A cost-minimization analysis of anti-VEGFs for the treatment of neovascular age-related macular degeneration in the Netherlands.

Objective: Age-related macular degeneration (AMD) is the main cause of severe vision loss globally. Neovascular AMD (nAMD) is an advanced stage of AMD treated with anti-vascular endothelial growth factors (anti-VEGFs). Although anti-VEGF treatment is effective, the frequent intravitreal injections place a burden on patients, (in)formal caregivers, and clinics.

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.

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism.

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

DNA methylation (DNAm) provides a crucial epigenetic mark linking genetic variations to environmental influence. We analyzed array-based DNAm profiles of 160 human retinas with co-measured RNA-seq and > 8 million genetic variants, uncovering sites of genetic regulation in (37,453 mQTLs and 12,505 eQTLs) and 13,747 eQTMs (DNAm loci affecting gene expression), with over one-third specific to the retina. mQTLs and eQTMs show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism.

Adherence to the Mediterranean Diet and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2.

Purpose: To determine whether closer adherence to a Mediterranean diet (and its individual components) was associated with altered risk of progression to late age-related macular degeneration (AMD) and large drusen. Additional objectives were to assess interactions with AMD genotype.

Design: Retrospective analysis of 2 controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2.

Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism.

Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages of aging and in rod regulatory regions, and some of these cluster at chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome.

Adherence to a Mediterranean diet and cognitive function in the Age-Related Eye Disease Studies 1 & 2.

Introduction: The objective was to determine whether closer adherence to the alternative Mediterranean Diet (aMED) was associated with altered cognitive function.

Methods: Observational analyses of participants (n = 7,756) enrolled in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2.

Results: Odds ratios for cognitive impairment, in aMED tertile 3 (vs 1), were 0.

No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18.

Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2).

Design: Post hoc analysis of a randomized trial.

Participants: White AREDS2 participants.

Age-related changes of the retinal microvasculature.

Purpose: Blood vessels of the retina provide an easily-accessible, representative window into the condition of microvasculature. We investigated how retinal vessel structure captured in fundus photographs changes with age, and how this may reflect features related to patient health, including blood pressure.

Results: We used two approaches.

Hyperreflective foci on optical coherence tomography associate with treatment outcome for anti-VEGF in patients with diabetic macular edema.

Purpose: To investigate the relationship between baseline number of hyperreflective foci (HF) on spectral domain optical coherence tomography (SD-OCT) in patients with diabetic macular edema (DME), as well as the dynamics of HF during treatment with anti-vascular endothelial growth factor (VEGF), and treatment response.

Methods: We evaluated patients diagnosed with DME scheduled for treatment with intravitreal bevacizumab. Eyes were classified as adequate or insufficient treatment responders based on logMAR visual acuity improvement and central retinal thickness (CRT) decrease after three consecutive injections.

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus.

Purpose: To investigate risk factors for the development and progression of diabetic retinopathy (DR) and long-term visual outcomes in Dutch patients with type 1 diabetes mellitus (T1DM).

Methods: Cumulative incidences were calculated for DR, vision-threatening DR (VTDR), defined as (pre)proliferative DR and diabetic macular oedema, and best-corrected visual acuity (BCVA) <0.5 and <0.

Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17.

Purpose: To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD).

Design: Retrospective analysis of a prospective cohort study.

Participants: Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection.

ADALIMUMAB THERAPY FOR REFRACTORY BIRDSHOT CHORIORETINOPATHY.

Purpose: To report the outcome of using adalimumab to treat birdshot chorioretinopathy.

Methods: Retrospective case series of 19 patients (38 eyes) with HLA-A29-positive birdshot chorioretinopathy who received adalimumab treatment. Patients had been refractory to previous standard systemic immunomodulatory therapy.

Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16.

Purpose: To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement.

Design: Prospective cohort study within a controlled clinical trial.

Participants: Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50-85 years.

Association of Genetic Variants With Response to Anti-Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration.

Importance: Visual acuity (VA) outcomes differ considerably among patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Identification of pharmacogenetic associations may help clinicians understand the mechanisms underlying this variability as well as pave the way for personalized treatment in nAMD.

Objective: To identify genetic factors associated with variability in the response to anti-VEGF therapy for patients with nAMD.

The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration-A cost-effectiveness analysis from a societal perspective.

Background: The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept.

Deep learning approach for the detection and quantification of intraretinal cystoid fluid in multivendor optical coherence tomography.

We developed a deep learning algorithm for the automatic segmentation and quantification of intraretinal cystoid fluid (IRC) in spectral domain optical coherence tomography (SD-OCT) volumes independent of the device used for acquisition. A cascade of neural networks was introduced to include prior information on the retinal anatomy, boosting performance significantly. The proposed algorithm approached human performance reaching an overall Dice coefficient of 0.

Improvement in activities of daily living after visual training in patients with homonymous visual field defects using Goal Attainment Scaling.

Background: Stroke is the most common cause of homonymous visual field defects (HVFDs). Yet, there is no standard protocol for composing a rehabilitation program.

Objective: In this study we assess ADL gain of visual training for vision restoration in HVFD patients by means of Goal Attainment Scaling.

Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.

Purpose: To investigate the association of rare predicted loss-of-function (pLoF) variants within age-related macular degeneration (AMD) risk loci and AMD sub-phenotypes.

Design: Case-control study.

Participants: Participants of AREDS, AREDS2, and Michigan Genomics Initiative.

A Deep Phenotype Association Study Reveals Specific Phenotype Associations with Genetic Variants in Age-related Macular Degeneration: Age-Related Eye Disease Study 2 (AREDS2) Report No. 14.

Purpose: Age-related macular degeneration (AMD), a multifactorial disease with variable phenotypic presentation, was associated with 52 single nucleotide polymorphisms (SNPs) at 34 loci in a genome-wide association study (GWAS). These genetic variants could modulate different biological pathways involved in AMD, contributing to phenotypic variability. To better understand the effects of these SNPs, we performed a deep phenotype association study (DeePAS) in the Age-Related Eye Disease Study 2 (AREDS2), followed by replication using AREDS participants, to identify genotype associations with AMD and non-AMD ocular and systemic phenotypes.

Automated Staging of Age-Related Macular Degeneration Using Optical Coherence Tomography.

Purpose: To evaluate a machine learning algorithm that automatically grades age-related macular degeneration (AMD) severity stages from optical coherence tomography (OCT) scans.

Methods: A total of 3265 OCT scans from 1016 patients with either no signs of AMD or with signs of early, intermediate, or advanced AMD were randomly selected from a large European multicenter database. A machine learning system was developed to automatically grade unseen OCT scans into different AMD severity stages without requiring retinal layer segmentation.

GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration.

Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated neovascular age-related macular degeneration (nAMD) patients. We performed pooled DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina 4.3 M array.

Visual Rehabilitation in Chronic Cerebral Blindness: A Randomized Controlled Crossover Study.

The treatment of patients suffering from cerebral blindness following stroke is a topic of much recent interest. Several types of treatment are under investigation, such as substitution with prisms and compensation training of saccades. A third approach, aimed at vision restitution is controversial, as a proper controlled study design is missing.