Clinical Trials

ALMS and BBS syndromes are rare diseases with overlapping features of multiple sensory and metabolic impairments, including diabetes mellitus. There are to date no specific treatments available and limited information on the natural history of the diseases. the investigators aim to establish a French cohort for these diseases to improve patient care and assess the effect of actual therapies on quality of life. The purpose of this study is to establish a cohort of Bardet-Bield syndrome (BBS) and ALström syndrome (ALMS) patients in order to formalize and address questions concerning the in-depth natural clinical and biological history of the disease on the long term for a given patient, establish the impact on the quality of life of various clinical manifestations

Bardet-Biedl Syndrome (BBS) is a rare genetic disorder associated with a vast array of symptoms. The features of BBS are highly variable, even between siblings, making long-term follow-up and centralization of information vital to better understanding this complex disease and designing effective treatments. Marshfield Clinic has developed the Clinical Registry Investigating Bardet-Biedl Syndrome (CRIBBS) to gather comprehensive health information from patients diagnosed with BBS in a single repository. This information will be used to inform patients, families, and physicians about the complex features of BBS and will serve as a platform for researchers to develop effective and targeted treatment strategies for patients with BBS. CRIBBS is a web-based, confidential database and the privacy of patients enrolled in the registry will always be respected. Information maintained in the database will be identifiable only by an assigned study identification number, not by name. The registry strictly complies with HIPAA regulations. CRIBBS participants may be contacted periodically with information regarding clinical trials or research studies, but participation is entirely voluntary. CRIBBS will bring together complex genetic and clinical information from BBS patients to accelerate research into effective treatments, attract additional researchers, and make it easier for researchers to identify patients and find funding for innovative studies.

Introduction Rare complex syndromes Patients with complex genetic syndromes, by definition, have combined medical problems affecting multiple organ systems, and intellectual disability is often part of the syndrome. During childhood, patients with rare genetic syndromes receive multidisciplinary and specialized medical care; they usually receive medical care from 3-4 medical specialists. Increased life expectancy Although many genetic syndromes used to cause premature death, improvement of medical care has improved life expectancy. More and more patients are now reaching adult age, and the complexity of the syndrome persists into adulthood. However, until recently, multidisciplinary care was not available for adults with rare genetic syndromes. Ideally, active and well-coordinated health management is provided to prevent, detect, and treat comorbidities that are part of the syndrome. However, after transition from pediatric to adult medical care, patients and their parents often report fragmented poor quality care instead of adequate and integrated health management. Therefore, pediatricians express the urgent need for adequate, multidisciplinary adult follow up of their pediatric patients with rare genetic syndromes. Medical guidelines for adults not exist and the literature on health problems in these adults is scarce. Although there is a clear explanation for the absence of adult guidelines (i.e. the fact that in the past patients with rare genetic syndromes often died before reaching adult age), there is an urgent need for an overview of medical issues at adult age, for 'best practice' and, if possible, for medical guidelines. The aim of this study is to get an overview of medical needs of adults with rare genetic syndromes, including: 1. comorbidities 2. medical and their impact on quality of life 3. medication use 4. the need for adaption of medication dose according to each syndrome Methods and Results This is a retrospective file study. Analysis will be performed using SPSS version 23 and R version 3.6.0.

TITLE: Whole genetic approach in Early Genetic Identification of Obesity (WEGIO) DESIGN: Multicenter epidemiological study STUDY POPULATION: Participants at risk for a syndromic or a monogenic genetic obesity, incl. participants clinically diagnosed with Bardet-Biedl-Syndrome (BBS) NUMBER OF PARTICIPANTS: 1000 for initial genetic sequencing and app. 40 for the follow-up documentation COORDINATING INVESTIGATOR: Prof. Dr. Arndt Rolfs

The My Retina Tracker® Registry is sponsored by the Foundation Fighting Blindness and is for people affected by one of the rare inherited retinal degenerative diseases studied by the Foundation. It is a patient-initiated registry accessible via a secure on-line portal at www.MyRetinaTracker.org. Affected individuals who register are guided to create a profile that captures their perspective on their retinal disease and its progress; family history; genetic testing results; preventive measures; general health and interest in participation in research studies. The participants may also choose to ask their clinician to add clinical measurements and results at each clinical visit. Participants are urged to update the information regularly to create longitudinal records of their disease, from their own perspective, and their clinical progress. The overall goals of the Registry are: to better understand the diversity within the inherited retinal degenerative diseases; to understand the prevalence of the different diseases and gene variants; to assist in the establishment of genotype-phenotype relationships; to help understand the natural history of the diseases; to help accelerate research and development of clinical trials for treatments; and to provide a tool to investigators that can assist with recruitment for research studies and clinical trials.

