Background/Objective: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the primary treatment for neovascular AMD. This study aimed to assess racial, ethnic, and gender representation in U.S.-based randomized controlled trials (RCTs) of anti-VEGF therapies. Methods: A systematic PubMed search identified 19 eligible RCTs. Titles and abstracts were screened, and demographic data were independently extracted and cross-verified. Chi-squared analysis was used to evaluate disparities in participant representation. Risk of bias was assessed using the ROBIS checklist. Results: Among 8003 participants across 19 trials, 92.3% were Caucasian. Asian, African American, Hispanic/Latino, and American Indian participants collectively comprised just over 5%. This underrepresentation of non-Caucasian groups was statistically significant (p < 0.01, df = 4) and not associated with study sponsorship. Gender analysis showed 59% female and 41% male participation, which was not statistically significant (p = 0.83, df = 1). Conclusions: Non-Caucasian populations remain significantly underrepresented in anti-VEGF RCTs for AMD. This raises concerns about the generalizability of trial findings to diverse populations. Future clinical trials must prioritize inclusive recruitment to ensure equitable, evidence-based care for all patients.

Background and Objective: Keratoconus (KC) is a progressive corneal ectatic disorder characterized by progressive corneal stromal thinning, irregular steeping, and resultant visual impairment. The disease arises from a multifactorial interplay between genetic, biomechanical, biological, environmental, oxidative stressors, and ocular inflammatory factors. Advances in imaging modalities have allowed for earlier detection of subclinical disease, while emerging extracellular matrix (ECM) biomarkers [e.g., lysyl oxidase (LOX), matrix metalloproteinase-9 (MMP-9), procollagen C-proteinase enhancer (PCPE)] offer promise for improved disease monitoring and prognostication. Additionally, recent integration of artificial intelligence (AI) and machine learning technologies with corneal imaging and biological data shows promising enhanced diagnostic precision. Therapeutically, corneal collagen crosslinking (CXL) remains the gold standard for halting disease progression, with novel transepithelial CXL techniques, topography-guided photorefractive keratectomy (PRK), and intracorneal ring implantation continuing to expand treatment options. This review aimed to provide a comprehensive updated review of the pathophysiology of KC, to allow continued optimization of individual patient management and improve long term outcomes in KC. Methods: This narrative review was conducted using a literature search in PubMed. Articles were published in English between 2023 and 2025. Emphasis was placed on recent advances in pathophysiology of KC, diagnostics, and management options. Key Content and Findings: Recent literature highlights significant progress in understanding the molecular and structural basis of KC. New imaging technologies—including high-resolution corneal tomography and biomechanical assessment tools—enable earlier and more accurate detection of subclinical KC. The identification of tear-film and stromal biomarkers, including LOX and MMP-9, supports the development of non-invasive diagnostic and prognostic strategies. Additionally, AI-driven models that integrate imaging and molecular data have demonstrated improved sensitivity and specificity in early diagnosis compared to current technologies. From a therapeutic perspective, refinements in CXL protocols, including accelerated and transepithelial techniques, have enhanced safety and patient comfort while maintaining efficacy. Thus, combined approaches offer promising results in visual rehabilitation and disease stabilization. Conclusions: Overall, the convergence of genomics, proteomics, and computational modeling highlights the transition toward a future of precision-based, individualized, KC management. Continued integration of these new innovations will help to continue improving early detection, risk stratification, and personal treatment strategies.

Background and Objective: Glaucoma is a group of optic neuropathies that are characterized by progressive retinal ganglion cell (RGC) death and visual field loss. Most commonly, glaucoma progression is associated with elevated intraocular pressures (IOP); however, RGC injury and visual field loss have been observed in eyes at physiological IOP. This suggests that IOP-independent mechanisms may contribute to the pathophysiology of disease, most notably in patients with “normal” IOP values. Normal tension glaucoma (NTG) has demonstrated this multifactorial pathophysiology, with both IOP-dependent and IOP-independent disease progression. IOP-independent factors that have been identified include potential vascular autoregulation, aberrant translaminar pressure gradients, neurodegeneration, and pathological extracellular matrix (ECM) remodeling within the trabecular meshwork (TM). Though several IOP-independent factors exist, this narrative review focuses on the role that ECM dysregulation plays in optic nerve head (ONH) stress and ultimate RGC death. Methods: To better understand this, a structured literature review was conducted using PubMed, Google Scholar, and academic textbooks, covering English-language publications from 1986 to 2025. Studies were identified using keywords related to “normal tension glaucoma”, “extracellular matrix”, “juxtacanalicular”, and “genetics”, with screening of titles, abstracts, and full texts performed according to relevance to IOP-independent mechanisms of NTG. Key Content and Findings: Collectively, these findings support a paradigm in which NTG represents a distinct, IOP-independent pathophysiology, highlighting ECM biology and genetic regulation as potential therapeutic targets beyond conventional pressure-lowering strategies. Conclusions: Aberrant ECM remodeling—including fibrotic stiffening and TM cellular degeneration—may contribute to alterations in biomechanical signaling, resulting in non-measurable pressure transmission posteriorly to the ONH. This results in insidious ONH damage at physiological IOP. Molecular contributors have been identified to be contributory to this shift towards a fibrotic phenotype within the ECM, including upregulation of α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and N-cadherin, and downregulation of anti-fibrotic regulators (SERPINF1 and CHI3L1). Genetic and epigenetic factors—including variants of OPTN, TBK1, MYOC, and METTL23—have also been shown to play a role. This indicates that these genetic and epigenetic anomalies may be involved in the decreased neuroprotection, increased predilection for autophagy, and subsequent ECM remodeling seen at physiologic IOP values in NTG patients.