Retinitis Pigmentosa Patients Research Articles

Genotypic and phenotypic characterization of a cohort of patients affected by rod CNG channel-associated retinitis pigmentosa.

Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study is to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations. The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (Low and High group). In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between Low and High groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between Low and High groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients. Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies.

Disease modeling and pharmacological rescue of autosomal dominant retinitis pigmentosa associated with RHO copy number variation

Retinitis pigmentosa (RP), a heterogenous group of inherited retinal disorder, causes slow progressive vision loss with no effective treatments available. Mutations in the rhodopsin gene (RHO) account for ~25% cases of autosomal dominant RP (adRP). In this study, we describe the disease characteristics of the first-ever reported mono-allelic copy number variation (CNV) in RHO as a novel cause of adRP. We (a) show advanced retinal degeneration in a male patient (68 years of age) harboring four transcriptionally active intact copies of rhodopsin, (b) recapitulated the clinical phenotypes using retinal organoids, and (c) assessed the utilization of a small molecule, Photoregulin3 (PR3), as a clinically viable strategy to target and modify disease progression in RP patients associated with RHO-CNV. Patient retinal organoids showed photoreceptors dysgenesis, with rod photoreceptors displaying stunted outer segments with occasional elongated cilia-like projections (microscopy); increased RHO mRNA expression (quantitative real-time PCR [qRT-PCR] and bulk RNA sequencing); and elevated levels and mislocalization of rhodopsin protein (RHO) within the cell body of rod photoreceptors (western blotting and immunohistochemistry) over the extended (300 days) culture time period when compared against control organoids. Lastly, we utilized PR3 to target NR2E3, an upstream regulator of RHO, to alter RHO expression and observed a partial rescue of RHO protein localization from the cell body to the inner/outer segments of rod photoreceptors in patient organoids. These results provide a proof-of-principle for personalized medicine and suggest that RHO expression requires precise control. Taken together, this study supports the clinical data indicating that RHO-CNV associated adRPdevelops as a result of protein overexpression, thereby overloading the photoreceptor post-translational modification machinery.

Understanding the relationship between pachychoroid spectrum disorders and retinitis pigmentosa: A review of the evidence.

This study aims to investigate the relationship between pachychoroid spectrum disorders and retinitis pigmentosa (RP) or rod-cone dystrophy through a comprehensive literature review. The purpose is to explore the association between these disorders, understand their underlying mechanisms, and summarize the existing hypotheses and opinions. A thorough review of the literature was conducted using PubMed, focusing on articles related to central serous chorioretinopathy (CSC), RP, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, focal choroidal excavation, peripapillary pachychoroid neovasculopathy, and peripheral exudative hemorrhagic chorioretinopathy. Relevant studies were selected for a detailed narrative review and analysis. Several studies have reported the coexistence of CSC and RP, indicating a potential association between the two conditions. The dysfunction of the retinal pigment epithelium is proposed as a common factor. Choroidal thinning is observed in RP, but conflicting results exist regarding choroidal thickness (CT). While some studies support choroidal thinning in RP, others suggest preserved or increased thickness. Additionally, cases of pachychoroid neovasculopathy and polypoidal choroidal vasculopathy in RP have been reported, suggesting an overlap between these conditions. The literature suggests conflicting reports on CT changes in RP. Future research should focus on large-scale studies using comprehensive imaging techniques, genetic analysis, and long-term follow-up to uncover the underlying mechanisms and determine the prevalence of pachychoroid spectrum disorders in RP patients.

Simulating vision impairment in virtual reality: a comparison of visual task performance with real and simulated tunnel vision

In this work, we explore the potential and limitations of simulating gaze-contingent tunnel vision conditions using Virtual Reality (VR) with built-in eye tracking technology. This approach promises an easy and accessible way of expanding study populations and test groups for visual training, visual aids, or accessibility evaluations. However, it is crucial to assess the validity and reliability of simulating these types of visual impairments and evaluate the extend to which participants with simulated tunnel vision can represent real patients. Two age-matched participant groups were acquired: The first group (n = 8, aged 20–60, average 49.1 ± 13.2) consisted of patients diagnosed with Retinitis pigmentosa (RP). The second group (n = 8, aged 27–59, average 46.5 ± 10.8) consisted of visually healthy participants with simulated tunnel vision. Both groups carried out different visual tasks in a virtual environment for 30 min per day over the course of four weeks. Task performances as well as gaze characteristics were evaluated in both groups over the course of the study. Using the ’two one-sided tests for equivalence’ method, the two groups were found to perform similar in all three visual tasks. Significant differences between groups were found in different aspects of their gaze behavior, though most of these aspects seem to converge over time. Our study evaluates the potential and limitations of using Virtual Reality technology to simulate the effects of tunnel vision within controlled virtual environments. We find that the simulation accurately represents performance of RP patients in the context of group averages, but fails to fully replicate effects on gaze behavior.