Hepato-renal fibrocystic diseases (HRFD) is a term developed that encompasses rare diseases such as Autosomal Recessive Polycystic Kidney Disease (ARPKD), and other diseases with common features (Joubert syndrome, Bardet Biedl syndrome, Meckel-Gruber syndrome, congenital hepatic fibrosis (CHF), Caroli syndrome (CS), polycystic liver disease, oro-facial-digital syndrome, nephronophithisis (NPHP), and glomerulocystic Kidney Disease). The lack of enough routinely available resources for these diseases to be well diagnosed and treated, would be best resolved by coordinated case accrual and sharing of clinical data and bio-specimens (DNA and tissues) among participating institutions, thereby leading to the centralization and sharing of clinical and genetic information, as well as bio-materials, providing an important engine for more rapid research progress and community understanding through the creation of research networks. This study aims to build a registry of a clinical database (medical health information), a mutational database (genetic information) and an educational resource about HRFD to eventually provide information about these diseases to families, physicians and genetic counselors via our existing HIPAA- approved study website. Goals for the Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource are: 1. \- Clinical Database: • Expand our comprehensive Clinical Database to include information from all patients who meet the inclusion criteria for hepato/renal fibrocystic diseases. 2. \- Mutational Database: * Test children with ARPKD and other hepato/renal fibrocystic disease to identify genetic mutations, establish a DNA bank for patients with hepato/renal fibrocystic diseases and develop a Mutational Database. This Database will be capable of linking clinical and mutational information via a unique identifier in a searchable format to facilitate genetic research (e.g. genotype-phenotype correlations, new disease gene studies, and modifier gene studies), translational studies, and clinical trials. 3- Tissue Resource: * Much of the research that is performed on diseases of the kidney, including recessive genetic diseases, requires human tissue from both affected as well as non-affected (controls) individuals. In this Core Resource, we are establishing an independent tissue resource which would supply investigators throughout North America with samples of hepato/renal fibrocystic disease affected tissues for studies of these disorders. 4- Educational Resource: * Expand our multi-media, web-based resource to provide a reliable up-to-date, and comprehensive informational resource for ARPKD and Hepato/Renal Diseases families, their physicians, and genetic counselors.

Bardet-Biedl syndrome (BBS) and other rare disorders associated with impairment of the melanocortin-4 receptor (MC4R) pathway are characterized by severe early-onset obesity, hyperphagia, and substantial morbidity. Setmelanotide, an MC4R agonist, is approved in Europe for selected genetic obesity disorders and reimbursed in Germany for eligible patients. This study aims to evaluate the effectiveness, safety, treatment persistence, metabolic outcomes, and patient-reported outcomes of Setmelanotide under real-world conditions. The registry is designed to allow future inclusion of additional MC4R agonists as they become approved and clinically available. The study will primarily be conducted at University Hospital Essen and will collect longitudinal routine clinical data from pediatric and adult patients receiving MC4R agonist therapy according to approved indications.

The goal of this first in human study is to evaluate the preliminary safety and tolerability of AXV-101 in participants with BBS1. The main questions it aims to answer are: * Is AXV-101 safe and tolerable to use in participants with BBS1? * To determine the therapeutic dose of AXV-101 in participants with BBS1 * To investigate the concentration of AXV-101 in blood, urine and tears (both eyes) Participants will undergo comprehensive ophthalmic assessments to evaluate functional and structural changes from baseline to one year in the treated eye compared with the untreated eye. Additional evaluations will include blood, urine, and tear testing for safety and pharmacokinetics, and quality of life questionnaires completed by both participants and caregivers. Safety will also be assessed by monitoring the frequency and severity of adverse events, including serious adverse events, through medical history, physical examinations, and laboratory testing.

Summary of the Study This clinical trial evaluates a novel peptide-based therapy for treating retinal dystrophies, age-related macular degeneration (AMD), and diabetic retinopathy (DR). The therapy consists of peptides derived from fetal tissues, mesenchymal stem cells (MSCs), and bioactive growth factors, administered sublingually for systemic absorption. Study Objectives: Primary Objectives: Assess safety and tolerability, and evaluate the therapy's effects on retinal function and structure. Secondary Objectives: Explore improvements in visual acuity, retinal thickness, vascular health, and disease biomarkers. Study Design: Type: Open-label, single-arm interventional study. Duration: 12 months. Participants: 150 adults, divided into three cohorts: Retinal dystrophies. AMD (dry and wet forms). DR (moderate NPDR and PDR). Intervention: A sublingual solution containing peptides and growth factors, taken 4 times daily. Outcome Measures: Primary Outcomes: Safety (adverse events) and tolerability (treatment adherence). Secondary Outcomes: Functional: Visual acuity and field sensitivity improvements. Structural: Retinal thickness and vascular health. Biomarkers: Serum VEGF, oxidative stress, and inflammatory markers. Study Procedures: Monthly follow-ups for safety monitoring, vision tests, retinal imaging (OCT, FA), and blood biomarker analysis. Comprehensive evaluations at baseline, 6 months, and 12 months. Significance: The study aims to provide an innovative, non-invasive treatment for debilitating retinal conditions, potentially improving vision and retinal health through systemic therapy.

