Coats' Disease

The purpose of this project is to capture research images from microscope integrated Optical Coherence Tomography (MIOCT) integrated into a Zeiss Artevo 800 surgical microscope with an add-on investigational 3D OCT scanner (hereafter called the 4D MIOCT) in participants undergoing clinically-indicated surgical procedures for a range of ocular diseases. The researchers will evaluate normal and abnormal microanatomy of the eye, image during surgical procedures, and track subretinal injections for therapeutic delivery during surgery (volumes measured/analyzed from the OCT images after surgery). This study is an observational imaging study with no treatment interventions for research purposes. The population is 5 adult ophthalmic surgical patients scheduled for eye surgery at Duke Eye Center, Durham. Up to 8 patients may be enrolled due to potential for surgery scheduling changes that would not allow research imaging on a surgery day for up to 3 patients. Research activities consist of investigational 4D MIOCT integrated into Zeiss Artevo 800 imaging of the eyes during surgery and collection of clinical data and other imaging from the participant's medical record, clinical visit and surgical procedure. Additional imaging of the participant's eye performed for clinical care will be extracted from the medical record for comparison to the intraoperative images. In this initial pilot, comparisons will enable design of future studies for accuracy, precision and reproducibility of the research device in eye surgery. For study participants there is no additional risk to the participant beyond what is normal for their ophthalmic surgery. No medications or surgical interventions/activities will be performed for research purposes. Images will be captured during the standard care ophthalmic microsurgery. This research will utilize the data gathered during OCT imaging performed as described above. The data collected from the OCT systems will be analyzed offline to allow for image processing and alternate visualizations of the area under study. The data gathered from 4D MIOCT imaging will be compared to existing clinical studies (performed as part of standard of care) on the participant, should they exist, for the purpose of identifying whether new information is gained by 4D MIOCT. Researchers will review the participant's Medical Record for up to three eye care visits prior to surgery and record information related to ocular health, eye examinations and imaging and prior ophthalmic treatment. No additional clinical studies will be performed for the purpose of this study.

This is a randomized, double-blind, parallel study that will be conducted in patients with Diabetic Macular Edema (DME) to assess efficacy and safety between test and reference products. Total 70 subjects with DME are planned to be randomized into this study. Enrolled subjects will receive total 3 doses of 0.5 mg Intravitreal injection of either test or reference product once every 4 Weeks (Day 0, Week 4±3 days and Week 8±3 days). All subjects will have their first injection of ranibizumab on Day 0 and undergo a safety visit 48hrs after the first injection. At subsequent visits, the subject will have a safety follow up prior to each intravitreal injection. Also the subject will have a safety follow up visit 48hrs after second and third injection. The final visit or end of study visit will be on Week 12±3 days for efficacy and safety evaluation.

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.

