is a newly developed technology that enables visualization as well as quantitative assessment of retinal and choroidal vasculature non-invasively. Advances in OCTA have opened a window for in-depth understanding of RP pathogenesis. Here, we propose a hypothesis of RP pathogenesis based on the current OCTA findings in RP, which includes four stages and two important key factors, vascular dysfunction and microglia activation. Further, we discuss the future animal experiments needed and how advanced OCTA technology can help to further verity the hypothesis. The final goal is to explore potential treatment options with enhanced understanding of RP pathogenesis.

BACKGROUND: Clinical trials for retinitis pigmentosa (RP) likely require long follow-ups because of the slow progression of RP. Understanding patients’ attitudes toward participation in a long trial and their acceptability of strategies aimed at promoting retention/compliance is important for assessing feasibility and resource needs and optimizing trial design. METHODS: A crowdsourcing survey to adult RP patients was administered on social media in 2020 July-November. Patient enthusiasm level of study participation, acceptability of attending clinic visits every 4–5 months for 45-months, tele-visits with doctors, and of receiving text messages for medication reminders and for reporting missed dosages were surveyed. RESULTS: Among the 1473 respondents, over 95% use email or a mobile phone and receive text messages; 1157 (79%) respondents were very/somewhat enthusiastic about participation, among them, 80.6% were “very willing” to attend clinic visits every 4–5 months for 45 months; 90.3% were “very willing” to have tele-visits; 64.7% and 77.1% were willing to receive text reminders to take medication and messages surveying missed doses, respectively. The youngest age group (18–30) (22.1%) and oldest age group (70+) (26.1%) compared to the 41–50 years age group (14%) and women (23.5%) compared to men (14.2%) were statistically significantly more likely not to report high willingness to participate in clinical visits for 45 months. CONCLUSIONS: A trial requiring 4-years of commitment is feasible although retention can be challenging. Strategies including supplementing in-clinic visits with tele-visits and frequent communications may facilitate retention. This study also demonstrates a methodology useful for planning clinical trials for chronic diseases.

A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected of USH2A-associated disease and no or mono-allelic USH2A variants using whole genome sequencing (WGS) followed by an improved pipeline for variant interpretation to provide a conclusive diagnosis. One hundred subjects were screened using WGS to identify causative variants in USH2A or other USH/arRP-associated genes. In addition to the existing variant interpretation pipeline, a particular focus was put on assessing splice-affecting properties of variants, both in silico and in vitro. Also structural variants were extensively addressed. For variants resulting in pseudoexon inclusion, we designed and evaluated antisense oligonucleotides (AONs) using minigene splice assays and patient-derived photoreceptor precursor cells. Biallelic variants were identified in 49 of 100 subjects, including novel splice-affecting variants and structural variants, in USH2A or arRP/USH-associated genes. Thirteen variants were shown to affect USH2A pre-mRNA splicing, including four deep-intronic USH2A variants resulting in pseudoexon inclusion, which could be corrected upon AON treatment. We have shown that WGS, combined with a thorough variant interpretation pipeline focused on assessing pre-mRNA splicing defects and structural variants, is a powerful method to provide subjects with a rare genetic condition, a (likely) conclusive genetic diagnosis. This is essential for the development of future personalized treatments and for patients to be eligible for such treatments.

SUMMARY OBJECTIVE: Retinitis pigmentosa is an inherited degenerative disorder causing severe retinal dystrophy and visual impairment, mainly with onset in the first or second decades. The next-generation sequencing has become an efficient tool to identify disease-causing mutations in retinitis pigmentosa. The aim of this retrospective study was to investigate novel gene variants and evaluate the utility of whole-exome sequencing in patients with retinitis pigmentosa. METHODS: The medical records of 20 patients with retinitis pigmentosa at Eskişehir City Hospital between September 2019 and February 2022 were analyzed retrospectively. Peripheral venous blood was obtained, followed by the extraction of genomic DNAs. The medical and ophthalmic histories were collected, and ophthalmological examinations were performed. Whole-exome sequencing was performed to determine the genetic etiology of the patients. RESULTS: The proportion of genetically solved cases was 75% (15/20) in the patients with retinitis pigmentosa. Molecular genetic testing identified 13 biallelic and 4 monoallelic mutations in known retinitis pigmentosa genes, including 11 novel variants. According to in silico prediction tools, nine variants were predicted as pathogenic or possibly pathogenic. We identified six previously reported mutations to be associated with retinitis pigmentosa. The age of onset of the patients ranged from 3 to 19, with a mean age of onset of 11.6. All patients had a loss of central vision. CONCLUSION: As the first study of the application of whole-exome sequencing among patients with retinitis pigmentosa in a Turkish cohort, our results may contribute to the characterization of the spectrum of variants related to retinitis pigmentosa in the Turkish population. Future population-based studies will enable us to reveal the detailed genetic epidemiology of retinitis pigmentosa.