This is an investigator-initiated, prospective, single-center, open-label, single ascending dose clinical study. The study aims to evaluate the safety, tolerability, and potential efficacy of intravitreal injection of IGT001 in patients with retinitis pigmentosa across different dose groups. IGT001 is administered as a single intravitreal injection in the study eye under local anesthesia. Participants will be discharged on the day of treatment, provided that their visual acuity and intraocular pressure are close to baseline levels, and no clinically significant abnormalities in vital signs are observed compared to pre-injection values. The decision for discharge will be determined by the investigator's assessment.

The purpose of the 081-101 study is to evaluate the safety and tolerability of a single subretinal injection of AAVB-081 in USH1B patients with retinitis pigmentosa due to a mutation in the MYO7A gene. The study will also assess the initial efficacy following AAVB-081 administration.

The aim of this clinical trials is to evaluate the safety and efficacy of intravitreal injection of GMP-compliant BM-MSC-derived sEVs in patients with retinitis pigmentosa.

InsightRP2 is a secure online patient registry specific to RP2-associated retinitis pigmentosa (RP). It is our goal to further the scientific understanding of this rare disease and to support research in to a gene therapy for RP2-associated RP. We collect medical, genetic and imaging data from people affected by RP2-associated RP and will coduct a natural history study as well as image analysis studies.

This is natural history study of rods and cones degenerations in patients with Retinitis Pigmentosa (RP) caused by pathogenic mutations in RHO, PDE6a or PDE6b gene mutations.

The aim of this study is an explorative prospective observation of retinal ganglion cell degeneration and/or inner retina degeneration in Retinitis pigmentosa patients. The rate and patterns of progression will be correlated to the outer retina layers as well as clinical and genetic data of patients. Secondary goal is to determine potential parameters for optogenetic treatment eligibility.

This is a multicenter, double-blind, randomized controlled clinical trial to get high - level evidence on minocycline's efficacy and safety（100mg/d, 200mg/d) for Retinitis pigmentosa and to find the optimal treatment dose.

The purpose of this study is to establish the natural history of of participants with BESTROPHIN 1 Vitelliform Macular Dystrophy. The blinding disorder Best Vitelliform Macular Dystrophy (VMD) is caused by any one of more than 250 different mutations in the BEST1 gene. As new treatments are developed, a clear understanding of the natural history of disease progression of BEST1 VMD is necessary. The goals of this natural history study are to: 1. Report the natural history of retinal degeneration in participants with a clinical diagnosis of VMD with molecular confirmation of a pathogenic BEST1 mutation(s). 2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials for the treatment of BESTROPHIN 1 VMD. 3. Compare progression of the identified structural and functional measures between the two eyes to judge the suitability of the second untreated eye as a control for a future clinical trial involving unilateral treatment 4. Identify well-defined patient populations for future clinical trials of investigative treatments for BEST1 VMD.

Introduction Retinitis pigmentosa (RP) is the most common form of genetic retinal degenerative disease. The disease is progressive and leads to blindness and permanent disability within a few years of diagnosis. The etiology of RP is multifactorial. It combines genetic (multiple inheritance patterns) and environmental factors, which makes it difficult to develop effective causal therapy. Many potential methods of RP treatment have been described so far, but the lack of unequivocal evidence of the therapeutic effectiveness of these methods implies a lack of RP therapy standards. Few analyzes have shown that the use of a red subthreshold micropulse laser (SML) with a wavelength of 810 nm causes a neurostimulatory effect on the retina. The subsequent introduction of a yellow laser with a wavelength of 577 nm, dedicated to edema and ischemic retinal diseases, re-initiated a series of questions about the effectiveness of both therapies and the treatment protocols used. This fact emphasizes the need for further verification and optimization of SML treatment regimens in Poland, which has a chance to become a new, widely available, non-invasive standard of treatment independent of the genetic pattern. The aim of the project The main goal of the experiment is to verify the effectiveness of SML and determine the optimal treatment protocol for SML based on a detailed analysis of molecular changes of selected pro-inflammatory, neurotrophic and angiogenic factors (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL- 6 IL-8, IL-10, IL-12 p70, IL-13, IL-17A, CXCL8 / IL-8, MCP-1 / CCL2, MIP-1α / CCL3, MIP-1β / CCL4, IL-8 / CXCL8, CCL5 / RANTES, IP-10 / CXCL10, GM-CSF, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, BMP-4, BMP-7, BMP - 9, TIMP-1, t-PA, PAI-1, NGF, EGF, TNF-α, TGF-β1, TGF-β2, FGF, EGF, G-CSF, GM-CSF, HGF, PDGF-AA, PDGF- AB / BB, VEGF, PAI-1, COL1A1, TSP-2, IFN-γ, N-cadherin, E-selection and P-selection) in tears and peripheral blood of patients with RP. Moreover, the project aims to personalize the assessed treatment regimens by determining the correlation between these changes and the genotype and dynamics of functional changes of the retina in the eyes from the RP subjected to single stimulation with yellow and red SML. Materials and methods The study group will consist of 60 adult patients with retinitis pigmentosa diagnosed on the basis of a characteristic clinical picture confirmed by genome analysis using the whole exome sequencing method and full-field electroretinoography (ERG). In randomized selection, one eye of each patient will be randomly assigned to be stimulated with red (30 eyes) or yellow (30 eyes) SML, and second eye will be assigned to the sham procedure. This will ensure a comprehensive comparative assessment of the effectiveness of both types of SML against each other and against a placebo. The tear film will be collected by wetting the Schirmer strips placed under the lower eyelid before SML (T0) and 28 days (T1), 3 months (T2) and 6 months (T3) after the laser stimulation. In addition, approximately 7.5 ml of peripheral venous blood will be collected at corresponding time points. The assessment of the dynamics of functional changes based on the measurements of the best corrected visual acuity for distance and near vision, contrast sensitivity, microperimetry, 10-2 and 30-2 static perimetry, electroretinogram stimulated with the pattern (PERG) and multifocal electroretinogram (mfERG) in both eyes will be carried out at the time points T0, T1-T3. In addition, during the T0-T3 visits, the morphology of the eyeball, i.e. examination of the anterior segment and fundus of the eye in a slit lamp, examination of optical coherence tomography of the macula and ultrasound of the eyeball will be assessed. The quality of life of the participants of the experiment will be assessed on the basis of the standardized NEI VFQ-25 questionnaire. The quality of life assessment will take place both before the implementation of the SML and during subsequent follow-up visits. Expected project benefits Conducting the proposed experiment will result in verification of the effectiveness of the retinal stimulation by the yellow SML in comparison to the red SML in the eyes with retinitis pigmentosa. In addition, conducting genome analysis and monitoring changes in the concentration of pro-inflammatory, neurotrophic and angiogenic factors in the tear film and peripheral blood in combination with a detailed assessment of the dynamics of functional changes in the eyes with RP after stimulation with an immunomodulatory stimulus SML will enable optimization and personalization of this treatment method in relation to the genetic profile of the patient with RP. The expected results may direct further research on the search for an effective therapy for patients with RP or constitute the basis for the introduction of the world's first standard of adjuvant treatment in this disease entity.