Prognostic impact of hyperreflective foci in nonsyndromic retinitis pigmentosa.

To evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP). Retrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded. A total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01). HRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area.

Comparison of Full-Field Stimulus Threshold Measurements in Patients With Retinitis Pigmentosa and Healthy Subjects With Dilated and Nondilated Pupil.

The common protocol of full-field stimulus threshold (FST) testing recommends pupil dilation. The aim of this study is to investigate the difference between FST measurements with dilated and nondilated pupils in healthy subjects and patients with retinitis pigmentosa (RP). Twenty healthy subjects and 20 RP patients were selected. One pupil of each subject was dilated; the other eye was measured in physiological width of the pupil. The FST was conducted using Diagnosys Espion E2/E3 with white, blue, and red stimuli. Statistical analysis was conducted with a mixed-model analysis of variance and a paired t-test. The statistical analysis revealed a significant difference between measurements of dilated and nondilated pupils with the following: blue stimuli for all subjects and groups except those with highly progressed RP; white stimuli for all tested subjects in total, for RP patients with better-preserved visual field (VF), and rod-mediated FST response; and red stimuli for RP patients with better-preserved VF and rod-mediated FST response. On average, the difference between the FST values for RP patients were -3.2 ± 3dB for blue, -2.3 ± 2.9dB for white, and -0.83 ± 3dB for red stimuli. The correlation between the FST values of dilated and nondilated pupils with all three stimuli was linear. Current recommendations are to perform FST with dilated pupils. However, based on this study's findings, pupil dilation can be omitted for clinical diagnostics or rough follow-ups. Our data provide useful information for the clinical use of FST.

Generation of an induced pluripotent stem cell line (SJTUGHi001-A) from a patient with Retinitis Pigmentosa carrying c.77C > T mutation in RAX2 gene

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinopathy resulting in irreversible loss of vision. Mutations in RAX2 gene has been related to RP with mechanisms unclear. Here, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a RP patient carrying c.77C > T mutation in RAX2 gene. This cell line was induced by integration-free episomal vectors and validated for pluripotency and differentiation capacity, which may serve as a model to study the role of RAX2 in RP pathogenesis.

Evaluation of Full-Field Stimulus Threshold Test Results in Retinitis Pigmentosa: Relationship with Full-Field Electroretinography, Multifocal Electroretinography, Optical Coherence Tomography, and Visual Field.

The full-field stimulus threshold (FST) test was developed to evaluate the efficacy and safety of treatments of hereditary retinal diseases. In this study we performed the FST test in patients with retinitis pigmentosa (RP) and compared the results with findings from other ophthalmological tests. The study included 51 intermediate and advanced RP patients and 21 normal subjects. All patients and controls underwent routine examination and ophthalmological tests including visual field, optical coherence tomography, full-field and multifocal electroretinography (mfERG), and FST tests. During FST testing, the perception thresholds of retina to the white, blue, and red FST were determined in decibels. The mean age of the patients and the controls were 35.2 and 33.5 years, respectively. For all RP patients, no response was obtained on full-field ERG. All subjects were able to perform reliable FST tests. The mean values of visual acuity and central macular thickness were significantly lower and visual field mean deviation values were significantly higher in the RP group than the controls. When we evaluated the mfERG findings, the mean P1 wave amplitudes in all rings were significantly lower and the mean peak times were significantly longer in RP patients than controls. In comparisons of FST test results, the mean values for white, blue, red and the difference between blue-red thresholds were significantly lower in the RP group than the control group. The FST test is a fast and a reliable exam which can be done in subjects with poor visual acuity and reduced visual field. The results of this study confirm that the FST test can measure retinal sensitivity in severely affected RP subjects with flat flash ERG.

MANAGEMENT APPROACH OF LOW VISION IN RETINITIS PIGMENTOSA: WHAT SHOULD WE DO?

