Breaking bad news in ophthalmology: a pilot skills workshop for residents.

Objective: To design and implement a formal skills workshop for ophthalmology residents to practice breaking bad news.

Methods: A 2-session workshop was developed for 7 ophthalmology residents at the University of Alberta based on a workshop published by Ohio State University. Residents discussed the SPIKES protocol for breaking bad news, practiced mock cases with standardized patients, and listened to shared experiences from patients who had received ocular diagnoses.

Overcoming the Challenges to Clinical Development of X-Linked Retinitis Pigmentosa Therapies: Proceedings of an Expert Panel.

Unlabelled: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease manifesting as impaired night vision and peripheral vision loss that progresses to legal blindness. Although several trials of ocular gene therapy for XLRP have been conducted or are in progress, there is currently no approved treatment. In July 2022, the Foundation Fighting Blindness convened an expert panel to examine relevant research and make recommendations for overcoming the challenges and capitalizing on the opportunities in conducting clinical trials of RPGR-targeted therapy for XLRP.

Pseudoxanthoma elasticum and retinitis pigmentosa in a patient with a novel mutation in the gene.

Background: Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP).

AAV2-Mediated Gene Therapy for Choroideremia: 5-Year Results and Alternate Anti-sense Oligonucleotide Therapy.

Purpose: To assess the long-term safety and efficacy of AAV2-REP1 in choroideremia (CHM) patients, and to test a potential antisense oligonucleotide therapy for CHM.

Design: Extended, prospective phase 1/2 clinical trial and laboratory investigation.

Methods: Five patients who received a single subfoveal injection of AAV2-REP1 were studied.

Upward saccadic intrusions as the presenting feature for incomplete congenital stationary night blindness.

We describe the case of a 9-month-old boy presenting with isolated intermittent vertical eye movements most in keeping with upward saccadic pulses, a form of saccadic intrusions. Full-field electroretinogram was consistent with a generalized retinal dystrophy, and genetic testing revealed a hemizygous pathogenic mutation in the CACNA1F gene, confirming the diagnosis of incomplete congenital stationary night blindness (iCSNB). This case describes vertical saccadic pulses as the sole presenting sign of a retinal dystrophy.

The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision.

Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes.

Zebrafish and inherited photoreceptor disease: Models and insights.

Photoreceptor dysfunctions and degenerative diseases are significant causes of vision loss in patients, with few effective treatments available. Targeted interventions to prevent or reverse photoreceptor-related vision loss are not possible without a thorough understanding of the underlying mechanism leading to disease, which is exceedingly difficult to accomplish in the human system. Cone diseases are particularly challenging to model, as some popular genetically modifiable model animals are nocturnal with a rod-dominant visual system and cones that have dissimilarities to human cones.

Lessons learned from research on choroideremia.

Having devoted over 35 years of my professional life to various projects on choroideremia (CHM), I began to reflect on the many lessons that I learned along the way. One of the most important is: we should pay careful attention to possible, unintended psychological harm in clinical research. This lesson was learned early and then reinforced when I engaged CHM patients in an investigator-sponsored Phase IB clinical trial of ocular gene therapy for choroideremia.

Validating Ellipsoid Zone Area Measurement With Multimodal Imaging in Choroideremia.

Purpose: To assess en face ellipsoid zone (EZ) maps of remaining retinal structure as outcome measures for the future clinical research in patients with choroideremia.

Methods: Twenty eyes from 12 patients with a confirmed genetic diagnosis of choroideremia were included retrospectively from a single site. From spectral domain-optical coherence tomography volume scans, slabs including the EZ were manually segmented to create the en face EZ maps.

Mutations in Peroxisomal Biogenesis Disorders: An Usher Syndrome Mimic.

Purpose: Peroxisomal biogenesis disorders (PBDs) represent a spectrum of conditions that result in vision loss, sensorineural hearing loss, neurologic dysfunction, and other abnormalities resulting from aberrant peroxisomal function caused by mutations in genes. With no treatments currently available, we sought to investigate the disease mechanism in a patient with a PBD caused by defects in and to probe whether overexpression of could restore peroxisome function and potentially offer therapeutic benefit.

Design: Laboratory-based study.

A homozygous variant causes recessive cone-rod dystrophy.

: To report a case of initial cone dystrophy that advanced to a cone-rod dystrophy with homozygous variants in the gene.: Retinal structure and visual function assessments were performed using fundoscopy, spectral-domain optical coherence tomography, full field electroretinography, semi-kinetic perimetry, and Ishihara plate testing. A DNA sample was collected and sent for diagnostic molecular genetic testing with a cone-rod dystrophy panel.

Zebrafish Models of Photoreceptor Dysfunction and Degeneration.

Zebrafish are an instrumental system for the generation of photoreceptor degeneration models, which can be utilized to determine underlying causes of photoreceptor dysfunction and death, and for the analysis of potential therapeutic compounds, as well as the characterization of regenerative responses. We review the wealth of information from existing zebrafish models of photoreceptor disease, specifically as they relate to currently accepted taxonomic classes of human rod and cone disease. We also highlight that rich, detailed information can be derived from studying photoreceptor development, structure, and function, including behavioural assessments and in vivo imaging of zebrafish.

Progressive Photoreceptor Dysfunction and Age-Related Macular Degeneration-Like Features in Mutant Zebrafish.

Photoreceptor disease results in irreparable vision loss and blindness, which has a dramatic impact on quality of life. Pathogenic mutations in lead to photoreceptor degenerations such as occult macular dystrophy and retinitis pigmentosa. RP1L1 is a component of the photoreceptor axoneme, the backbone structure of the photoreceptor's light-sensing outer segment.

Severe retinal degeneration in a patient with Canavan disease.

Canavan disease is an autosomal recessive, neurodegenerative disorder caused by mutations in , a gene encoding the enzyme aspartoacylase. Patients present with macrocephaly, developmental delay, hypotonia, vision impairment and accumulation of -acetylaspartic acid. Progressive white matter changes occur in the central nervous system.

A diagnostic approach to syndromic retinal dystrophies with intellectual disability.

Inherited retinal dystrophies are a group of monogenic disorders that, as a whole, contribute significantly to the burden of ocular disease in both pediatric and adult patients. In their syndromic forms, retinal dystrophies can be observed in association with intellectual disability, frequently alongside other systemic manifestations. There are now over 80 genes implicated in syndromic retinal dystrophies with intellectual disability.

Improved electroretinographic responses following dietary intervention in a patient with Refsum disease.

Refsum disease is a rare inherited metabolic disorder arising from a defect in peroxisomal metabolism. Patients lack the functional enzyme phytanoyl-CoA hydroxylase, resulting in perturbed alpha oxidation of fatty acids. Phytanic acid accumulates in nervous and adipose tissue and leads to several disease phenotypes including early-onset retinal degeneration, hearing loss, peripheral neuropathy, anosmia, and cerebellar ataxia, among others.

Ocular Gene Therapy with Adeno-associated Virus Vectors: Current Outlook for Patients and Researchers.

In this "Perspective", we discuss ocular gene therapy - the patient's perspective, the various strategies of gene replacement and gene editing, the place of adeno-associated virus vectors, routes of delivery to the eye and the remaining question - "why does immunity continue to limit efficacy?" Through the coordinated efforts of patients, researchers, granting agencies and industry, and after many years of pre-clinical studies, biochemical, cellular, and animal models, we are seeing clinical trials emerge for many previously untreatable heritable ocular disorders. The pathway to therapies has been led by the successful treatment of the RPE65 form of Leber congenital amaurosis with LUXTURNA . In some cases, immune reactions to the vectors continue to occur, limiting efficacy.