Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs.

Inherited retinal degeneration (IRD) disease and age-related macular degeneration (AMD) are leading causes of irreversible vision loss and blindness. Although significant progress has advanced the field in the past 5 years, significant challenges remain. The current article reviews the accomplishments and research advances that have fueled the development of treatments for patients with IRD and AMD, including the first approved gene-augmentation treatment for RPE65-related retinal degeneration and complement inhibition therapies to slow progression of geographic atrophy (GA) in AMD.

OCT Changes Observed during the Progression of Early Age-Related Macular Degeneration.

Purpose: Automated retinal cell layer segmentation empowers OCT as a precise tool for characterizing morphologic features of retinal health throughout age-related macular degeneration (AMD) progression, particularly in advance of more visible biomarkers such as drusen and macular pigmentary changes. Few studies have examined OCT changes in eyes progressing from early to intermediate disease, or combined examinations of cell layer thickness, reflectivity, and heterogeneity. Therefore, this study analyzed OCTs from eyes progressing from early to intermediate AMD to identify changes in retinal morphology and reflectivity that may serve as biomarkers of early progression.

Neighborhood-Level Social Determinants of Health and Presenting Characteristics for Rhegmatogenous Retinal Detachments.

Importance: Functional outcomes after repair of rhegmatogenous retinal detachments (RRDs) are highly dependent on baseline visual acuity and foveal status. Adverse social determinants of health (SDOH) can present barriers to timely presentation for repair and limit vision outcomes.

Objective: To evaluate the association between neighborhood-level SDOH with baseline severity (visual acuity and fovea status) of RRD.

The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD.

Non-neovascular or dry age-related macular degeneration (AMD) is a multi-factorial disease with degeneration of the aging retinal-pigmented epithelium (RPE). Lysosomes play a crucial role in RPE health via phagocytosis and autophagy, which are regulated by transcription factor EB/E3 (TFEB/E3). Here, we find that increased AKT2 inhibits PGC-1α to downregulate SIRT5, which we identify as an AKT2 binding partner.

Risk Factors Associated with Cystoid Macular Edema among Patients Undergoing Primary Repair of Rhegmatogenous Retinal Detachment.

Purpose: To investigate predictors of the development and resolution of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair.

Design: Retrospective cross sectional study.

Subjects: Patients who underwent primary repair of uncomplicated RRD.

In-Depth Analysis of Preoperative OCT Markers as Prognostic Factors for Lamellar Macular Holes and Epiretinal Membrane Foveoschisis.

Objective: To identify preoperative OCT markers that correlate with postoperative visual acuity (VA) changes in eyes with lamellar macular hole (LMH) and epiretinal membrane foveoschisis (ERMF) after pars plana vitrectomy (PPV).

Design: Cross-sectional retrospective study.

Subjects: Patients seen at the Wilmer Eye Institute between 2011 and 2021 with an International Classification of Diseases, Ninth Revision, or International Classification of Diseases, 10th Revision, code for "macular hole" that underwent PPV, and demonstrated all OCT criteria present for either LMH or ERMF based on the Hubschman et al (2020) classification.

Significance of Social Determinants of Health in Tumor Presentation, Hospital Readmission, and Overall Survival in Ocular Oncology.

Purpose: To evaluate the association between social determinants of health (SDH) with presentation and outcomes in patients with ocular cancer.

Methods: The National Cancer Database was queried for primary clinical tumor (cT) classifications of T1 to T4 N0M0 uveal melanoma, conjunctival melanoma, or retinoblastoma diagnosed between January 2006 and December 2017. Pearson χ analysis assessed differences in SDH-related characteristics between cancer cohorts.

Lysosomes in retinal health and disease.

Lysosomes play crucial roles in various cellular processes - including endocytosis, phagocytosis, and autophagy - which are vital for maintaining retinal health. Moreover, these organelles serve as environmental sensors and act as central hubs for multiple signaling pathways. Through communication with other cellular components, such as mitochondria, lysosomes orchestrate the cytoprotective response essential for preserving cellular homeostasis.

The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in atrophic AMD.

Age-related macular degeneration (AMD), the leading cause of geriatric blindness, is a multi-factorial disease with retinal-pigmented epithelial (RPE) cell dysfunction as a central pathogenic driver. With RPE degeneration, lysosomal function is a core process that is disrupted. Transcription factors EB/E3 (TFEB/E3) tightly control lysosomal function; their disruption can cause aging disorders, such as AMD.

Thermal Shift Assay in Ferroptosis.

Ferroptosis is a recently described process of cell death that is dependent on unregulated cellular iron accumulation with induction of oxidative stress. Ferroptosis has been linked to several human diseases; therefore, investigations aimed at better understanding the pathway and elucidating avenues for future drug development are warranted. Current assays that target ferroptosis/oxidative stress in cells is limited to western blotting and imaging techniques, and unfortunately provide only a broad understanding that is insufficient to effectively assess novel drugs (ligands).

Using the language of surgery to enhance ophthalmology surgical education.

Background: Currently, surgical education utilizes a combination of the apprentice model, wet-lab training, and simulation, but due to reliance on subjective data, the quality of teaching and assessment can be variable. The "language of surgery," an established concept in engineering literature whose incorporation into surgical education has been limited, is defined as the description of each surgical maneuver using quantifiable metrics. This concept is different from the traditional notion of surgical language, generally thought of as the qualitative definitions and terminology used by surgeons.

