Spontaneously Immortalised Nonhuman Primate Müller Glia Cell Lines as Source to Explore Retinal Reprogramming Mechanisms for Cell Therapies.

Cell replacement therapies for ocular diseases characterised by photoreceptors degeneration are challenging due to poor primary cell survival in culture. A stable retinal cell source to replace lost photoreceptors holds promise. Müller glia cells play a pivotal role in retinal homoeostasis by providing metabolic and structural support to retinal neurons, preventing aberrant photoreceptors migration, and facilitating safe glutamate uptake.

Ranked Importance of Visual Function Outcome Measures in Choroideremia Clinical Trials.

Purpose: Clinical trials of novel therapies for choroideremia require robust and clinically meaningful visual function outcome measures. Best-corrected visual acuity (BCVA) is mostly insensitive to changes in disease state, until late stages, and hence also to potential therapeutic gains after gene therapies. While the insensitivity of BCVA as an effective outcome measure is common wisdom, its low importance has not been rigorously demonstrated in the literature.

Retinal Patterns and the Role of Autofluorescence in Choroideremia.

Background: Choroideremia is a monogenic inherited retinal dystrophy that manifests in males with night blindness, progressive loss of peripheral vision, and ultimately profound sight loss, commonly by middle age. It is caused by genetic defects of the gene, which result in a deficiency in Rab-escort protein-1, a key element for intracellular trafficking of vesicles, including those carrying melanin. As choroideremia primarily affects the retinal pigment epithelium, fundus autofluorescence, which focuses on the fluorescent properties of pigments within the retina, is an established imaging modality used for the assessment and monitoring of affected patients.

XOLARIS: A 24-Month, Prospective, Natural History Study of 201 Participants with -Associated X-Linked Retinitis Pigmentosa.

Objective: To improve the understanding of the natural disease progression of ()associated X-linked retinitis pigmentosa (XLRP).

Design: A multicenter, prospective, observational natural history study over 24 months.

Participants: Male participants aged ≥7 years with a pathogenic variant in the gene, a best-corrected visual acuity (BCVA) score of ≥34 ETDRS letters, and a mean 68-loci retinal sensitivity (assessed by microperimetry) of 0.

Real-world six-month outcomes in patients switched to faricimab following partial response to anti-VEGF therapy for neovascular age-related macular degeneration and diabetic macular oedema.

Background: Landmark studies reported on faricimab efficacy and safety predominantly in treatment naïve patients, but outcomes following switch from other anti-VEGF therapies are lacking. We evaluated patients switched to faricimab who had previously shown a partial response to other anti-VEGF injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO).

Methods: Retrospective study at the Oxford Eye Hospital.

Exploring Scotopic Microperimetry as an Outcome Measure in Choroideremia.

Purpose: Choroideremia is an X-linked outer retinal degeneration. Early symptoms include nyctalopia and progressive visual field loss, but visual acuity is preserved until late disease stages. Dark-adapted two-color fundus-controlled perimetry (also known as scotopic microperimetry) has been developed to enable spatial assessment of rod and cone photoreceptor function.

A novel frameshift variant in gene mimicking choroideremia carrier retinopathy.

Background: Danon disease is a rare, multisystemic X-linked dominant disorder caused by variants in the gene. It can be associated with retinal degeneration, but this is not well characterized. Here we describe a late presentation of a mild retinal phenotype, initially diagnosed as choroideremia carrier, associated with a novel variant in the gene.

Establishing Clinical Trial Endpoints in Selecting Patients for RPGR Retinal Gene Therapy.

Purpose: Clinical trials for X-linked retinitis pigmentosa (RP) often assess retinal structure using optical coherence tomography (OCT) and function using microperimetry to evaluate initial eligibility and endpoints. Therefore, we seek to determine which parameters might be most sensitive in screening new patients for enrollment.

Methods: Thirty-one patients (62 eyes) with confirmed retinitis pigmentosa GTPase regulator (RPGR) mutations attending Oxford Eye Hospital were included in this retrospective analysis.

Expanding the genotypic and phenotypic spectra with a novel variant in the ciliopathy gene, , associated with selective cone degeneration.

Background: (Cilia and Flagella Associated Protein 410) encodes a protein that has an important role in the development and function of cilia. In ophthalmology, pathogenic variants in have been described in association with cone rod dystrophy, retinitis pigmentosa, with or without macular staphyloma, or with systemic abnormalities such as skeletal dysplasia and amyotrophic lateral sclerosis. Herein, we report a consanguineous family with a novel homozygous c.

