When do patients with retinitis pigmentosa present to ophthalmologists? A multi-centre retrospective study.

Background: Planned gene therapies for retinitis pigmentosa (RP) depend on viable photoreceptors for efficacy. Understanding disease severity at presentation, and drivers that influence time to presentation is important when planning interventions. We examined features that influence RP severity at initial presentation.

A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease.

Purpose: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution.

Design: Retrospective, single-institution cohort review.

Participants: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4.

Diagnostic Challenges in -Associated Retinal Degeneration: One Gene, Many Phenotypes.

(1) Purpose: -associated retinal degeneration (-RD) is a phenotypically diverse disease that often evades diagnosis, even by experienced retinal specialists. This may lead to inappropriate management, delayed genetic testing, or inaccurate interpretation of genetic testing results. Here, we illustrate the phenotypic diversity of -RD using a series of representative cases and compare these to other conditions that closely mimic -RD.

Using Goldmann Visual Field Volume to Track Disease Progression in Choroideremia.

Purpose: Choroideremia is an X-linked choroidopathy caused by pathogenic variants in the gene. It is characterized by the early appearance of multiple scotomas in the peripheral visual field that spread and coalesce, usually sparing central vision until late in the disease. These features make quantitative monitoring of visual decline particularly challenging.

Demonstration of the pathogenicity of a common non-exomic mutation in ABCA4 using iPSC-derived retinal organoids and retrospective clinical data.

Mutations in ABCA4 are the most common cause of Mendelian retinal disease. Clinical evaluation of this gene is challenging because of its extreme allelic diversity, the large fraction of non-exomic mutations, and the wide range of associated disease. We used patient-derived retinal organoids as well as DNA samples and clinical data from a large cohort of patients with ABCA4-associated retinal disease to investigate the pathogenicity of a variant in ABCA4 (IVS30 + 1321 A>G) that occurs heterozygously in 2% of Europeans.

Surgical Technique to Treat Presbyopic Inlay-Associated Corneal Haze With Sequential Excimer Photoablation: A Case Series.

Purpose: To describe an approach using sequential excimer laser ablation of the stromal surface of the corneal flap with or without subsequent excimer ablation to the stromal bed to reduce presbyopic inlay-associated corneal haze.

Methods: Twelve patients who underwent KAMRA inlay (Acufocus) explantation due to corneal haze were included. The mean interval between explantation and the primary surgery (phototherapeutic keratotomy [PTK] to corneal flap) was 16.

RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations.

Purpose: The study aimed to describe the phenotypic features of retinitis pigmentosa (RP) associated with the previously described EYS C2139Y variant in Singaporeans and establish the importance of this variant as a prevalent cause of RP among East Asians.

Methods: A clinical phenotyping and exome-sequencing study was conducted on consecutive patients with nonsyndromic RP. Epidemiological analysis was performed using Singaporean and global population-based genetic data.

Long-term functional and structural outcomes in X-linked retinoschisis: implications for clinical trials.

Introduction: X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, . Affected individuals develop retinal layer separation, leading to loss of visual acuity (VA). Several XLRS gene therapy trials have been attempted but none have met their primary endpoints.

The economic burden of inherited retinal disease in Singapore: a prevalence-based cost-of-illness study.

Objective: To assess the economic impact of inherited retinal disease (IRD) among Singaporeans.

Methods: IRD prevalence was calculated using population-based data. Focused surveys were conducted for sequentially enrolled IRD patients from a tertiary hospital.

Characterizing the genotypic spectrum of retinitis pigmentosa in East Asian populations: a systematic review.

Background: Ongoing trials for retinitis pigmentosa (RP) are genotype-specific, with most trials conducted on European cohorts. Due to genetic differences across diverse ancestries and populations, these therapies may not be efficacious in East Asians.

Materials And Methods: A literature search was conducted from 1966 to September 2022 for cohort studies on East Asian populations reporting on non-syndromic RP genotypes and variants.

Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.

Purpose: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort.

Methods: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort.

PATTERN AND CHARACTERISTICS OF DRUSEN SUBTYPES IN CHINESE AND INDIAN POPULATIONS IN SINGAPORE.

Purpose: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness.

Methods: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited.

Associations between age-related macular degeneration and sleep dysfunction: A systematic review.

Background: Age-related macular degeneration, a prevalent degenerative retinal disease, is associated with non-visual and psychosocial impairments that may affect sleep. In this systematic review, we evaluated associations between age-related macular degeneration (AMD) and sleep, highlighted knowledge gaps and provided evidence-based recommendations to clinicians to enable holistic management of AMD patients.

Methods: We searched PubMed, Embase and the Cochrane Central registries for papers published before May 2022.

Novel volumetric imaging biomarkers for assessing disease activity in eyes with PCV.

The aim of this study was to evaluate influence of baseline imaging features on visual and anatomical outcomes in eyes with PCV treated with anti-VEGF monotherapy. In this prospective study we enrolled participants with treatment-naïve PCV who followed a treat-and-extend protocol using intravitreal aflibercept (IVA) monotherapy. Baseline clinical features evaluatedincluded best corrected visual acuity (BCVA), traditional features such as lesion size, fluid-related OCT parameters and novel parameters using automated software.

Gene-Based Therapeutics for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber's congenital amaurosis due to mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations.

Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress.

Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs.

Real-world cost-effectiveness of anti-VEGF monotherapy and combination therapy for the treatment of polypoidal choroidal vasculopathy.

Objectives: For patients with polypoidal choroidal vasculopathy (PCV), intravitreal anti-vascular endothelial growth factor (anti-VEGF) combination therapy has been shown to be cost-saving relative to monotherapy in a clinical trial setting. However, whether this also applies to real-world settings is unclear. We aim to compare the real-world functional outcomes and cost-effectiveness of intravitreal anti-VEGF combination therapy relative to monotherapy, to investigate whether combination therapy is truly cost-saving.

Six-year incidence of age-related macular degeneration and correlation to OCT-derived drusen volume measurements in a Chinese population.

Aims: To report the 6-year incidence of optical coherence tomography (OCT)-derived age-related changes in drusen volume and related systemic and ocular associations.

Methods: Chinese adults aged 40 years and older were assessed at baseline and 6 years with colour fundus photography (CFP) and spectral domain (SD) OCT. CFPs were graded for age-related macular degeneration (AMD) features and drusen volume was generated using commercially available automated software.

Clinical operational considerations and responses to lockdown and reopening in the Covid-19 pandemic: experience of a tertiary ophthalmology centre in Singapore.

Background: Much has been written on infection control and clinical measures for ophthalmic institutions and departments to cope with the COVID-19 pandemic. However, few articles have detailed implementation plans to manage lockdowns and subsequent re-openings. In this article, specific operational responses and their outcomes in a large tertiary ophthalmology centre are described.

Evolving treatment paradigms for PCV.

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular AMD (nAMD) that accounts for a significant proportion of nAMD cases worldwide, and particularly in Asia. Contemporary PCV treatment strategies have closely followed those used in typical nAMD, though there are significant gaps in knowledge on PCV management and it remains unclear if these strategies are appropriate. Current clinical trial data suggest intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy is effective in managing haemorrhage and exudation in PCV, although the optimal treatment interval, including as-needed and treat-and-extend approaches, is unclear.