The investigator is examining the safety of transplanting cells into the subretinal space of patients with Retinitis Pigmentosa (RP). The cells are called neural progenitor cells, which are a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, which is a type of neuronal cell. The cells are called "CNS10-NPC." The investigational treatment has been tested in animals, but it has not yet been tested in people. In this study, the investigators want to learn if CNS10-NPC cells are safe to transplant into the subretinal space of people.

The objective of the study is to evaluate: 1. Safety of AuTNA I for subretinal implantation in patients with retinitis pigmentosa; 2. Efficacy of AuTNA I for subretinal implantation in patients with retinitis pigmentosa.

The aim of this study is to determine whether 9-cis-beta Caroten rich D. Brdawiil extract is effective in the treatment of retinitis pigmentosa in adolescent patients.

Knowledge of the pathogenesis of ocular conditions, a leading cause of blindness, has benefited greatly from recent advances in ophthalmic imaging. However, current clinical imaging systems are limited in resolution, speed, or access to certain structures of the eye. The use of a high-resolution imaging system improves the resolution of ophthalmoscopes by several orders of magnitude, allowing the visualization of many microstructures of the eye: photoreceptors, vessels, nerve bundles in the retina, cells and nerves in the cornea. The use of a high-speed acquisition imaging system makes it possible to detect functional measurements such as the speed of blood flow. The combination of data from multiple imaging systems to obtain multimodal information is of great importance for improving the understanding of structural changes in the eye during a disease. The purpose of this project is to observe structures that are not detectable with routinely used systems.

Inherited Retinal Diseases (IRDs) are a heterogeneous group of genetically based degenerative retinal disorders, representing a major cause of visual impairment and blindness in working-age adults. Despite the approval of the first gene therapy for RPE65-related IRD (voretigene neparvovec) in 2017, most IRDs remain untreatable, though many gene therapies are in development. Effective trial design and therapy development require a deep understanding of disease natural history and genotype-phenotype correlations. Over 270 IRD-associated genes are known (e.g., ABCA4, USH2A, RPGR, PRPH2, BEST1), each linked to distinct phenotypes and clinical progression. This retrospective study analyzes clinical, functional, and imaging data (Optical Coherence Tomography, Fundus Autofluorescence, Microperimetry) from a large, genetically characterized IRD cohort at the IRCCS Ospedale San Raffaele up to December 31, 2025. The aims are to describe natural history, define genotype-phenotype relationships, and identify structural and functional outcome measures useful for future clinical trial endpoints, supporting personalized prognosis and trial design.