Introduction : Retinitis pigmentosa is a chronic and progressive disease throughout patient’s life. Management low vision in retinitis pigmentosa patients are to maximize their remaining vision and provision of visual aids, it can be financial dan social burden.&#x0D; Case Illustration : A 56-year-old man came with blurred vision in his both eyes for 12 years. The patient had cataract surgeries and IOLs implantation in 2022. Ophthalmologic examination revealed the right eye was 4/40 and the left eye was 3/60. Funduscopic examination revealed the bone spicule appearance, blood vessel attenuation, and waxy disc pallor in both eyes. Contrast sensitivity test decreased and Farnsworth hue test showed mild to severe. Humphrey visual field examination showed peripheral visual field defect, therefore patient diagnosed with low vision caused by retinitis pigmentosa with bilateral pseudophakia and his Low Vision Quality of Life was intermediate.&#x0D; Discussion : Treatment includes pharmacological treatment with supplementation, optical or non-optical treatment, and rehabilitation. Spectacles clarified distant and near vision with Best Corrected Visual Acuity 6/30 with photochromic lenses, for adapting the light and gave addition lens +5.00 in both eyes. Rehabilitation enhances his head tracking, scanning, and habitual spotting skills. Lighting and typoscope would help his daily reading activities as well.&#x0D; Conclusion : Low vision requires several management approach, patient with visual impairment can get low vision aids to optimize his visual function based on his needs. Managing low vision in patient with visual impairment has to be considered from multiple aspects.

Establishment of the induced pluripotent stem cell line SJTUGHi002-A from a CNGA1-related recessive retinitis pigmentosa patient

Retinitis pigmentosa (RP) is the most common inherited retinal diseases, characterized by photoreceptor cell death and retinal pigment epithelial atrophy. Mutations in cyclic nucleotide gated channel subunit alpha 1 (CNGA1) have been reported to cause retinitis pigmentosa. Here, we established the human induced pluripotent stem cell line (iPSC) SJTUGHi002-A, generated from peripheral blood mononuclear cells of a 36-year-old male RP patient, who carried a homozygous frameshift variant in CNGA1 gene (c.265delC; p.L89Ffs*4). The cell line can serve as a patient-derived disease model for exploring the pathogenesis and drug development of CNGA1-RP.

IFT27 regulates the long-term maintenance of photoreceptor outer segments in zebrafish

Approximately a quarter of Retinitis Pigmentosa (RP) is caused by mutations in transport-related genes in cilia. IFT27 (Intraflagellar Transport 27), a core component of the ciliary intraflagellar transport (IFT) system, has been implicated as a significant pathogenic gene in RP. The pathogenic mechanisms and subsequent pathology related to IFT27 mutations in RP are largely obscure. Here, we utilized TALEN technology to create an ift27 knockout (ift27-/-) zebrafish model. Electroretinography (ERG) detection showed impaired vision in this model. Histopathological examinations disclosed that ift27 mutations cause progressive degeneration of photoreceptors in zebrafish, and this degeneration was late-onset. Immunofluorescence labeling of outer segments showed that rods degenerated before cones, aligning with the conventional characterization of RP. In cultured human retinal pigment epithelial cells, we found that IFT27 was involved in maintaining ciliary morphology. Furthermore, decreased IFT27 expression resulted in the inhibition of the Hedgehog (Hh) signaling pathway, including decreased expression of key factors in the Hh pathway and abnormal localization of the ciliary mediator Gli2. In summary, we generated an ift27-/- zebrafish line with retinal degeneration which mimicked the symptoms of RP patients, highlighting IFT27′s integral role in the long-term maintenance of cilia via the Hh signaling pathway. This work may furnish new insights into the treatment or delay of RP caused by IFT27 mutations.

Alteration Ocular Motility in Retinitis Pigmentosa: Case-Control Study.

To evaluate ocular motility (OM) disorders and strabismus in a sample of patients with retinitis pigmentosa (RP) and a control sample. In this cross-sectional retrospective analysis, we studied a sample of RP patients with a mean age of 48.74 years and an average visual acuity of 7/10 based on Snellen optotype and a sample of control patients with similar mean age (49 years [men], 47 years [women]) and sex and an average visual acuity of 9.9/10, with the aim of assessing correlations between alteration of OM and strabismus in RP patients based on age, high refractive defect, or severely impaired binocular vision. The examination followed a protocol of testing for anamnesis and best-corrected visual acuity, as well as a complete eye examination, corneal reflex, cover test, OM, Hess screen, and Lang test. At the first orthoptic evaluation, 45.16% of patients showed strabismus, 41.93% exotropia (25% of cases intermittent), 3.22% esotropia, and 6.45% vertical deviation. Later evaluation showed strabismus in 25.80% of patients, exotropia in 19.35% (9.67% intermittent), esotropia in 3.22%, and vertical deviation in 3.22%. Assessment of eye motility study showed 51.6% overaction of the inferior oblique and hypofunction of the superior rectus, and 18% overaction of the lateral rectus and hypofunction of the medial rectus. According to our results, alterations in OM and strabismus in RP patients are not correlated with age or high refractive defect. Therefore, motility disorders and strabismus are attributed to a genetic factor to which men are more susceptible. The incidence of OM disorder was 77.42%, and strabismus was present in 45.16% of patients.

