ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.

Objective: This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).

Design: ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).

Subjects: Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled.

Fluorescein CorneoGraphy (FCG): Use of a repurposed fluorescein imaging technique to objectively standardize corneal staining.

Punctate epithelial erosion (PEE) is a corneal sign of dry eye disease (DED), which is observable via staining with fluorescein on slit lamp as a standard of clinical practice and clinical research. There are currently many limitations for detecting PEE, such as lack of optimal excitation with cobalt blue light, difficulty to focus on the whole cornea, observer dependency and no available automatized quantification. We propose to reduce these limitations through repurposing the use of fluorescein angiography mode of optical coherence tomography (OCT, Heidelberg Spectralis II, Germany), as “fluorescein corneography” (FCG) for imaging PEE.

Phase 1 Clinical Trial of Elamipretide in Intermediate Age-Related Macular Degeneration and High-Risk Drusen: ReCLAIM High-Risk Drusen Study.

Purpose: To assess safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with intermediate age-related macular degeneration (AMD) and high-risk drusen (HRD) and to perform exploratory analyses of change in visual function.

Design: Phase 1, single-center, open-label, 24-week clinical trial with preplanned HRD cohort.

Participants: Adult patients ≥55 years of age with intermediate AMD and HRD.

Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration and Noncentral Geographic Atrophy: ReCLAIM NCGA Study.

Purpose: Assess the safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with dry age-related macular degeneration (AMD) and noncentral geographic atrophy (NCGA) and to perform exploratory analyses of change in visual function.

Design: Phase 1, single-center, open-label, 24-week clinical trial with preplanned NCGA cohort.

Participants: Adults ≥ 55 years of age with dry AMD and NCGA.

Incidence of Referable Retinal Disease in Diabetic Patients at a Primary Care Practice.

Purpose: This work tests the feasibility of remote ophthalmic imaging to identify referable retinal abnormalities and assesses the effectiveness of color fundus photography (CFP) vs optical coherence tomography (OCT) for this purpose.

Methods: This prospective, nonrandomized study included 633 patients with diabetes at Duke Primary Care. Undilated patients underwent screening with CFP and OCT camera (MaestroCare, Topcon).

Immunological Aspects of Age-Related Macular Degeneration.

Increasing evidence over the past two decades points to a pivotal role for immune mechanisms in age-related macular degeneration (AMD) pathobiology. In this chapter, we will explore immunological aspects of AMD, with a specific focus on how immune mechanisms modulate clinical phenotypes of disease and severity and how components of the immune system may serve as triggers for disease progression in both dry and neovascular AMD. We will briefly review the biology of the immune system, defining the role of immune mechanisms in chronic degenerative disease and differentiating from immune responses to acute injury or infection.

Cerebral white matter connectivity, cognition, and age-related macular degeneration.

Age-related macular degeneration (AMD) is a common retina disease associated with cognitive impairment in older adults. The mechanism(s) that account for the link between AMD and cognitive decline remain unclear. Here we aim to shed light on this issue by investigating whether relationships between cognition and white matter in the brain differ by AMD status.

Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities.

Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy.

Deep learning-based single-shot prediction of differential effects of anti-VEGF treatment in patients with diabetic macular edema.

Anti-vascular endothelial growth factor (VEGF) agents are widely regarded as the first line of therapy for diabetic macular edema (DME) but are not universally effective. An automatic method that can predict whether a patient is likely to respond to anti-VEGF therapy can avoid unnecessary trial and error treatment strategies and promote the selection of more effective first-line therapies. The objective of this study is to automatically predict the efficacy of anti-VEGF treatment of DME in individual patients based on optical coherence tomography (OCT) images.

Aldosterone as a mediator of severity in retinal vascular disease: Evidence and potential mechanisms.

Diabetic retinopathy (DR) and retinal vein occlusion (RVO) are the two most common retinal vascular diseases and are major causes of vision loss and blindness worldwide. Recent and ongoing development of medical therapies including anti-vascular endothelial growth factor and corticosteroid drugs for treatment of these diseases have greatly improved the care of afflicted patients. However, severe manifestations of retinal vascular disease result in persistent macular edema, progressive retinal ischemia and incomplete visual recovery.

Evaluation of a Remote Diagnosis Imaging Model vs Dilated Eye Examination in Referable Macular Degeneration.

Importance: In improving clinical outcomes, developing a sustainable, transformative care delivery model is important for accessible, efficient, low-cost, high-quality community-based imaging and diagnosis of retinal diseases.

Objective: To test the feasibility and accuracy of the remote diagnosis imaging model as a clinical screening tool to facilitate the identification of referable macular degeneration.

Design, Setting, And Participants: A nonrandomized study of 159 patients was conducted in sites with a relatively high disease prevalence (Duke University Health System endocrinology clinic and 2 Duke University Health System assisted living centers in North Carolina).

Longitudinal Study of Visual Function in Dry Age-Related Macular Degeneration at 12 Months.

Purpose: To report the 1-year progression of visual impairment on psychophysical tests of visual function in patients with early and intermediate age-related macular degeneration (AMD).

Design: Prospective, observational study.