Retinitis pigmentosa (RP) affects approximately 1 in 4000 individuals. It has many different genetic etiologies and therefore diagnosis can be challenging. Understanding the different testing methodologies is beneficial for clinicians and researchers in order to select the best testing method, whether it be panel testing, whole exome sequencing, or whole genome sequencing for individuals affected with RP. The Methods section also outlines the steps required to complete a WES assay, which has become a popular method for identifying the molecular diagnosis for individuals with RP.

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.

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.

Medmont Dark-Adapted Chromatic (DAC) Perimeter enables efficient and quantifiable evaluation of rod-mediated (scotopic) vision. DAC tests rod function at multiple retinal locations, creating a topographical map of rod-mediated vision. These dynamic rod responses can be used as a functional marker to monitor disease progression and functional alterations in inherited retinal dystrophies, such as retinitis pigmentosa, Stargardt disease, cone-rod dystrophy, and choroideremia. In this chapter, we describe a protocol for the operation and analysis of the Medmont DAC in monitoring and assessing various retinal disorders.

The application of metabolomics in ophthalmology helps to identify new biomarkers and elucidate disease mechanisms in different eye diseases, as well as aiding in the development of potential treatment options. Extracting metabolites successfully is essential for potential further analysis using mass spectrometry. In this chapter, we describe how to extract metabolites from a variety of sources including (1) cells on a dish, (2) cell culture medium, and (3) tissues in vivo with and without stable isotope tracers. Samples prepared using this protocol are suitable for a range of downstream mass spectrometry analyses and are stable in solvent for weeks at -80 °C.

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy. There are three main characteristics of RP: night blindness, retinal pigmentation, and visual field constriction. Among these three features, night blindness was the first to be discovered, which could be dated back to the ancient Egyptians at around 1500 BC. However, the night blindness described at that time was most likely associated with vitamin A deficiency rather than RP. Retinitis pigmentosa was first described in cadaver anatomic dissection before the invention of the ophthalmoscope. However, it was not linked to RP or night blindness. It was not until the invention of the ophthalmoscope that ophthalmologists could truly look into the eye and correlate the retinal pigmentation with clinical symptoms, such as night blindness and visual field constriction. In 1983, at a RP workshop that gathered together many experts, a consensus was reached regarding the terminology and guidelines for the diagnosis of RP. In this chapter, we will introduce the history and discovery of RP along with its characteristics.

Ocular gene therapy represents an emerging and promising therapeutic approach for the treatment of several of the inherited retinal diseases. Currently, the focus has been to investigate monogenic inherited retinal disorders. Genetic and cellular therapies can be delivered to the eye by various injection techniques, including those that are intravitreal, subretinal, and suprachoroidal. Each of these three delivery methods are discussed with regard to their historical background, indications, surgical steps, and follow-up.

Viral vectors are employed in gene therapy to deliver functional genes. It is often traceable in bodily secretions and excretions of the recipients. Methods of collecting, processing, and storing specimens need to be standardized to ensure effective regulation and monitoring of vector safety. Furthermore, these regulations are crucial in upholding the safety and efficacy of clinical trials and subsequent delivery of these treatments. This chapter discusses vector immunogenicity monitoring and methods of lacrimal, saliva, urine, blood, and serum sampling in patients with retinitis pigmentosa before and throughout the delivery of adeno-associated virus-based gene therapy.

With an estimated prevalence of 1 in 4000 worldwide [1], retinitis pigmentosa (RP) comprises a spectrum of progressive inherited retinal disorders that can lead to blindness as early as age 30 [2]. Despite its relatively high prevalence and devastating consequences, RP does not have a definitive cure. Therapeutic attempts have been made with nutritional supplementation, but these strategies only have proven benefit in a limited number of patients with rare forms of RP. Thus, current standards of care involve regular follow-up, management of associated ocular pathology such as macular edema and cataracts, and genetic counseling and low vision rehabilitation. In recent years, gene therapy, visual prostheses, and stem cell therapy have emerged as FDA-approved treatments for RP, but these options are not yet widely used. Herein, this chapter will discuss the therapeutic strategies listed above that comprise the current standards of care and briefly discuss some emerging options.