Genetic profile of syndromic retinitis pigmentosa in Portugal.

Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal. Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology. One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001). This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal.

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

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. 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. 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. 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.

Mesenchymal stem cell therapy in retinitis pigmentosa patients: A systematic review

The current systematic review was aimed at exploring the mesenchymal stem cell (MSC) therapy in retinitis pigmentosa (RP) patients. This study included all the studies which focused and reported the Mesenchymal stem cell therapy in retinitis pigmentosa patients. A filtration procedure was used to remove duplicates, irrelevant publications. The online databases Ovid MEDLINE, Ovid Embase, and the Cochrane Library were used to perform a literature search for publications published between 2016 and 2023, without any date or language restrictions. We used a combination of relevant search terms &amp;quot;MSC, MSC transplantation, Stem cell therapy, Bone marrow-derived stem cell, Adipose tissue-derived stem cell, umbilical cord-derived stem cell, and RP&amp;quot;. We independently identified publications and systematically screened titles, abstracts, and full texts of the collected publications. Eleven trials were evaluated, comprising two preclinical and nine clinical trials assessing mesenchymal stem cells derived from adipose tissue, bone marrow, umbilical cord, and Warton jelly cells. The effectiveness and outcomes of MSC treatment for retinitis pigmentosa varied among different types of MSCs used in therapy. However, the weak evidence regarding the safety of MSCs challenges their promise as a potential treatment for retinitis pigmentosa.

The efficacy and safety of transcorneal electrical stimulation for patients with retinitis pigmentosa: a systematic review and meta-analysis

Retinitis pigmentosa (RP) is a heterogeneous group of genetically inherited degenerative disorders characterized by progressive loss of peripheral vision. Tran&amp;apos;s corneal electrical stimulation (TES) has been proposed as a treatment for various ocular conditions, but its mechanism remains uncertain. This systematic review and meta-analysis aimed to assess the safety and efficacy of trans-corneal electrical stimulation (TcES) as a treatment for RP by comprehensively examining the available literature in medical databases. The literature of the related studies was retrieved from five databases including central, midline, scopus, directory of open access journals, and clinicalTrials.gov. All of the selected scholarly databases were extensively searched online for articles that were published between January 2019 and July 2023. TES was found to be safe for RP patients, with positive effects on the visual field area (VFA) and scotopic b-wave amplitude. It significantly attenuated the annual decline in the visual field hence effectively doubling its half-life from 10 to 20 years. No significant side effects were observed during TES. TES offers a promising treatment option for RP, with potential benefits in slowing disease progression and preserving vision. The OkuStim system and TES present an affordable and adaptable approach, with opportunities for patient self-administration. However, further studies with larger sample sizes and longer durations are needed to confirm these findings and optimize treatment parameters.

Qualifications for Retinitis Pigmentosa and Leber Congenital Amaurosis Patients for Adeno-Associated Viral Gene-Replacement Therapy Clinical Trials

Introduction: This study identifies Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) patients at an Inherited Retinal Disease (IRD) clinic that qualify for ongoing or FDA-approved Adeno-Associated Virus (AAV) gene-replacement therapies. The goal is to demonstrate the benefits of genetic testing at the initial evaluation. Method: A database for RP and LCA patients was curated and clinicaltrials.gov was used to search all ongoing or approved gene-replacement therapies between 1 January 2022 – 1 January 2023. Patients were evaluated for qualification based on the inclusion/exclusion criteria set by each trial. Results: 199 RP and 31 LCA patients were included in the study. Our team identified six AAV gene-replacement therapy clinical trials and the FDA-approved Luxturna®. One hundred fifty-five patients underwent genetic testing and 89 patients had a pathogenic variant identified. A total of 15 patients qualified for one of the proposed trials. Three patients had a biallelic RPE65 mutation and two of them qualified for Luxturna®. All 11 patients with an RPGR mutation qualified for one of the three clinical trials that focused on this gene. Three patients had a c.2991+1655A&gt;G mutation in CEP290 and two of them qualified one of two clinical trials for this gene. Conclusion: Overall, ~10% of patients who had genetic testing qualified for one of the reviewed therapies. A total of 15 patients qualified for an AAV gene-replacement therapy. This study highlights the importance of promoting genetic testing for IRD patients, the need for earlier disease evaluation and the value of continual monitoring of disease progression.