BACKGROUNDS Nowadays, phacoemulsification for cataract treatment is the most common surgical procedure performed and anesthetics procedure has been shifted from retrobulbar or peribulbar anesthesia to topical anesthesia (TA). Phacoemulsification under TA proved to be a safe and low risk procedure with the incidence of adverse events requiring medical emergency team interventions to be 0.04%. However, it is not uncommon that patients can suffer from pain, anxiety and unpleasant visual sensation during this procedure. Complementary sedation has long been thought to alleviate the anxiety and pain of the patient during surgery with local anesthesia. Studies revealed that approximately one fourth of the patients underwent phacoemulsification under TA or retrobulbar anesthesia requested additional intravenous sedation of midazolam. \[8\] However, the intravenous sedation, such as midazolam, propofol, or etomidate, increase the risk of additional anesthetic complications of heart rate, blood pressure, body temperature, and nausea, \[9,10\] and therefore, anesthesia monitoring was mandatory during the surgery. Compared with intravenous sedation, oral sedation is less costly and less invasive. Studies with different oral sedation agents revealed different effects. In the study of 41 patients serving themselves as control, patients reported more pain and photophobia in the surgery with TA alone than the other with midazolam syrup and oral transmucosal fentanyl citrate. However, two studies comparing oral diazepam or triazolam with intravenous midazolam showed similar rates of anxiety and pain or noninferior satisfaction. Moreover, the randomized control trial containing 50 procedures in each groups revealed that patients received TA alone during phacoemulsification reported similar pain or anxiety level to those received complementary intravenous midazolam. Despite the abundant results from above, nearly 40% patients reported moderate to extremely anxiety during phacoemulsification under TA, and approximate 7% of patients rated themselves extreme anxiety or were diagnosed as anxiety. A simple comparison between with or without complementary sedation for general patients underwent phacoemulsification with TA is merely not enough. Further investigations to reduce the anxiety experienced during phacoemulsification with TA according to patients' characteristics is therefore mandatory. Previous studies had showed that patients with higher level of trait anxiety reported higher anxiety response for a stressful situation. Preoperative anxiety levels were also reported to be a significant predictor of pain experience during phacoemulsification with TA. The need for complementary sedation could be different in patients with different trait anxiety. Furthermore, different severity levels of anxiety and pain were experienced during the first and second eye surgery. Therefore, in this study, the investigators will investigate the trait anxiety of patients planned for phacoemulsification under TA and its effect on their anesthetic satisfaction with complementary oral sedation. The investigators will also analysis the anxiety and pain experienced in the first and second eye phacoemulsification in patients with different levels of trait anxiety. The investigators choose alprazolam as the oral sedative. It was reported to have a shorter half-life and less side effects of drowsiness and lightheadedness than diazepam used in previous studies.

The AnovaOS™ Network Powered Patient Registry may be used to inform the development and conduct of clinical trials and observational studies designed to better understand, prevent, diagnose, treat, ameliorate or cure disease. The AnovaOS™ Network Powered Patient Registry may additionally be used to expedite identification and recruitment of participants for clinical trials of promising therapeutics and observational studies.

The MRI perfusion imaging using arterial spin labeling (ASL)'s non-invasive technique (i.e. without injection of contrast medium) allows, thanks to recent technological improvement of the spatial resolution, measuring several perfusion parameter of the retinal tissue such as the regional Blood Flow (rBF) or the cerebral blood flow (cBF) expressed in ml/100g/min. Reliable application of ASL thus requires the precision and specificity of the MRI protocol to be tested.