The main retinal diseases, whether or not associated with specific mutations genetic, cause progressive degeneration of vascular retinal structures and not vascular, resulting in decreased visual function. Often, such diseases affect the noblest part of the retina, called macula. Many retinal diseases can be complicated by choroidal neovascularization which causes frequent bleeding and fluid leakage that accumulates in the subretinal and intraretinal spaces. Although the investigators know many details of each disease affecting the retina, very often the correct diagnostic framework can be complicated, given the presence of morphological elements common to the different pathologies. Similarly, predicting the effect of treatment and the patient's outcome is a constant challenge for the ophthalmologists. Most of the current research has been focused on the assessment of vascular alterations localized in the macula. However, growing evidence highlight the importance of peripheral vascular changes on the outcome of retinal diseases. These changes can be detected only be wide field OCT devices. On the other hand, ocular inflammation and hyperemia represent major assessments in anterior segment disorders, such as dry eye disease. The current grading systems of ocular inflammation, redness and hyperemia are characterized by several limitations, thus making these evaluations still mainly confined to the subjective assessment performed by the ophthalmologist. However, the new generation OCT devices may include also an anterior segment module which can reconstruct anterior segment vessels, non-invasively, using the same technology described for retinal diseases. The main goal of the study is to evaluate the diagnostic contribution of a new generation wide field OCTA device in ocular diseases, which has recently received CE marking. In particular, the investigators will evaluate this new generation device both in retinal and anterior segments diseases, testing for common points and differences with the standard of care non-invasive diagnostic devices. Secondary outcomes include the assessment of the correlation between the patient's visual function (visual acuity) and morphological changes (standard of care imaging assessment) highlighted by the wide field OCT device, with particular attention to microstructural differences between major ocular diseases and the possible development of non-invasive biomarkers, useful for the diagnosis and follow-up of such pathologies.

The primary objective of this clinical trial is to evaluate the safety and tolerability of a single intravitreal injection of the gene therapy drug UGX202 in patients with advanced RP. The secondary objective is, to assess the preliminary efficacy of a single intravitreal injection of the gene therapy drug UGX202 in treating patients with advanced RP.

This clinical trial aims to test the safety and feasibility of using a non-invasive ultrasound device to stimulate retinal nerve cells and restore vision in patients with age-related macular degeneration. Previous studies have shown that artificial stimulation, such as electric and optic stimulations, can partially restore vision, but these methods are invasive and pose surgical risks. The study aims to develop a non-invasive method for retinal stimulation. The investigators will follow the FDA guidelines to limit the ultrasound power and adhere to all clinical trial regulations to ensure all participants' safety. The main questions the investigators aim to answer are: * Is using high-frequency ultrasound safe using a wearable device for localized retinal neural activity stimulation? * Does the stimulation through the device restore vision in patients with age-related macular degeneration? Participants in this study will be asked to undergo Optical Coherence Tomography (OCT) scanning before and after the ultrasound stimulation to evaluate the device's safety. Then, they will receive five stimulation-rest cycles and complete a questionnaire to report what they see and how they feel during the device's operation.

A Phase 1/2, Safety and Efficacy Trial of BS01, a Recombinant Adeno-Associated Virus Vector Expressing ChronosFP (AAV2-CAG-ChronosFP) in Patients with Retinitis Pigmentosa

This pilot study is to determine whether it would be safe and feasible to inject CD34+ stem cells from bone marrow into the eye as treatment for patients who are irreversibly blind from various retinal conditions.

The overall goal of this project, co-funded by the Foundation Fighting Blindness and the USHER 1F Collaborative is to characterize the natural history of disease progression in patients with PCDH15 mutations in order to accelerate the development of outcome measures for clinical trials.

This study explores whether adding early nurse-led and psychological support after the diagnosis of retinitis pigmentosa (RP) can improve patient experience and emotional well-being. RP is a rare, progressive eye disease often diagnosed after a long and difficult process, and receiving the diagnosis can be emotionally distressing. Eighty newly diagnosed adults will be randomly assigned to either usual care or an enhanced pathway that includes early follow-up with a nurse, structured emotional monitoring, and a psychologist visit at six months. The study aims to determine if this structured support improves patient satisfaction and reduces anxiety and depression compared with standard care.

A Phase 1, open-label, non-randomized, dose-escalation study, where approximately 18 eligible patients with retinitis pigmentosa or choroideremia will be enrolled sequentially in up to 4 dose cohorts of RTx-015. Enrolled patients will receive a single, unilateral intravitreal injection of RTx-015 in the study eye at Visit 3 (Day 0) and be followed for a total of 5 years.

The study will perform to follow-up UC-MSCs and CM transplantation. 18 patients will be called back to be examined after 5 years of UC-MSC and/or CM transplantation.

The study will perform UC-MSCs and CM transplantation. There are two groups with different dosages. The first group will be transplanted with 1.5 million cells, meanwhile, the second group is 5 million cells. Each group consists of 30 subjects. All groups will be transplanted via the peribulbar route. All groups will be observed until six months.

Measures of vision in RP patients receiving promising therapy using transcorneal electrical stimulation.

The natural history in individuals with severe retinitis pigmentosa (RP) is variable and there remains an unmet need to better understand disease progression in this population. The goal of this study is to determine which visual assessments individuals with RP and low visual acuity can reliably perform and to evaluate the annual decline of visual function in severe RP.

