Anti-VEGF therapy for proliferative diabetic retinopathy in Kearns-Sayre syndrome.

Purpose: Multiple mitochondrial syndromes, such as Kearns-Sayre, involve the concurrence of diabetes mellitus and inherited pigmentary retinopathy. It is rare, however, for proliferative disease to develop in these patients as existing inner retinal dysfunction is thought to be protective.

Methods: To our knowledge this is the first description of proliferative diabetic retinopathy (PDR) in Kearns-Sayre syndrome.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT.

A multinational survey of potential participant perspectives on ocular gene therapy.

Amidst rapid advancements in ocular gene therapy, understanding patient perspectives is crucial for shaping future treatment choices and research directions. This international cross-sectional survey evaluated knowledge, attitudes, and perceptions of ocular genetic therapies among potential recipients with inherited retinal diseases (IRDs). Survey instruments included the Attitudes to Gene Therapy-Eye (AGT-Eye), EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and Patient Attitudes to Clinical Trials (PACT-22) instruments.

Managing the apparently blind child presenting in the first year of life: A review.

Severe vision impairment and blindness in childhood have a significant health burden on the child, family and society. This review article seeks to provide a structured framework for managing the apparently blind child presenting in the first year of life, starting from a comprehensive history and examination. Different investigation modalities and the increasingly important role of genetics will also be described, in addition to common causes of severe vision impairment.

EQ-5D-5L health utility scores in Australian adults with inherited retinal diseases: A cross-sectional survey.

Purpose: Economic evaluations of interventions for ocular disease require utility scores that accurately represent quality of life in the target population. This study aimed to describe the distribution of EQ-5D-5L utility values among Australian adults with symptomatic inherited retinal diseases (IRDs) and to assess the relationship between these scores and vision-related quality of life.

Methods: A survey was administered predominantly online in 2021.

Suspected case of benign familial fleck retina with functional loss.

Key Clinical Message: Inherited retinal dystrophies typically affect vision in early childhood; however, this case highlights a late onset retinal dystrophy presenting in midlife and the need for extended visual electrophysiology testing to determine the etiology.

Abstract: A 53-year-old female was referred for visual electrophysiology following a routine optometric eye examination in which yellow flecks were noted in both fundi and the patient had reported a recent near accident whilst driving at night. There was no reported family history of eye disease.

A natural history study of autosomal dominant GUCY2D-associated cone-rod dystrophy.

Purpose: To describe the natural history of autosomal dominant (AD) GUCY2D-associated cone-rod dystrophies (CRDs), and evaluate associated structural and functional biomarkers.

Methods: Retrospective analysis was conducted on 16 patients with AD GUCY2D-CRDs across two sites. Assessments included central macular thickness (CMT) and length of disruption to the ellipsoid zone (EZ) via optical coherence tomography (OCT), electroretinography (ERG) parameters, best corrected visual acuity (BCVA), and fundus autofluorescence (FAF).

Prevalence of Glaucoma Following Paediatric Cataract Surgery in an Australian Tertiary Referral Centre.

Purpose: Secondary glaucoma following childhood cataract surgery remains the most common complication in the paediatric population. This study aimed to determine the incidence, time to progression and risk factors associated with the development of secondary glaucoma following childhood cataract surgery in a paediatric population. Outcome measures were the detection of secondary glaucoma, postoperative time frame to development of glaucoma and risk factors in its development.

The health care and societal costs of inherited retinal diseases in Australia: a microsimulation modelling study.

Objectives: To estimate the health care and societal costs of inherited retinal diseases (IRDs) in Australia.

Design, Setting, Participants: Microsimulation modelling study based on primary data - collected in interviews of people with IRDs who had ophthalmic or genetic consultations at the Children's Hospital at Westmead or the Save Sight Institute (both Sydney) during 1 January 2019 - 31 December 2020, and of their carers and spouses - and linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Schedule (PBS) data.

Main Outcome Measures: Annual and lifetime costs for people with IRDs and for their carers and spouses, grouped by payer (Australian government, state governments, individuals, private health insurance) and type (health care costs; societal costs: social support, National Disability Insurance Scheme (NDIS), income and taxation, costs associated with caring for family members with IRDs); estimated annual national cost of IRDs.

-associated autosomal dominant retinitis pigmentosa: natural history of novel variant Lys314Gln and a comprehensive literature search.

Background: Inosine monophosphate dehydrogenase (IMPDH) is a key regulatory enzyme in the de novo synthesis of the purine base guanine. Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) are causative for RP10 autosomal dominant retinitis pigmentosa (adRP). This study reports a novel variant in a family with IMPDH1-associated retinopathy.

Spectrum of ocular disease in children aged between 0 and 3 years at an Australian paediatric tertiary hospital.

Background: Childhood ocular disease can be a significant health burden to the child, family and society. Previous studies have examined the spectrum of paediatric ocular disease presenting to tertiary hospitals; however, these studies have broader age ranges, smaller sample sizes, and are largely based in developing countries. This study aims to assess the spectrum of ocular disease in the first 3 years of life presenting to the eye department of an Australian tertiary paediatric hospital.