This study will establish a repository of biospecimens to generate induced pluripotent stem (iPS) cells, which will be used to determine molecular mechanisms for potentially blinding eye diseases including but not limited to: Best Vitelliform Dystrophy (Best Disease); Late-Onset Retinal Degeneration (L-ORD); Age-Related Macular Degeneration (AMD); Leber congenital amaurosis (LCA); Joubert syndrome; X-linked retinitis pigmentosa (RP); oculocutaneous albinism; Stargardt s with ABCA4 gene mutations; Waardenburg syndrome, coloboma, Enhanced S-Cone syndrome (ESCS), Spinocerebellar Ataxia, Type 7 (SCA7) and eye diseases associated with MITF, PAX2, or PAX6 gene mutations. Skin fibroblasts, saliva, hair keratinocytes, urine, and/or blood cells may be collected from participants with retinal diseases and from age, sex and ethnicity-matched healthy participants. Although research involving multiple different ocular cell types from these patients may be performed, the vast majority of the work will be centered on the retinal pigment epithelium (RPE) and neural retina. RPE and/or neural retinal cells generated from the iPS cells of participants with retinal diseases and healthy volunteers will be used to analyze molecular mechanisms involved in disease initiation and progression. In addition, the iPS cell-derived ocular cells will be used to perform high throughput (HTP) drug screens aimed at suppressing the molecular phenotypes of the disease and to identify potential therapeutic agents for these diseases. Objectives: The primary objective of this study is to generate participant-iPS cells that can be differentiated into ocular cell types, to be used to study the molecular mechanisms of and to develop treatments for ocular conditions. This objective will be carried out in three phases. First, this study will establish a repository of fibroblasts, keratinocytes, urine-derived cells and/or blood cells collected from participants with eye diseases and from matched controls without any eye diseases. Second, the somatic cell repository will be used to generate iPS cells, which will be differentiated into RPE, neural retinal and/or other ocular cells. These cells will be used to elucidate molecular pathways that have led to disease pathogenesis. In the third phase, the participant-specific ocular cells will be used to perform high throughput drug screens to identify novel potential therapeutic compounds. The cells obtained in this protocol may be genetically modified, may be transplanted into animals in the laboratory, and, if used in the development of cell-based therapies, may be transplanted into humans. Transplantation into humans will be done as a part of a different study. Study Population: We plan to recruit 465 participants with ocular conditions including but not limited to: degenerative retinal diseases, optic atrophy, microphthalmia/anophthalmia, ciliopathy, and other ocular developmental or degenerative conditions, and 465 healthy volunteers without any eye disease. If possible, unaffected siblings and relatives of participants with eye diseases will be included as healthy volunteers. Design: In this basic science, research-oriented study, skin, saliva, hair, urine, and/or blood samples may be collected from affected participants with the eye diseases and/or genetic mutations under study, and from control participants matched for age, sex, and ethnicity. The sample collection procedures will incur only minimal risk to adult participants. This study will typically require only one visit by each participant. Participants may be requested to return if their initial sample(s) did not produce adequate cells for study in the laboratory. Participants who were previously enrolled to provide samples for research-grade iPS cell generation may return for an additional visit to provide samples for clinical-grade iPS cell generation, if eligible. The skin fibroblast, keratinocyte, urine-derived cells and/or blood samples will then be used to generate participant-specific iPS cells, and these cells will then be differentiated into RPE, neural retinal and/or other ocular cell types. iPS cells may not be made from all samples. The investigators will use the samples for research studies aimed at identifying molecular and signaling pathways underlying disease onset and progression and for developing potential therapeutic treatments for the eye diseases under study. Outcome Measures: The outcome measures for this study include the creation of iPS cells from at least one of the three types of somatic tissues collected from each participant, the differentiation of iPS cells into RPE, neural retinal cells and/or other ocular cells, and the identification of molecular and physiological phenotypes in these cells that may be linked to the onset or progression of the ocular conditions being studied. This analysis may lead to the discovery of therapeutic interventions for these diseases. There are no specific participant-based clinical outcomes for this protocol. Participants will, in general, be seen only once for this protocol. In rare cases, participants may be requested to return to the clinic if their initial sample(s) did not produce adequate cells for study in the laboratory.