The objective of this study is to evaluate the safety and tolerability of escalating doses of a gene therapy called GS030-DP (injected study treatment) administered via a single intravitreal injection and repeated light stimulation using a medical device called GS030-MD (stimulating glasses) in subjects with documented diagnosis of non-syndromic Retinitis Pigmentosa

The Vision Research and Assessment Institute (VRAI) was established with the purpose of serving as a testing facility for efficacy endpoints for patients with Low Vision. The mission of the VRAI is to enable the highest quality, standardized efficacy testing of patients with visual impairment. The VRAI facilitates the development and refinement of existing endpoints specifically for testing patients with Low Vision.

This is zM-02's safety, tOlerability, and efficacy in retinitis pigmentOsa first-in-humaN study (MOON). This trial is meant to evaluate the safety and efficacy of ZM-02 in Retinitis pigmentosa (RP) patients. Unilateral intravitreal injections (IVT) will be given into the subject's Study Eye.

This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501/laruparetigene zovaparvovec )) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

The purpose of this study is to characterize the natural history through temporal systemic evaluation of subjects identified with PRPF31 mutation-associated retinal dystrophy, also called retinitis pigmentosa type 11, or RP11. Assessments will be completed to measure and evaluate structural and functional visual changes including those impacting patient quality of life associated with this inherited retinal condition and observing how these changes evolve over time.

This is a Phase 1/2, multi-center, randomized, sham-controlled, dose-escalation study evaluating ZM-02 in patients with advanced retinitis pigmentosa (RP).

The Goal of this study is to evaluate the safety, tolerability, and clinical responses following single dose of DSP-3077. Study enrolls both male and female patients in 3 cohorts with each cohort defined by visual acuity (VA) criteria and dose level of DSP-3077. Each cohort will include 4 participants.

This is a self-controlled randomized clinical trial to investigate the effect of capsular tension ring (CTR) implantation on intraocular lens (IOL) position in cataract patients with retinitis pigmentosa(RP). Each patient will receive CTR implantation in one eye, with the fellow eye serving as control. Postoperative outcomes, including visual acuity, IOL position, and postoperative complications will be compared between eyes.

This natural history study of patients with EYS mutations from Russia and former CIS (Commonwealth of Independent States) territories will accelerate the development of outcome measures for clinical trials. Sensitive, reliable outcome measures of retinal degeneration will greatly facilitate development of treatments for retinitis pigmentosa due to EYS mutations. This approach helps to develop experimental treatment protocol, and assessing its effectiveness. The goals and expected impact of this natural history study are to: 1. Describe the natural history of retinal degeneration in patients with biallelic mutations in EYS gene in Russia and former CIS territories. 2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration in Russia and former CIS territories. 3. Identify well-defined subpopulations for future clinical trials of investigative treatments for EYS-related retinal degeneration in Russia and former CIS territories.

Retinitis pigmentosa and similar degenerative diseases of the retina lead to progressive loss of vision. TES therapy with the CE-marked OkuStim® System is a treatment approved in the EU for slowing the progression of the disease. Patients increasingly report short-term subjective improvements in vision, which have not yet been systematically investigated. This exploratory study is conducted to determine whether these subjective short-term effects can be measured, and therefore also be quantified, by objective tests.

Studying the morphology and function of the normal and diseased retina in vivo is needed for advancing the detection, diagnosis, and treatment of retinal disease. This protocol uses an adaptive optics scanning laser ophthalmoscope (AOSLO) to image the normal and diseased retina with individual cellular resolution non-invasively. The primary objective of this study is to obtain and analyze high-resolution images of the retina, in particular by imaging the cone photoreceptor mosaic, the retinal vasculature and other retinal layers. The study design will involve case-control studies, where cases are followed over time. Subjects age 7 and older may be invited to participate. The main research procedure involves retinal imaging with the AOSLO. The primary endpoint is the observation of differences in retinal images between subjects with and without retinal diseases. These changes will be quantified by examining the cell density, size, spacing and regularity of the cone photoreceptor mosaic, as well as examining the differences between other retinal layers.

The aim of the study is to apply a novel clinical investigation protocol in patients with Phosphodiesterase 6A (PDE6A), PDE6B and Rhodopsin (RHO)-based retinitis pigmentosa. This novel, multimodal clinical examination protocol describes and correlates structural, functional and metabolic aspects during natural disease development. Test-retest variability of new measurements as well as correlations of the structural, functional, and metabolic changes will be defined to be able to define well-suited readouts for safety and efficacy of future treatment developments before they reach the clinical phase.

The objective of the study is to collect adaptive optics (AO) retinal images from human subjects with outer retinal diseases (diseases of the outer retina including photoreceptor, retinal pigment epithelium (RPE), basement membrane or choroidal pathologies) to develop new diagnostic methods, biomarkers, and clinical endpoints.

