A thematic analysis of patients' experiences of receiving treatment for Neovascular age-related macular degeneration (nAMD).

Background/objectives: A positive patient experience is a key element of quality healthcare but data on the patient experience is rarely collected as part of routine care. This study analysed survey and discussion group comments from patients treated for neovascular AMD (nAMD) treatment to identify key elements of the patient experience.

Subjects/methods: Free text comments from an online Macular Society member survey and quotes from subsequent, local, in-person patient discussion groups were reviewed.

Expansion of the ABCA4-Associated Retinopathy Spectrum: Severe Variants Can be Associated With Early-Onset Severe Retinal Dystrophy.

Purpose: Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are inherited retinal diseases that are characterized by severe visual loss very early in life. Whereas LCA is characterized by loss of vision in the first year of life, nystagmus, and absent or abnormal electrical signals on electroretinogram, persons with EOSRD show onset of disease between 1 and 5 years of age, with better preserved visual acuity and some signals on an electroretinogram. We investigated the genetic cause of disease and clinical characteristics in three probands with EOSRD.

Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6.

Purpose: To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect.

Methods: Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations.

Factors associated with achieving various visual acuity outcomes during loading doses of aflibercept 2 mg for treatment naïve exudative age-related macular degeneration: PRECISE Study Report 7.

Purpose: To identify demographic and baseline OCT characteristics that are predictive of VA outcomes after the first and post-loading injections in patients treated with 2 mg aflibercept.

Methods: This study evaluated VA outcomes in 1999 eyes of 1862 patients with nAMD initiated on aflibercept therapy. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA outcome defined as VA ≥ 68 ETDRS letters (Snellen ≥  6/12) and poor VA outcome of <54 ETDRS letters (Snellen < 6/18) or a loss of ≥5 ETDRS letters after first and post-loading injections were analysed using logistic regression via generalised estimating equations.

Elevated Plasma Complement Factors in CRB1-Associated Inherited Retinal Dystrophies.

Purpose: To determine the profile of inflammation-related proteins and complement system factors in the plasma of CRB1-associated inherited retinal dystrophies (CRB1-IRDs).

Methods: We used the Olink Explore 384 Inflammation II panel for targeted proteomics in 30 cases and 29 controls (cohort I) to identify immune pathways involved in CRB1-IRDs. Genotyping was performed in cohort I and a second cohort of 123 patients from 14 countries and 1292 controls (cohort II).

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Glycogen myophosphorylase loss causes increased dependence on glucose in iPSC-derived retinal pigment epithelium.

Loss of glycogen myophosphorylase (PYGM) expression results in an inability to break down muscle glycogen, leading to McArdle disease-an autosomal recessive metabolic disorder characterized by exercise intolerance and muscle cramps. While previously considered relatively benign, this condition has recently been associated with pattern dystrophy in the retina, accompanied by variable sight impairment, secondary to retinal pigment epithelial (RPE) cell involvement. However, the pathomechanism of this condition remains unclear.

Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5.

Objective: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD).

Methods: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response.

Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4.

Purpose: To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept.

Methods: Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness.

Associations of presenting visual acuity with morphological changes on OCT in neovascular age-related macular degeneration: PRECISE Study Report 2.

Purpose: To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD).

Methods: Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA ≥ 68 ETDRS letters, Snellen ≥ 6/12) and poor VA (VA < 54 letters, Snellen < 6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation.

Long-Read Nanopore Sequencing of RPGR ORF15 is Enhanced Following DNase I Treatment of MinION Flow Cells.

Introduction: RPGR ORF15 is an exon present almost exclusively in the retinal transcript of RPGR. It is purine-rich, repetitive and notoriously hard to sequence, but is a hotspot for mutations causing X-linked retinitis pigmentosa.

Methods: Long-read nanopore sequencing on MinION and Flongle flow cells was used to sequence RPGR ORF15 in genomic DNA from patients with inherited retinal dystrophy.

A Multi-Modal AI-Driven Cohort Selection Tool to Predict Suboptimal Non-Responders to Aflibercept Loading-Phase for Neovascular Age-Related Macular Degeneration: PRECISE Study Report 1.

Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies.

Haplotyping Using Long-Range PCR and Nanopore Sequencing to Phase Variants: Lessons Learned From the ABCA4 Locus.

Short-read next-generation sequencing has revolutionized our ability to identify variants underlying inherited diseases; however, it does not allow the phasing of variants to clarify their diagnostic interpretation. The advent of widespread, increasingly accurate long-read sequencing has opened up new applications not currently available through short-read next-generation sequencing. One such use is the ability to phase variants to clarify their diagnostic interpretation and to investigate the increasingly prevalent role of cis-acting variants in the pathogenesis of the inherited disease, so-called complex alleles.

Targeted nanopore sequencing enables complete characterisation of structural deletions initially identified using exon-based short-read sequencing strategies.

Background: The widespread adoption of exome sequencing has greatly increased the rate of genetic diagnosis for inherited conditions. However, the detection and validation of large deletions remains challenging. While numerous bioinformatics approaches have been developed to detect deletions from whole - exome sequencing and targeted panels, further work is typically required to define the physical breakpoints or integration sites.

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis.

Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability.

Associations with Non-Persistence with Intra-Vitreal Therapy for Neovascular Age-Related Macular Degeneration at 24 Months.

Aims: The aim of the study was to investigate non-persistence with treatment for neovascular age-related macular degeneration (NvAMD) before day 720 (24 months) after initiation, explore associations with baseline characteristics and variation between sites.

Methods: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts for NvAMD eyes starting intra-vitreal therapy from 2017 to 2018. Time to non-persistence with treatment, defined as no recorded attendance for either monitoring or treatment for a period ≥6 months, was visualised with a Kaplan-Meier survival plot.

UNITED KINGDOM DATABASE STUDY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX) FOR MACULAR EDEMA RELATED TO RETINAL VEIN OCCLUSION.

Purpose: To study the treatment patterns, visual outcomes and safety profile of intravitreal dexamethasone implant (IDI) used for the treatment of macular edema secondary to retinal vein occlusion.

Methods: Up to 2 years of routinely collected anonymized data within electronic medical record systems were remotely extracted from 16 centers. The outcome measures include visual outcome, number of injections, and safety measures, including the rate of intraocular pressure (IOP) rise, frequency of IOP-lowering medication usage, and cataract surgery rates.

Outcome of Cataract Surgery in Patients With Retinitis Pigmentosa.

Purpose: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP).

Design: Retrospective, noncomparative clinical study.

Methods: Preoperative, intraoperative, and postoperative data of patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe.

Associations with visual acuity outcomes after 12 months of treatment in 9401 eyes with neovascular AMD.

Objective: To record visual acuity outcomes after 12 months of treatment for neovascular age-related macular degeneration (NvAMD), investigate variation between sites and explore associations with baseline characteristics and care processes.

Methods And Analysis: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Associations with acuity outcomes were investigated using multivariate linear and logistic regression.