Single-cell transcriptomic analysis of retinal immune regulation and blood-retinal barrier function during experimental autoimmune uveitis.

Uveitis is characterised by breakdown of the blood-retinal barrier (BRB), allowing infiltration of immune cells that mediate intraocular inflammation, which can lead to irreversible damage of the neuroretina and the loss of sight. Treatment of uveitis relies heavily on corticosteroids and systemic immunosuppression due to limited understanding of disease pathogenesis. We performed single-cell RNA-sequencing of retinas, as well as bulk RNA-sequencing of retinal pigment epithelial (RPE) cells from mice with experimental autoimmune uveitis (EAU) versus healthy control.

Retinal Focal Nodular Gliosis (Vasoproliferative Tumors) Have Varied Clinical Courses Requiring Tailored Management: A Case Series.

Introduction: Retinal focal nodular gliosis (FNG), also known as vasoproliferative tumors (VPTs), are rare, benign vascular tumors associated with exudation with no current consensus on management. Herein, we describe the varied clinical course and management of 3 patients with retinal FNG, one of whom is associated with retinitis pigmentosa.

Case Presentations: Case 1 is a 76-year-old female who presented with reduced vision and distortion secondary to a vitreous hemorrhage and epiretinal membrane (ERM) as complications of a known small peripheral retinal FNG.

Correlation Between Serum and CSF Concentrations of Midazolam and 1-Hydroxy-Midazolam in Critically Ill Neurosurgical Patients.

Background: Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized.

Objective: This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation.

Longitudinal assessment of female carriers of choroideremia using multimodal retinal imaging.

Background/aims: Female choroideremia carriers present with a spectrum of disease severity. Unlike in men, the rate of disease progression has not been well characterised in carriers. This longitudinal study aimed to determine the rate of retinal degeneration in choroideremia carriers, using multimodal imaging and microperimetry.

Investigating the impact of asymmetric macular sensitivity on visual acuity chart reading in choroideremia.

Introduction: Degeneration in choroideremia, unlike typical centripetal photoreceptor degenerations, is centred temporal to the fovea. Once the fovea is affected, the nasal visual field (temporal retina) is relatively spared, and the preferred retinal locus shifts temporally. Therefore, when reading left to right, only the right eye reads into a scotoma.

An Open-Label Phase II Study Assessing the Safety of Bilateral, Sequential Administration of Retinal Gene Therapy in Participants with Choroideremia: The GEMINI Study.

Choroideremia, an incurable, progressive retinal degeneration primarily affecting young men, leads to sight loss. GEMINI was a multicenter, open-label, prospective, two-period, interventional Phase II study assessing the safety of bilateral sequential administration of timrepigene emparvovec, a gene therapy, in adult males with genetically confirmed choroideremia (NCT03507686, ClinicalTrials.gov).

Robotising vitreoretinal surgeries.

The use of robotic surgery in ophthalmology has been shown to offer many potential advantages to current surgical techniques. Vitreoretinal surgery requires complex manoeuvres and high precision, and this is an area that exceeds manual human dexterity in certain surgical situations. With the advent of advanced therapeutics such as subretinal gene therapy, precise delivery and minimising trauma is imperative to optimize outcomes.

Retinal Characteristics of Female Choroideremia Carriers: Multimodal Imaging, Microperimetry, and Genetics.

Purpose: To describe visual function and retinal features of female carriers of choroideremia (CHM), using multimodal imaging and microperimetry.

Design: Cross-sectional cohort study.

Participants And Controls: Choroideremia carriers seen in Australia (Melbourne or Perth) or the United Kingdom (Oxford or Cambridge) between 2012 and 2023.

Robot-Assisted Eye Surgery: A Systematic Review of Effectiveness, Safety, and Practicality in Clinical Settings.

Purpose: Surgical innovation in ophthalmology is impeded by the physiological limits of human motion, and robotic assistance may facilitate an expansion of the surgical repertoire. We conducted a systematic review to identify ophthalmic procedures in which robotic systems have been trialled, evaluate their performance, and explore future directions for research and development of robotic techniques.

Methods: The Cochrane Library, Embase, MEDLINE, Scopus, and Web of Science were searched.