Leber Hereditary Optic Neuropathy (LHON)

Researchers are investigating the feasibility of producing artificial vision in people who are blind by using a device called the Intracortical Visual Prosthesis (ICVP). This study aims to test the safety of the ICVP system and evaluate whether electrical stimulation of the brain's visual processing areas can create visual percepts. The study involves participants with no light perception or very limited vision who have been blind for at least one year and have a history of normal or near-normal vision in early life. The intervention involves implanting wireless floating microelectrode arrays (WFMAs) into the visual cortex on one side of the brain. These devices deliver wirelessly transmitted electrical stimulation intended to induce artificial vision. Each participant will have multiple WFMA devices implanted. After surgical recovery, participants will undergo weekly testing for one to three years to assess the ability of electrical stimulation to generate visual percepts and evaluate the device's safety and efficacy. Participants will attend regular testing sessions to measure visual perception responses to stimulation and monitor safety outcomes. Researchers will perform assessments from two weeks after surgery through the entire device use period, up to three years. The primary outcome is the safety of the WFMA-based cortical interface, while secondary measures evaluate its effectiveness at producing visual percepts. The study includes video and audio recordings, cognitive and spatial functioning tests, and MRI scans. Participant involvement may last up to three years, with ongoing monitoring throughout the study.

Researchers are evaluating a new handheld optical coherence tomography (OCT) device designed to automatically align with the eye to capture detailed retinal images. This pilot study aims to assess this advanced imaging technology in healthy adult volunteers, adult patients, and pediatric patients with eye and retinal diseases, addressing current challenges in imaging uncooperative patients, especially children. The study is observational and led by Duke University, focusing on improving imaging speed, alignment, and data quality for retinal assessment. The study uses a Swept Source OCT system with enhanced hand-held probe technology that auto-aligns to the patient’s eye and detects image quality in real time, automatically saving optimal images. Participants include 20 healthy adults, 20 adult patients, and 10 pediatric patients from ophthalmology clinics. Imaging will be performed during clinical visits, with up to four single imaging sessions over two years to capture detailed retinal structure and blood flow. Participants will undergo retinal imaging using the handheld OCT device during their clinical visits. Researchers will analyze images for retinal microanatomy abnormalities and retinal thickness at specific eye regions, collecting data securely for further analysis. The study will monitor outcomes over multiple sessions for up to two years, with no known risks reported from prior handheld OCT use. The total participation duration depends on the number of imaging sessions completed within the study timeframe.

Phacoemulsification is a common cataract surgery performed under topical anesthesia, which is generally safe but can cause pain, anxiety, and discomfort for some patients. This research evaluates the effect of oral anti-anxiety medication, specifically Alprazolam, on improving patient satisfaction during second eye cataract surgery. The study aims to clarify whether oral sedation can reduce pain, anxiety, and side effects like nausea and dizziness compared to no sedation during phacoemulsification. Patients will receive either a single oral dose of Alprazolam or a placebo tablet 30 minutes before surgery. The dose of Alprazolam is 0.5 mg for most patients, with a reduced 0.25 mg dose for those over 65 years or with liver disease. The study compares these groups to assess how oral sedation affects anxiety, pain, and surgical satisfaction. This is an extension study involving patients undergoing surgery on their second eye with topical anesthesia. During the trial, participants will complete questionnaires assessing pain, anxiety, and overall satisfaction before and after surgery. Researchers will monitor intraoperative discomfort and postoperative anxiety levels. Data from approximately 250 patients will be collected and analyzed for these outcomes. This study runs from March 2025 to December 2027, focusing on improving cataract surgery experiences safely and conveniently.