This is a two-step, multicenter, Phase I/II study including an open-label dose-escalation phase (Step 1) and a three-arm, controlled, double-masked, randomized extension phase (Step 2), in subjects with advanced RCD due to a mutation in the RHO, PDE6A, or PDE6B gene (Step 1), or in any RCD-causative gene (Step 2).

The goal of this clinical trial is to evaluate a specific antisense oligonucleotide medication in one patient with posterior column ataxia with retinitis pigmentosa. The main question it aims to answer is: what is the safety and tolerability of this medication in a single participant.

This is a Phase 1/2 repeat-dose, open-label, two-arm, parallel group safety and efficacy study of two doses of VP-001 (30 μg and 75 μg) in participants with confirmed PRPF31 mutation-associated retinal dystrophy, including participants previously treated with VP001 in the PLATYPUS Study or WALLABY Study for a minimum of 8 weeks.

The purpose of this study is to determine whether the structure and function of the human retina can be studied with high resolution in patients with inherited retinal degenerations using the Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO).

Retinitis pigmentosa (RP) is an inherited retinal degeneration caused by one of several mistakes in the genetic code. Such mistakes are called mutations. The mutations cause degeneration of rod photoreceptors which are responsible for vision in dim illumination resulting in night blindness. After rod photoreceptors are eliminated, gradual degeneration of cone photoreceptors occurs resulting in gradual constriction of side vision that eventually causes tunnel vision. Oxidative stress contributes to cone degeneration. N-acetylcysteine (NAC) reduces oxidative stress and in animal models of RP it slowed cone degeneration. In a phase I clinical trial in patients with RP, NAC taken by month for 6 months caused some small improvements in two different vision tests suggesting that long-term administration of NAC might slow cone degeneration in RP. NAC Attack is a clinical trial being conducted at many institutions in the US, Canada, and Europe designed to determine if taking NAC for several years provides benefit in patients with RP.

This trial employs a single-arm, open-label seamless Phase I/II design, consisting of two stages: Phase I dose exploration and Phase II dose expansion.The primary objective of this trial is to evaluate the safety, tolerability, and efficacy of subretinal injection of ZVS203e solution.

The goal of the study is to investigate the safety, tolerability and efficacy of up to 3 doses of KIO-301 administered by intravitreal (IVT) injection bilaterally every 6 weeks in patients with late-stage retinitis pigmentosa (RP). Late-stage RP patients will include those patients with No Light Perception (NLP), or Low Vision (LV).

The purpose of this Phase 2 Study is to see if the investigational study drug, laruparetigene zovaparvovec, also known as AGTC-501, given in both eyes, is safe and works to preserve and/or improve vision and other symptoms of XLRP.

This study will evaluate the use of autologous bone marrow derived stem cells (BMSC) for the treatment of retinal and optic nerve damage or disease.

The goal of this clinical trial is to learn if NPI-001 works to prevent progression of retinitis pigmentosa in adults diagnosed with Usher syndrome. It will also provide information about the safety of NPI-001. The main questions it aims to answer are: Does NPI-001 slow down the loss of photoreceptors? What medical problems do participants have when taking NPI-001? Researchers will compare NPI-001 to a placebo (a look-alike substance that contains no drug) to see if NPI-001 works to preserve vision. Participants will: Take NPI-001 or a placebo twice a day, every day for 24 months Visit the clinic 9 times for checkups and tests

his prospective, comparative pilot study investigates the safety and functional outcomes of subtenon autologous platelet-rich plasma (PRP) in patients with Retinitis Pigmentosa (RP) and Extensive Macular Atrophy with Pseudodrusen-like Appearance (EMAP). Participants will receive three subtenon injections of autologous platelet-rich plasma (1.5 mL per injection) administered at two-month intervals (M0, M2, M4). The primary objective is to assess functional changes over a 6-month period, with a focus on visual field preservation, evaluated by the Field Preservation Deviation Index (FPDI) and Mean Deviation (MD), as well as best-corrected visual acuity (BCVA, LogMAR). Secondary outcomes include changes in 30-Hz flicker electroretinography (ERG) amplitude, structural retinal parameters on optical coherence tomography (OCT)-including central macular thickness and ellipsoid zone length-and ocular safety outcomes, such as intraocular pressure, local tolerability, and the occurrence of inflammatory or adverse events related to subtenon PRP administration.

This project intends to transplant a clinical level human embryonic stem cells derived retinal pigment epithelium into subretinal space to treat eetinitis pigmentosa(RP) diseases. Through the statistical analysis EDTRS, BCVA, OCT, ERG, Fluorescein angiography, Ophthalmic AB ultrasound changes between before and after the treatment to assess the efficacy and safety 0f RPE transplants to treat RP disease.

The purpose of this Phase 2b study is to evaluate the safety and tolerability of ultevursen administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene. This is a multicenter Double-masked, Randomized, Sham-controlled study which will enroll 81 subjects.