CHOPXE is a single-center, cas-control, cross-sectional study with the objective of comparing choriocapillaris flow deficits by OCT angiography (OCT-A) between healthy control subjects and patients with pseudoxanthoma elasticum. Study rationale Pseudoxanthoma elasticum (PXE) is a rare disorder, affecting between 1 in 25,000 and 1 in 100,000 people. This autosomal recessive disorder is caused by mutations in the ABCC6 gene. Mutations in the ABCC6 gene have been demonstrated to impair cellular efflux of ATP, which is ordinarily converted to inorganic pyrophosphate (PPi) and adenosine. PPi is a potent endogenous inhibitor of calcification, while adenosine contributes indirectly to calcification inhibition by suppressing the synthesis of tissue-nonspecific alkaline phosphatase (TNAP). The disease has been shown to cause ectopic mineralization and fragmentation of tissue elastic fibres. * The initial indications of the disease manifesting in the skin are frequently observed in childhood or adolescence. These initial signs evolve slowly and unpredictably, as evidenced by the appearance of papular skin lesions in flexural zones. * The ophthalmological manifestations (peau d'orange, angioid striae, sub-retinal neovascularization, optic nerve drusen) may be responsible for visual impairment through central blindness. * The presence of vascular manifestations, including peripheral arterial disease, gastrointestinal bleeding and ischaemic stroke, has been identified as a contributing factor to the premature mortality observed in patients with PXE, when compared to the general population. Angers University Hospital is a national rare diseases reference center for PXE, with an active file of nearly 300 patients. At present, there is no treatment available for pseudoxanthoma elasticum, with the exception of treatment for complications. A number of treatments are currently under investigation; however, there is an absence of relevant objective criteria with which to evaluate their efficacy. The wall of the eyeball is composed of three tunics: the sclera, the choroid and the retina. The retina is composed of multiple layers, with the deepest layer being the retinal pigment epithelium (RPE). The choriocapillaris constitutes the most superficial layer of the choroid, providing blood supply to the outer retina and photoreceptors. The existence of a mutual dependence between these two structures has been established; the choriocapillaris requires the regulatory factors (vascular endothelial growth factor inhibitors) secreted by the RPE for its functionality. Conversely, the RPE is dependent on nutrients and oxygen from the systemic circulation via the choriocapillaris bloodstream to supply the photoreceptors. Bruch's membrane is a structure located between the retinal pigment epithelium and the choriocapillaris (between the neuroretina and the systemic circulation), which regulates the exchange of molecules between these tissues. The process of pathological mineralization in pseudoxanthoma elasticum has been demonstrated to induce alterations in the exchange mechanisms between these structures, which may potentially result in the premature degradation of photoreceptors and the choriocapillaris. Optical coherence tomography (OCT) is a widely utilised diagnostic tool in ophthalmology consultations, enabling precise analysis of retinal structures and the optic nerve. This advanced technology boasts a resolution of up to the micrometer, with no need for contact with the eye and a non-invasive procedure. This is an optical ultrasound mode, based on light interferometry. The technology utilises laser reflection from various anatomical structures to facilitate the measurement of retinal thickness. In 2014, a new imaging technology for the retinal and choroidal vascular network was developed from OCT: OCT angiography (OCT-A). The technology is based on the principle of detecting the movements of diffracting particles, such as red blood cells, in sequential OCT B-scans taken at the same point on the retina several times. This makes it possible to objectify the presence of blood vessels. The advent of this new examination has facilitated the analysis of retinal and choroidal vascularization, and in particular retinal and choroidal microcirculation in vivo, such as the choriocapillaris, on a routine clinical basis, which had previously been inaccessible. Consequently, numerous researchers have initiated studies of the choriocapillaris, with a particular focus on the flow deficits of the choriocapillaris. This is due to the fact that the lateral resolution of OCT-A is approximately equivalent to the macular intercapillary distance, thereby precluding direct observation of the vascularization of the choriocapillaris. The choriocapillaris is responsible for relaying the systemic circulation to the outer retina, thereby providing nutrients and oxygen to the photoreceptors. Consequently, impairment to the choriocapillaris could potentially play a pivotal role in the development of numerous retinal pathologies. A first study revealed the presence of choriocapillary flow deficits in patients exhibiting angioid streaks on the fundus, including two patients with PXE. These findings were subsequently corroborated by a subsequent study conducted on 21 patients with PXE in the pre-atrophic stages. These results, if confirmed by further studies on larger samples, could make it possible both to use choriocapillary flow deficits for the early diagnosis of PXE, as an additional diagnostic argument in atypical cases, but also to serve as an objective and relevant biomarker for interventional studies evaluating the efficacy of treatment under development. Patient recruitment The selection of healthy control subjects is made from the database of healthy volunteers at the Clinical Research Centre (CRC) of Angers University Hospital (France), who meet the eligibility criteria. In addition, this study may also be offered to eligible persons waiting for a consultation or accompanying a relative in Angers University Hospital Ophthalmology Department. The planned inclusion period is 1 year. PXE patients whose data will be used for matching have already been recruited as part of routine care. It is anticipated that the study will encompass a total of 60 healthy control subjects and 60 PXE patients. Data collected Following inclusion, participants' characteristics are collected (age, sex, general history, ophthalmological history, cardiovascular events, whether or not digestive bleeding has occurred, and whether antiaggregant or antiplatelet therapy is being taken). The ophthalmological assessment is carried out during a scheduled consultation at the Angers University Hospital Ophthalmology Department. It includes a measurement of best corrected visual acuity, a slit lamp examination, a fundus and an OCT-A scan. These elements enable us to rule out ophthalmological pathology (maculopathy, retinopathy, optic neuropathy, glaucoma). If the quality of the OCT-A signal is unsatisfactory (too much artifact and/or image quality signal less than 50/100), the participant is offered pupillary dilatation if there is no contraindication to dilatation (risk of closure of the iridocorneal angle). Dilatation is performed by instilling tropicamide into both eyes. For PXE patients, additional data of interest (described below) are collected from the patient's medical file. * ABCC6 gene mutations * Presence or absence of disease-specific dermatological changes * Presence or absence of disease-specific ophthalmological changes * Presence or absence of inflammatory skin flares * Presence or absence of arterial stenosis of the lower limbs * Presence or absence of carotid artery dysplasia We also collect patients' age and weight, in order to calculate their body mass index and the presence of cardiovascular risk factors (diabetes, hypertension, smoking, dyslipidemia), as these factors can influence choriocapillary flow deficits, and will enable us to compare the characteristics of patients and controls. For both PXE patients and healthy subjects, we will select a single eye for our study, choosing the eye with the least choriocapillaris flow deficits (lowest mean percentage on 6x6mm sections). The OCT-A choriocapillaris images are exported to Image J software for image processing and calculation of the various parameters of interest (percentage of flow deficit over the entire slice and over the various subsectors).