Researchers are developing and managing the AnovaOS Network Powered Patient Registry to collect real-world patient data across various diseases globally. This registry aims to capture meaningful clinical information on diagnosis, infection course, treatments, and outcomes to enhance understanding and support future clinical trials and observational studies. The registry serves as a resource to better understand, prevent, diagnose, and treat diverse health conditions. Participants' data will be gathered through this registry, which can also be used to recruit individuals for clinical trials and observational studies on promising therapies. The registry collects ongoing information on patients' health status and treatments, enabling long-term monitoring and analysis. This observational study does not involve administering treatments but focuses on data collection and management. Participants will provide information through questionnaires or instruments, either personally or via an informed proxy, with an expected follow-up once per year. The research team will assess natural history, clinical effectiveness, safety, and quality of care over a period of five years. The registry includes patients with a wide range of conditions, and participation requires informed consent and the ability to complete follow-up data collection.

Researchers are studying inherited eye diseases, including both congenital and age-related conditions, to better understand the genes involved and how these genetic changes affect the eye. The study includes families and individuals from diverse backgrounds who have or are related to someone with inherited eye diseases such as cataracts, corneal dystrophies, retinal degenerations, myopia, and glaucoma. This observational study aims to identify specific genes and the biological processes linked to these eye conditions. Participants will have one visit lasting 3 to 4 hours during which they will undergo a detailed eye exam including pupil dilation, electroretinography, blood tests, and saliva collection for genetic testing. Researchers will analyze genetic material from blood or saliva to find mutations associated with inherited eye diseases. Some participants may also discuss their genetic test results with the study team. During the visit, participants' medical and family histories will be reviewed, and several assessments will be conducted to characterize their eye health. The study measures clinical and genetic features of visual disorders using various genetic and biochemical analyses. Participation involves only one visit, and safety is monitored by excluding those with infections or conditions that mimic inherited eye diseases. The research may continue reviewing genetic data until 2032.

Researchers are studying the relationship between clinical factors and the occurrence of adverse drug reactions in hospitalized patients who receive tropicamide/phenylephrine 8 mg/50 mg/mL. This study aims to identify which clinical determinants may increase the risk of these reactions and provide safety information for this commonly used ophthalmic drug combination. It also seeks to establish safety measures for patients undergoing eye examinations or surgery where these drugs are used. The study involves hospitalized patients scheduled for surgery who will receive two drops of tropicamide/phenylephrine 8 mg/50 mg/mL. Vital signs will be measured before administration and then at several time points afterward, including 5, 15, 30 minutes, and 1, 2, and 3 hours post-administration. Data will be collected using questionnaires and analyzed to find associations between clinical factors and adverse reactions. Participants will be monitored closely through vital sign checks and questionnaires during the study period. Researchers will evaluate adverse drug reactions and clinical determinants to understand their connection. The main outcome is to assess vital signs at set intervals following drug administration and identify any adverse reactions. The study is observational and aims to enhance the safety profile of this medication in hospitalized patients.

Researchers are evaluating a cortical visual prosthesis that uses intracortical microelectrodes to provide a limited but useful sense of vision to people who are profoundly blind. This pilot study aims to gather important information about the safety and effectiveness of this neuroprosthetic device, which may help restore some vision when the communication between the eye and brain is lost due to conditions like glaucoma or optic nerve damage. Visual prostheses offer hope to those with blindness caused by retinal or nerve damage where other treatments have limited success. The study involves implanting the CORTIVIS vision neuroprosthetic system, which uses an FDA-cleared microelectrode array, into blind volunteers through a minimally invasive surgical procedure called a minicraniotomy. The array is placed near the occipital pole or other visual areas of the brain. Researchers will collect feedback on the electrical stimulation that produces visual perceptions and investigate if participants can learn to interpret these signals into meaningful patterns that aid in recognizing and locating objects or navigating environments. Participants will be monitored during the post-surgical period in hospital rooms and psychophysical laboratories. The study will measure thresholds for visual perceptions, map visual phosphenes, assess visual acuity, motion perception, and overall visual function over up to six months. Safety is closely monitored by tracking adverse events. The trial aims to improve quality of life by enabling blind individuals to gain some functional vision through this neuroprosthetic system.

