Syndromic Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20-30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives.

Dealing with the Verteporfin Shortage: Treatment Options and Outcomes in Patients with Chronic and Non-Resolving Central Serous Chorioretinopathy.

Introduction: Half-dose photodynamic therapy (HD-PDT) with verteporfin is the mainstay treatment in central serous chorioretinopathy (CSC). Since 2021, there is a worldwide shortage of verteporfin. This called for adjustments of daily practice.

Generalizable Deep Learning for the Detection of Incomplete and Complete Retinal Pigment Epithelium and Outer Retinal Atrophy: A MACUSTAR Report.

Purpose: The purpose of this study was to develop a deep learning algorithm for detecting and quantifying incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) in optical coherence tomography (OCT) that generalizes well to data from different devices and to validate in an intermediate age-related macular degeneration (iAMD) cohort.

Methods: The algorithm comprised a domain adaptation (DA) model, promoting generalization across devices, and a segmentation model for detecting granular biomarkers defining iRORA/cRORA, which are combined into iRORA/cRORA segmentations. Manual annotations of iRORA/cRORA in OCTs from different devices in the MACUSTAR study (168 patients with iAMD) were compared to the algorithm's output.

Frequency and Genetic Spectrum of Inherited Retinal Dystrophies in a Large Dutch Pediatric Cohort: The RD5000 Consortium.

Purpose: Gene-based therapies for inherited retinal dystrophies (IRDs) are upcoming. Treatment before substantial vision loss will optimize outcomes. It is crucial to identify common phenotypes and causative genes in children.

Cost-effectiveness of hydroxychloroquine retinopathy screening: the current guideline versus no screening and reduced regimens.

Objective: Hydroxychloroquine (HCQ) effectively treats autoimmune diseases but prolonged use may lead to retinopathy and subsequent vision loss. Guidelines suggest annual follow-up after 5 years for low-risk and 1 year for high-risk patients. This study evaluates the cost-effectiveness of current screening guidelines and a reduced regimen in the Netherlands from a societal perspective.

Uncertainty-aware multiple-instance learning for reliable classification: Application to optical coherence tomography.

Deep learning classification models for medical image analysis often perform well on data from scanners that were used to acquire the training data. However, when these models are applied to data from different vendors, their performance tends to drop substantially. Artifacts that only occur within scans from specific scanners are major causes of this poor generalizability.

Unveiling Statins and Genetics in Age-Related Macular Degeneration: The Coimbra Eye Study-Report 9.

Purpose: To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between statins and genetics.

Methods: In this analysis, 682 subjects made two visits (6.5-year follow-up) of the Coimbra Eye Study.

Twelve-month Natural History Study of Centrosomal Protein 290 (CEP290)-associated Inherited Retinal Degeneration.

Purpose: To define the clinical characteristics of centrosomal protein 290 ()-associated inherited retinal degeneration (IRD) and determine which assessments may provide reliable endpoints in future interventional trials.

Design: Participants in this natural history study were enrolled into 2 best-corrected visual acuity (BCVA) cohorts: light perception to > 1.0 logarithm of the minimum angle of resolution (logMAR) and 1.

Preclinical Development of Antisense Oligonucleotides to Rescue Aberrant Splicing Caused by an Ultrarare Variant in a Child with Early-Onset Stargardt Disease.

Precision medicine is rapidly gaining recognition in the field of (ultra)rare conditions, where only a few individuals in the world are affected. Clinical trial design for a small number of patients is extremely challenging, and for this reason, the development of N-of-1 strategies is explored to accelerate customized therapy design for rare cases. A strong candidate for this approach is Stargardt disease (STGD1), an autosomal recessive macular degeneration characterized by high genetic and phenotypic heterogeneity.

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.

Gait Adaptability and the Effect of Ocular Disorders on Visually Guided Walking in Parkinson's Disease.

Gait disorders are a disabling feature of Parkinson's disease (PD). To avoid falls, people with PD should be able to adequately adapt their gait. This requires correct response inhibition and integration of visual information.

Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm.

Functional Vision in Patients With Biallelic USH2A Variants.

Purpose: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (V) at baseline in patients with biallelic USH2A variants.

Design: Multicenter, international, cross-sectional study.

Methods: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations.

Efficacy of Carbonic Anhydrase Inhibitors on Cystoid Fluid Collections and Visual Acuity in Patients with X-Linked Retinoschisis.

Purpose: To date, there is no standard treatment regimen for carbonic anhydrase inhibitors (CAIs) in X-linked retinoschisis (XLRS) patients. This retrospective study aims to evaluate the efficacy of CAIs on visual acuity and cystoid fluid collections (CFC) in XRLS patients in Dutch and Belgian tertiary referral centers.

Design: Retrospective cohort study.

Structure-function correlation of retinal photoreceptors in PRPH2-associated central areolar choroidal dystrophy patients assessed by high-resolution scanning laser imaging and microperimetry.

Purpose: High Magnification Module (HMM™, Heidelberg Engineering, Heidelberg, Germany) imaging is a novel technique, designed to visualize the retina at a cellular level. To assess the potential of HMM™-based metrics as endpoints for future trials, we evaluated correlations between structural HMM™ cone metrics, spectral-domain OCT (SD-OCT, Heidelberg Engineering, Heidelberg, Germany) and retinal sensitivity on microperimetry (MP, MAIA, CenterVue, Padova, Italy) in healthy subjects and p.(Arg142Trp) PRPH2-associated Central Areolar Choroidal Dystrophy (CACD) patients.

Generation of an iPSC line (RMCGENi020-A) from a patient with Stargardt disease harboring the recurrent intronic ABCA4 variant c.4253+43G>A.

Pathogenic variants in ABCA4 are associated with Stargardt disease (STGD1), an autosomal recessive macular dystrophy characterized by bilateral central vision loss due to a progressive degeneration of retinal cells. An induced pluripotent stem cell (iPSC) line was generated from late-onset STGD1 patient-derived fibroblasts harboring bi-allelic ABCA4 variants by lentivirus-induced reprogramming. The obtained iPSC line (RMCGENi020-A) showed pluripotent features after the reprogramming process.

Quality of life in patients with CRB1-associated retinal dystrophies: A longitudinal study.

Purpose: To assess the longitudinal vision-related quality of life among patients with CRB1-associated inherited retinal dystrophies.

Methods: In this longitudinal questionnaire study, the National Eye Institute Visual Function Questionnaire (39 items, NEI VFQ-39) was applied at baseline, two-year follow-up, and 4-year follow-up in patients with pathogenic CRB1 variants. [Correction added on 20 November 2023, after first online publication: The preceding sentence has been updated in this version.

Targeted sequencing and in vitro splice assays shed light on ABCA4-associated retinopathies missing heritability.

The ABCA4 gene is the most frequently mutated Mendelian retinopathy-associated gene. Biallelic variants lead to a variety of phenotypes, however, for thousands of cases the underlying variants remain unknown. Here, we aim to shed further light on the missing heritability of ABCA4-associated retinopathy by analyzing a large cohort of macular dystrophy probands.

The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients.

This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF ).

Interaction between genetics and the adherence to the Mediterranean diet: the risk for age-related macular degeneration. Coimbra Eye Study Report 8.

Background: Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the macula. Different factors, environmental, genetic and lifestyle, contribute to its onset and progression. However, how they interconnect to promote the disease, or its progression, is still unclear.