In the diagnostic approach of patients with ophthalmologic diseases, as well as for surgical purposes, the administration of mydriatic and cycloplegic drugs is indispensable. Among these, the combination of tropicamide and phenylephrine (TF) is commonly used. Studies evaluating the topical ocular administration of these medications have demonstrated an adequate risk-benefit balance; however, certain local and systemic safety aspects remain insufficiently evaluated. Justification: This study will help identify the at-risk population (clinical determinants) prior to the administration of drugs such as TF, provide additional information regarding the safety profile of this drug at the 8 mg/50 mg/mL concentration, and propose measures to reduce the occurrence of adverse drug reactions (ADRs) in at-risk populations. It also aims to develop safety barriers that allow for safer administration of the medication. Moreover, this research provides a first approximation and establishes the basis for future studies that may compare different TF concentrations. Hypothesis: There will be a positive association between clinical determinants and the occurrence of adverse drug reactions. Research Question: Is there an association between the clinical determinants of hospitalized patients and the occurrence of adverse drug reactions following the administration of tropicamide/phenylephrine? Objective: To evaluate the association between clinical determinants and the occurrence of adverse drug reactions in hospitalized patients who received tropicamide/phenylephrine 8 mg/50 mg/mL. Materials and Methods: An ambispective study will be conducted to identify ADRs associated with TF administration, as well as to characterize pathologies that may predispose patients to ADRs (clinical determinants, CD), through the use of a questionnaire, with the purpose of establishing an association between them. Data Analysis: Results will be analyzed using the Chi-square test for qualitative variables and the calculation of odds ratios (OR) with 95% confidence intervals. Quantitative variables will be analyzed using the Student's t-test for normally distributed data, or the Wilcoxon signed-rank test for data not normally distributed. Normality will be assessed with the Kolmogorov-Smirnov test (p \> 0.05). The association between CDs and ADRs will be evaluated through logistic regression analysis

This clinical trial aims to address the scarcity of retinal image datasets in Pakistan by providing a comprehensive digital fundus photograph dataset, accompanied by expert grading. The dataset will encompass retinal images from Pakistani individuals, meticulously labeled by three Vitreo Retinal Specialists. These specialists will assess the presence and severity of common retinal disorders, including No Diabetic Retinopathy (No DR), Mild, Moderate, Severe, Proliferative Diabetic Retinopathy, Clinically Significant Macular Edema (CSME), and Advance diabetic Eye Diseases (ADED). Each image will also be evaluated for diagnostic clarity and the presence of any additional findings. Final grading decisions will be reached through unanimous consensus among the graders, ensuring the dataset's reliability and accuracy. This initiative holds promise for advancing ophthalmic research and improving patient care in Pakistan and beyond.