Early recognition of CLN3 disease facilitated by visual electrophysiology and multimodal imaging.

Background: Neuronal ceroid lipofuscinosis is a group of neurodegenerative disorders with varying visual dysfunction. CLN3 is a subtype which commonly presents with visual decline. Visual symptomatology can be indistinct making early diagnosis difficult.

Survey of perspectives of people with inherited retinal diseases on ocular gene therapy in Australia.

Many gene therapies are in development for treating people with inherited retinal diseases (IRD). We hypothesized that potential recipients of gene therapy would have knowledge gaps regarding treatment. We aimed to assess knowledge, attitudes, and perceptions of genetic therapies among potential recipients with IRD, using a novel instrument we designed (Attitudes to Gene Therapy-Eye (AGT-Eye)) and their associations with demographic data, self-reported visual status, and tools assessing quality of life and attitudes toward clinical trials using a community-based cross-sectional survey of Australian adults with IRD.

Eye Abnormalities in Children with Fetal Alcohol Spectrum Disorders: A Systematic Review.

Purpose: Although eye abnormalities are reported in fetal alcohol spectrum disorders (FASD), no systematic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines has been undertaken. Our aim was to document the range and prevalence of eye abnormalities reported in children with prenatal alcohol exposure (PAE) and/or FASD.

Methods: Searches of electronic databases and manual searches.

Electrophysiological Assessment in Birdshot Chorioretinopathy: Flicker Electroretinograms Recorded With a Handheld Device.

Purpose: The flicker electroretinogram (ERG) is a sensitive indicator of retinal dysfunction in birdshot chorioretinopathy (BCR). We explored recordings from a handheld device in BCR, comparing these with conventional recordings in the same patients and with handheld ERGs from healthy individuals.

Methods: Non-mydriatic flicker ERGs, using the handheld RETeval system (LKC Technologies), were recorded with skin electrodes at two centers.

Whole Genome Sequencing, Focused Assays and Functional Studies Increasing Understanding in Cryptic Inherited Retinal Dystrophies.

The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy.

Human iPSC-Derived Retinal Organoids and Retinal Pigment Epithelium for Novel Intronic Variant Assessment for Therapy Suitability.

The RPGR gene encodes Retinitis Pigmentosa GTPase Regulator, a known interactor with ciliary proteins, which is involved in maintaining healthy photoreceptor cells. Variants in RPGR are the main contributor to X-linked rod-cone dystrophy (RCD), and RPGR gene therapy approaches are in clinical trials. Hence, elucidation of the pathogenicity of novel RPGR variants is important for a patient therapy opportunity.

Electronegative electroretinogram in the modern multimodal imaging era.

Background: The electronegative electroretinogram (ERG) reflecting inner retinal dysfunction can assist as a diagnostic tool to determine the anatomical location in eye disease. The aim of this study is to determine the frequency and aetiology of electronegative ERG in a tertiary ophthalmology centre and to develop a clinical algorithm to assist patient management.

Methods: Retrospective review of ERGs performed at the Save Sight Institute from January 2011 to December 2020.

Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials.

The study of individual differences in perception at absolute threshold has a rich history, with much of the seminal work being driven by the need to identify those with superior abilities in times of war. Although the popularity of such testing waned in the latter half of the 20th century, interest in measures of visual function at the absolute limit of vision is increasing, partly in response to emerging treatments for retinal diseases, such as gene therapy and cellular therapies, that demand "new" functional measures to assess treatment outcomes. Conventional clinical, or clinical research, testing approaches generally assess rod sensitivity at or near absolute threshold; however, cone sensitivity is typically assayed in the presence of adapting backgrounds.

Approach to childhood glaucoma: A review.

Childhood glaucoma represents a heterogenous group of rare ocular conditions that may result in significant sight threatening complications related to elevated intraocular pressure (IOP). It can be classified as either primary or secondary and the latter may have systemic associations. This review will be based on the work of the childhood glaucoma research network (CGRN) and will focus on the diagnosis and management of the most common types of childhood glaucoma.

Evaluation for Retinal Therapy for Variation Assessed in hiPSC Retinal Pigment Epithelial Cells.

Human induced pluripotent stem cells (hiPSCs) generated from patients and the derivative retinal cells enable the investigation of pathological and novel variants in relevant cell populations. Biallelic pathogenic variants in cause early-onset severe retinal dystrophy (EOSRD) or Leber congenital amaurosis (LCA). Increasingly, regulatory-approved retinal gene replacement therapy is available for patients with these clinical features, but only if they have biallelic pathological variants and sufficient viable retinal cells.

Cataract Surgery in Short Eyes, Including Nanophthalmos: Visual Outcomes, Complications and Refractive Results.

Background: To report the visual outcomes, complications and refractive results of phacoemulsification surgery and intraocular lens implantation in a large series of adult patients with short and nanophthalmic eyes.

Methods: The records of all patients with axial length <21.0 mm undergoing phacoemulsification with intraocular lens implantation at an adult teaching hospital were retrospectively reviewed.