Researchers are evaluating the safety and effectiveness of long-term electrical stimulation using a home-based device for treating open-angle glaucoma, a condition where the optic nerve deteriorates faster than usual regardless of eye pressure. This open-label study focuses on patients who are safe to participate but do not meet the exact criteria for a randomized trial. The goal is to understand how repetitive transorbital alternating current stimulation (rtACS) affects optic neuropathies. Participants will receive active electrical stimulation treatment every other day for eight weeks using a headband device that delivers current to the retina. This treatment period is part of a study designed to monitor changes over time in the visual field and other eye health markers using specialized tests and imaging. Throughout the study, participants will undergo regular assessments including visual field tests (Humphrey Visual Field Index and Mean Deviation), optical coherence tomography for retinal layers, visual acuity tests, and various imaging techniques to evaluate retinal and optic nerve health. These evaluations occur from baseline through six months. The study includes monitoring for safety and effectiveness, with participants involved in scheduled visits and follow-ups to track their progress and any changes in vision.

Researchers are investigating the safety and effectiveness of a gene therapy called NR082 for treating Leber's Hereditary Optic Neuropathy (LHON) caused by a mitochondrial ND4 gene mutation. The study includes two parts: Part 1 is a Phase 1/2 dose-finding study involving adults aged 18 to 75 years to determine a safe and effective dose. Part 2 is a Phase 3 study with a safety run-in phase and a randomized, double-blind, sham-injection controlled trial involving participants aged 12 to 75 years. All participants have vision loss related to LHON with a specific genetic mutation and have had reduced visual acuity for more than 6 months but less than 10 years. In Part 1, participants receive a single intravitreal injection of NR082 at varying doses, starting with 1.5 × 10^9 viral genomes (vg) in 0.05 mL per eye. The Safety Review Committee (SRC) reviews safety data to decide on dose adjustments. Part 2 starts with a safety run-in phase where six subjects, including at least one minor aged 12 to under 18, receive a higher dose of 4.5 × 10^9 vg in 0.05 mL per eye. After at least 6 weeks of monitoring and SRC approval, the study continues with a randomized, double-blind phase comparing NR082 injections to sham injections in one eye. Participants will be monitored through various visits over time to assess safety and vision outcomes. Safety and tolerability are tracked at multiple timepoints up to 12 weeks in Part 1, and up to 52 weeks in Part 2. Researchers will evaluate visual acuity improvements, immune responses, and quality of life changes. Eye examinations, genetic testing, and comprehensive safety assessments will be conducted throughout the study. The total study duration includes initial dose-finding, safety monitoring, and long-term follow-up to understand the effects of NR082 treatment.

Researchers are studying inherited eye diseases to identify the genes involved and understand how symptoms vary among people with similar genetic changes. The study aims to gather detailed genetic information and clinical data to support the development of precise treatment and prevention strategies for vision-threatening conditions. This research is also designed to help establish protocols for specific inherited eye disorders and serve as a referral center for undiagnosed genetic eye diseases. Participants include individuals with known or suspected inherited eye diseases and their unaffected relatives. All participants undergo a medical history review, physical exam, and eye exam, along with blood or saliva sample collection. Some may also provide additional biological samples such as skin biopsies, eye cell samples, tears, urine, saliva, stool, hair, or cheek cells. Various specialized eye tests may be performed, including retina tests, eye movement tests, fluorescein angiography, microperimetry, and color vision assessments. Optional procedures may include MRI and completion of questionnaires. Throughout the study, participants’ clinical data, eye exam results, and biological samples will be collected and analyzed. Outcome measures focus on establishing a study cohort and identifying the best clinical variables to measure treatment effects. The study also aims to reveal related health conditions, collect research samples, and determine the genetic causes of inherited eye diseases. Participation involves ongoing evaluations, with data securely stored and used to support future research. The study is open to participants aged 1 to 120 years and includes both affected individuals and healthy volunteers related to them.