Participants: Patients with early and intermediate AMD were enrolled from the existing population at the Duke Eye Center, and healthy age-matched control participants were recruited from family members or friends of the AMD patients and from the Duke Optometry and Comprehensive Eye Clinics.

Relating Sensory, Cognitive, and Neural Factors to Older Persons' Perceptions about Happiness: An Exploratory Study.

Despite increased rates of disease, disability, and social losses with aging, seniors consistently report higher levels of subjective well-being (SWB), a construct closely related to happiness, than younger adults. In this exploratory study, we utilized an available dataset to investigate how aspects of health commonly deteriorating with age, including sensory (i.e.

Aldosterone Exposure Causes Increased Retinal Edema and Severe Retinopathy Following Laser-Induced Retinal Vein Occlusion in Mice.

Purpose: To determine the effects of aldosterone exposure on retinal edema and retinopathy in a mouse model of retinal vein occlusion (RVO).

Methods: RVO was induced immediately following intravenous injection of Rose bengal (66 mg/kg) using a 532-nm wavelength laser to place three to seven applications at 80 mW and 50-μm spot size directed at the superior retinal vein one disc diameter away from the nerve. Negative control consisted of placing an equal number of laser spots without targeting the vein.

Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints.

Purpose: To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD.

Design: Cross-sectional analysis of baseline data from a prospective study.

Methods: One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls.

Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer's disease.

Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults.

Association of Low Luminance Questionnaire With Objective Functional Measures in Early and Intermediate Age-Related Macular Degeneration.

Purpose: To determine whether Low Luminance Questionnaire (LLQ) scores are associated with objective measures of visual function in early and intermediate age-related macular degeneration (AMD).

Methods: Cross-sectional study of subjects with early AMD Age-Related Eye Disease Study (AREDS) stage 2, N = 33), intermediate AMD (AREDS stage 3, N = 47), and age-matched healthy controls (N = 21). Subjects were interviewed with the LLQ.

Language processing in age-related macular degeneration associated with unique functional connectivity signatures in the right hemisphere.

Age-related macular degeneration (AMD) is a retinal disease associated with significant vision loss among older adults. Previous large-scale behavioral studies indicate that people with AMD are at increased risk of cognitive deficits in language processing, particularly in verbal fluency tasks. The neural underpinnings of any relationship between AMD and higher cognitive functions, such as language processing, remain unclear.

A Quantitative Approach to Predict Differential Effects of Anti-VEGF Treatment on Diffuse and Focal Leakage in Patients with Diabetic Macular Edema: A Pilot Study.

Purpose: We use semiautomated segmentation of fluorescein angiography (FA) to determine whether anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) differentially affects microaneurysm (MA)-associated leakage, termed focal leakage, versus non-MA-associated leakage, termed diffuse leakage.

Methods: We performed a retrospective study of 29 subjects treated with at least three consecutive injections of anti-VEGF agents for DME (mean 4.6 injections; range, 3-10) who underwent Heidelberg FA before and after anti-VEGF therapy.

Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: We assess the effect of intravitreal anti-VEGF injections on tonographic outflow facility.

Methods: Patients with age-related macular degeneration who had received unilateral intravitreal anti-VEGF injections were recruited into two groups, those with ≤10 and those with ≥20 total anti-VEGF injections. Intraocular pressure and tonographic outflow facility of injected and uninjected fellow eyes were measured and compared between groups.

Enhanced visualization of peripheral retinal vasculature with wavefront sensorless adaptive optics optical coherence tomography angiography in diabetic patients.

Optical coherence tomography angiography (OCTA) is a promising technique for non-invasive visualization of vessel networks in the human eye. We debut a system capable of acquiring wide field-of-view (>70°) OCT angiograms without mosaicking. Additionally, we report on enhancing the visualization of peripheral microvasculature using wavefront sensorless adaptive optics (WSAO).

Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy.

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented.

Screening for Diabetic Retinopathy Using a Portable, Noncontact, Nonmydriatic Handheld Retinal Camera.

Background: Diabetic retinopathy (DR) is a leading cause of low vision and blindness. We evaluated the feasibility of using a handheld, noncontact digital retinal camera, Pictor, to obtain retinal images in dilated and undilated eyes for DR screening. We also evaluated the accuracy of ophthalmologists with different levels of training/experience in grading these images to identify eyes with vision-threatening DR.

Semiautomatic Segmentation of Rim Area Focal Hyperautofluorescence Predicts Progression of Geographic Atrophy Due to Dry Age-Related Macular Degeneration.

Purpose: To develop image analysis software usable by nonexpert graders to segment geographic atrophy (GA) from dry AMD and to quantify rim area focal hyperautofluorescence (RAFH) surrounding GA on fundus autofluorescence (FAF) images. To compare the GA progression predictions based on RAFH with those of a validated qualitative classification system.

Methods: Retrospective analysis of serial FAF images from 49 eyes of 30 subjects with GA was performed using MATLAB-based software (MathWorks, Natick, MA, USA).

Forming a Consensus: Data and Guidance for Physicians Treating Diabetic Macular Edema.

The diabetic macular edema (DME) treatment paradigm has evolved as the understanding of the disease pathology has grown. Since 2012, four pharmacotherapies have been approved by the U.S.