Correlations between the Michigan Retinal Degeneration Questionnaire and visual function parameters in patients with retinitis pigmentosa.

To validate the use of best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD; the difference between BCVA and LLVA), mean macular sensitivity and fixation stability as parameters of vision-related quality of life based on the novel Michigan Retinal Degeneration Questionnaire (MRDQ) in retinitis pigmentosa (RP) patients. In this prospective cross sectional study, 30 patients with RP (47% female) were included with a median age of 41.0 years (interquartile range: 24.1-58.3 years). BCVA, LLVA and LLD were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Mesopic microperimetry was performed to measure mean macular sensitivity and fixation stability. Patients completed a Dutch translation of the MRDQ which results in an experienced disability (Θ-)score of seven domains. Spearman's rank correlation was used. BCVA correlated significantly to the MRDQ domain of central vision (r = 0.657; p < 0.001) and colour vision (r = 0.524; p = 0.003). Lower LLVA significantly correlated to higher experienced disability in the MRDQ domains for central vision (=0.550; p = 0.002) and contrast sensitivity (r = 0.502; p = 0.005). LLD was significantly correlated to the MRDQ domains of scotopic function (r = -0.484; p = 0.007) and mesopic peripheral function (r = -0.533; p = 0.002). Lower mean macular sensitivity was significantly associated with high experienced disability in all domains except for photosensitivity. The majority of the MRDQ domains is strongly associated with visual function parameters. These findings show that visual function measurements, especially LLVA, LLD and mean macular sensitivity on microperimetry, reflect vision-related quality of life and can be used as relevant outcome measures in clinical trials for RP.

Contributed Session I: Correlating cone structure and function in retinitis pigmentosa using coarse-scale optoretinography (CoORG).

Optoretinography (ORG) has the potential to serve as a powerful diagnostic biomarker, owing to its sensitive and objective localization of function and dysfunction. Majority of ORG implementations employ adaptive optics (AO) for imaging activity at a cellular scale. Coarse-scale Optoretinography (CoORG), an ORG paradigm without AO, offers rapid, extended-field recordings and wider applicability in patients with retinal disease, by compromising cellular resolution. This study investigates the feasibility of CoORG in assessing cone dysfunction in patients diagnosed with retinitis pigmentosa (RP). Five RP patients aged 26 - 60 were recruited, alongside age-similar controls. The stimulus for evoking cone activity had a photon density between 15.5x10e6 - 19.7x10e6 photons/μm2, and was centered at 532 ± 5nm. Eight imaging trials per bleach were performed, allowing for 1 min. between successive trials for dark adaptation. The total experimental time for each bleach was 10-20 mins. In RP, cone function, estimated as the change in optical path length in the outer segment in response to a stimulus, was diminished and generally lower than normal controls. This deficit was observed in areas of seemingly normal outer retinal structure. Contrary to normals, no correlation was observed between outer segment length and cone function in RP. This highlights CoORG's potential for early, sensitive detection of retinal dysfunction prior to apparent structural degradation.

Optic Disc Drusen Prevalence in Patients With Retinitis Pigmentosa: A Cross-Sectional Study.

Studies of patients with retinitis pigmentosa (RP) have reported an increased prevalence of optic disc drusen (ODD) compared with the ODD prevalence in the general population. The diagnostic gold standard method for identifying ODD is enhanced depth imaging optical coherence tomography (EDI-OCT), but this modality has not previously been used systematically for identifying ODD in patients with RP. This study aimed to estimate the prevalence of ODD in patients with RP using EDI-OCT. In this cross-sectional study, 40 patients with clinically diagnosed RP aged 18 years or older were included. All patients underwent an ophthalmic examination, including kinetic perimetry, EDI-OCT of the optic nerve head, and fundus photography. Genetic testing with a next-generation sequencing panel of retinal dystrophy genes was performed on the RP patients without a prior genetic diagnosis. Twelve patients (30.0%) had at least one ODD. Six patients had bilateral ODD. No significant differences between patients with and without ODD were found according to age, refraction, best-corrected visual acuity, Bruch membrane opening, or visual field. The genetic variation causing RP was found in 11 of 12 cases in the ODD group and in 17 of 28 cases in the group without ODD. We found the prevalence of ODD in patients with RP to be 30.0%. This is 15 times higher than in the general population and much higher than previously estimated in most studies, potentially indicating that the 2 conditions might be pathogenically related.