A Clinical and Preclinical Assessment of Clinical Trials for Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness for the elderly in high-income countries. Although multivitamin antioxidant nutrients can slow the progression of intermediate "dry" or nonneovascular AMD, no treatment can halt or reverse any stage of dry disease. Multiple biologic pathways have been implicated in AMD pathobiology, including the complement pathway.

URINARY METABOLOMICS OF CENTRAL SEROUS CHORIORETINOPATHY.

Purpose: To analyze the urinary metabolomic profile of central serous chorioretinopathy cases.

Methods: In a cross-sectional study, 80 participants with central serous chorioretinopathy were compared with 80 age-matched and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4 platform.

Microglia-Neutrophil Interactions Drive Dry AMD-like Pathology in a Mouse Model.

In dry age-related macular degeneration (AMD), inflammation plays a key role in disease pathogenesis. Innate immune cells such as microglia and neutrophils infiltrate the sub-retinal space (SRS) to induce chronic inflammation and AMD progression. But a major gap in our understanding is how these cells interact with each other in AMD.

Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy.

The retinal pigment epithelium (RPE) plays an important role in the development of diabetic retinopathy (DR), a leading cause of blindness worldwide. Here we set out to explore the role of Akt2 signaling-integral to both RPE homeostasis and glucose metabolism-to DR. Using human tissue and genetically manipulated mice (including RPE-specific conditional knockout (cKO) and knock-in (KI) mice), we investigate whether Akts in the RPE influences DR in models of diabetic eye disease.

Symptom-Based Risk Factors for Retinal Tears and Detachments in Suspected Posterior Vitreous Detachment.

Introduction: The aim of this study was to determine symptom-level risk factors for retinal tear/retinal detachment (RT/RD) in our patients presenting with symptoms of posterior vitreous detachment (PVD).

Methods: We conducted a prospective cohort study of patients presenting to outpatient ophthalmology clinics at a single academic institution with complaint(s) of flashes, floaters, and/or subjective field loss (SFL). Patients received a standardized questionnaire regarding past ocular history and symptom characteristics including number, duration, and timing of flashes and floaters, prior to dilated ocular examination.

Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity.

Age-related macular degeneration (AMD), the leading cause of blindness among the elderly, is without treatment for early disease. Degenerative retinal pigment epithelial (RPE) cell heterogeneity is a well-recognized but understudied pathogenic factor. Due to the daily phagocytosis of photoreceptor outer segments, unique photo-oxidative stress, and high metabolism for maintaining vision, the RPE has robust macroautophagy/autophagy, and mitochondrial and antioxidant networks.

Socioeconomic disadvantage and impact on visual outcomes in patients with viral retinitis and retinal detachment.

While socioeconomic disparities impact clinical care and patient outcomes, their impact on the anatomic and visual outcomes of retinal detachment in patients with viral retinitis is unstudied. This case series included 18 eyes in 18 patients from a single academic institution between January 1, 2008 and December 31, 2018. Patient characteristics including age, sex, race, ethnicity, insurance, immunosuppression, viral retinitis, retinal detachment, retinal detachment repair, visual and anatomic outcomes, missed appointments, and Area Deprivation Index [ADI] were collected.

Visual acuity after cataract surgery in Macular Telangiectasia Type 2 Stage 3 to 5.

Background: The purpose of this study was to evaluate visual acuity after cataract surgery in eyes with Macular Telangiectasia (MacTel) Type 2.

Methods: Single-center retrospective cohort study of patients with MacTel Type 2 who underwent cataract surgery and were managed at the same institution. Patients underwent pre-operative assessment by a retinal specialist with examination and optical coherence tomography (OCT) at the same institution.

Characterization and identification of measurable endpoints in a mouse model featuring age-related retinal pathologies: a platform to test therapies.

Apolipoprotein B100 (apoB100) is the structural protein of cholesterol carriers including low-density lipoproteins. It is a constituent of sub-retinal pigment epithelial (sub-RPE) deposits and pro-atherogenic plaques, hallmarks of early dry age-related macular degeneration (AMD), an ocular neurodegenerative blinding disease, and cardiovascular disease, respectively. Herein, we characterized the retinal pathology of transgenic mice expressing mouse apoB100 in order to catalog their functional and morphological ocular phenotypes as a function of age and establish measurable endpoints for their use as a mouse model to test potential therapies.

Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.

In dry age-related macular degeneration (AMD), LCN2 (lipocalin 2) is upregulated. Whereas LCN2 has been implicated in AMD pathogenesis, the mechanism remains unknown. Here, we report that in retinal pigmented epithelial (RPE) cells, LCN2 regulates macroautophagy/autophagy, in addition to maintaining iron homeostasis.

Management of uncomplicated rhegmatogenous retinal detachments: a comparison of practice patterns and clinical outcomes in a real-world setting.

Objective: To investigate practice patterns and clinical outcomes in the repair of uncomplicated rhegmatogenous retinal detachments (RRD) in a real-world setting over a 10-year period.

Methods: We compared preferences for scleral buckling (SB), pars plana vitrectomy (PPV), PPV/SB, or pneumatic retinopexy (PR) over time, and examined the 1-year single surgery anatomic success (SSAS) and best-corrected visual acuity (BCVA) at a tertiary academic institution from 2008-2018.

Results: Eight hundred eight eyes had RRD repair between 2008-2011 (n = 240), 2012-2014 (n = 271), and 2015-2017 (n = 297).