The goal of this clinical trial is to learn if a natural supplement called 9-cis beta-carotene (derived from the Dunaliella alga) can improve vision and retinal function in adults with Retinitis Pigmentosa. The study will also monitor the safety of the food supplement and how it affects levels of Vitamin A-related proteins in the blood. The main questions the study aims to answer are: (1) Does taking the supplement improve light sensitivity in the retina (measured by microperimetry)? (2) Does the supplement improve electrical responses in the eye (ERG) or other visual functions like contrast and color vision? (3) How do blood levels of beta-carotene and Vitamin A change during treatment? Researchers will use a crossover design. This means every participant will receive both the active supplement and a placebo (a "dummy" pill with corn oil) at different times during the study to compare the results. Participants will take two soft-gel capsules twice a day for 3 months, undergo a 6-month "washout" period where no study capsules are taken.Then they will take the opposite capsules (either the supplement or the placebo) for another 3 months. The participants will visit the clinic 4 times over the course of 12 months for eye exams, eye imaging (like OCT), and blood tests. Participants will also receive follow-up phone calls every 6 weeks to check on their progress and health.

This study evaluates the safety of a single injection of jCell (famzeretcel) comprising 6.0 million (6.0M) retinal progenitor cells over a six-month study period in a cohort of adult subjects with RP. Additionally, changes in visual function will be evaluated at six months between the active treatment group (6.0M jCell) compared to sham-treated controls.

This is a Phase 1/2 Study to Assess the Safety and Efficacy of OCU400 in patients with retinitis pigmentosa associated with NR2E3 and RHO mutations and in patients with LCA due to mutation(s) in CEP290 gene (OCU400-101). To document prospective eye pathology in the above subjects Investigators will also conduct a Natural History Study (OCU400-104)i This is a multicenter study, which will be conducted in two phases and will enroll up to a total of 24 subjects in the OCU400-101 and 100 subjects in the OCU400-104 study.

This is a Phase 3 study to Assess the Efficacy, Safety and Tolerability of OCU400 in patients with retinitis pigmentosa (RP) associated with RHO mutations and patients with any other RP associated mutation with a clinical phenotype of RP. This is a multicenter, assessor blinded and randomized study which will enroll 140 subjects. Study has completed enrollment of all 140 subjects.

Retinitis Pigmentosa (RP) is a devastating eye disease and at present there are no known treatment options that can alter the rate of vision loss and eventual blindness. In a series of studies in animal models, the effects of exposing cones in the periphery of the retina to a large excess of oxygen results in progressive oxidative damage to cone photoreceptors and cone cell death. Cone cell death gradually spreads from the periphery of the retina toward its center, narrowing the visual field and eventually resulting in tunnel vision. Compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione ratio (GSH/GSSG) in aqueous humor and a significant increase in protein carbonyl content. This demonstration of oxidative stress and oxidative damage in the eyes of patients with RP, suggests that oxidative damage-induced cone cell death in animal models of RP may translate to humans with RP and support the hypotheses that (1) potent antioxidants will promote cone survival and function in patients with RP and (2) aqueous GSH/GSSG ratio and carbonyl content on proteins provide useful biomarkers of disease activity in this patient population. Orally administered N-acetylcysteine (NAC) has been found to be a particularly effective antioxidant that promotes prolonged cone survival and maintenance of cone function in a mouse model of RP. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, there is good rationale to test the effect of NAC in patients with RP. Oxidative damage has been implicated in several diseases including cystic fibrosis, chronic obstructive pulmonary disease (COPD), and Idiopathic Pulmonary Fibrosis. The effect of oral NAC has been tested in these indications in several clinical trials providing extensive safety data. In COPD, NAC 600mg bid improves airway function and reduces the frequency of acute exacerbations. Doses of up to 1800mg/day have been well-tolerated in the treatment of Idiopathic Pulmonary Fibrosis. Paracetamol (acetaminophen) toxicity is treated with a loading dose of 140 mg/kg NAC followed by 70 mg/kg every 4 hours for 17 doses. Normal volunteers tolerated a dose of 11.2 grams NAC/day for three months without any serious undesirable effects and in another study a dose of 500mg/kg/day was tolerated. The most frequent adverse events associated with the oral administration of NAC are gastrointestinal in nature and include vomiting, diarrhea, stomatitis, abdominal pain and nausea (incidence rate \>1/1000 to \<1/100). Hypersensitivity reactions including anaphylactic shock and anaphylactic/anaphylactoid reaction (incidence rate \<1/10,000), dyspnea, bronchospasm (incidence rate \>1/10,000 to \<1/1000), angioedema, tachycardia, urticaria, rash and pruritus (incidence rate \>1/1000 to \<1/100) have been reported less frequently. Finally, reports of headache, tinnitus, pyrexia, blood pressure decreased (incidence rate \>1/1000 to \<1/100), face edema and hemorrhage have also been collected with oral NAC. In the FIGHT-RP 1 Study, the investigators used escalating doses of NAC effervescent tablets (from 600 mg in Cohort 1 to 1800 mg in Cohort 3). The maximum tolerated dose was 1800 mg twice a day which will be continued in this study.