Endothelial keratoplasty (EK), including Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty, is now the most performed corneal transplant procedure in the United States. Intraocular pressure (IOP) elevation and glaucoma are common complications and can cause irreversible vision loss and corneal graft failure. This review will cover the incidence, risk factors, and management of glaucoma and IOP elevation after EK. Higher preoperative IOP, preoperative glaucoma, and certain indications for EK, such as bullous keratopathy, are associated with increased risk of glaucoma and glaucoma progression in patients undergoing EK. In addition, we summarize the studies assessing graft outcomes in EK patients with glaucoma or glaucoma surgery. Finally, we provide future directions to improve clinical care in EK patients with glaucoma.

INTRODUCTION: We describe a novel technique for identifying endothelial Descemet membrane (DM) tags remaining after descemetorhexis in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A surgical goniolens is applied to the corneal surface after descemetorhexis in order to visualize the peripheral inner corneal layer at 360° and identify endothelial-DM tags. RESULTS: A detailed visualization of the peripheral inner corneal layer is possible using goniolens, without using any staining in the anterior chamber. CONCLUSION: The technique may be used to screen the posterior corneal surface for any retained endothelial-DM tags. It may to lower the risk of remaining tags and indirectly lower the incidence of DMEK graft detachment.

IMPORTANCE: Despite persistent inequalities in access to eye care services globally, guidance on a set of recommended, evidence-based eye care interventions to support country health care planning has not been available. To overcome this barrier, the World Health Organization (WHO) Package of Eye Care Interventions (PECI) has been developed. OBJECTIVE: To describe the key outcomes of the PECI development. EVIDENCE REVIEW: A standardized stepwise approach that included the following stages: (1) selection of priority eye conditions by an expert panel after reviewing epidemiological evidence and health facility data; (2) identification of interventions and related evidence for the selected eye conditions from a systematic review of clinical practice guidelines (CPGs); stage 2 included a systematic literature search, screening of title and abstracts (excluding articles that were not relevant CPGs), full-text review to assess disclosure of conflicts of interest and affiliations, quality appraisal, and data extraction; (3) expert review of the evidence extracted in stage 2, identification of missed interventions, and agreement on the inclusion of essential interventions suitable for implementation in low- and middle-income resource settings; and (4) peer review. FINDINGS: Fifteen priority eye conditions were chosen. The literature search identified 3601 articles. Of these, 469 passed title and abstract screening, 151 passed full-text screening, 98 passed quality appraisal, and 87 were selected for data extraction. Little evidence (≤1 CPG identified) was available for pterygium, keratoconus, congenital eyelid disorders, vision rehabilitation, myopic macular degeneration, ptosis, entropion, and ectropion. In stage 3, domain-specific expert groups voted to include 135 interventions (57%) of a potential 235 interventions collated from stage 2. After synthesis across all interventions and eye conditions, 64 interventions (13 health promotion and education, 6 screening and prevention, 38 treatment, and 7 rehabilitation) were included in the PECI. CONCLUSIONS AND RELEVANCE: This systematic review of CPGs for priority eye conditions, followed by an expert consensus procedure, identified 64 essential, evidence-based, eye care interventions that are required to achieve universal eye health coverage. The review identified some important gaps, including a paucity of high-quality, English-language CPGs, for several eye diseases and a dearth of evidence-based recommendations on eye health promotion and prevention within existing CPGs.

Despite rigorous investigations, the hydrogels currently available to replace damaged tissues, such as the cornea, cannot fulfill mechanical and structural requirements and, more importantly, cannot be sutured into host tissues due to the lack of hierarchical structures to dissipate exerted stress. In this report, solution electrospinning of polycaprolactone (PCL), protein-based hydrogel perfusion, and layer-by-layer stacking are used to generate a hydrogel-microfiber composite with varying PCL fiber diameters and hydrogel concentrations. Integrating PCL microfibers into the hydrogel synergistically improves the mechanical properties and suturability of the construct up to 10-fold and 50-fold, respectively, compared to the hydrogel and microfiber scaffolds alone, approaching those of the corneal tissue. Human corneal cells cultured on composites are viable and can spread, proliferate, and retain phenotypic characteristics. Moreover, corneal stromal cells migrate into the scaffold, degrade it, and regenerate the extracellular matrix. The current hydrogel reinforcing system paves the way for producing suturable and, therefore, transplantable tissue constructs with desired mechanical properties.

A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the PDE6B gene in the affected twins and their unaffected father. Further investigation, using genome sequencing, identified a novel ∼7.5-kb deletion (Chr 4:670,405-677,862del) encompassing the ATP5ME gene, part of the 5' UTR of MYL5, and a 378-bp (Chr 4:670,405-670,782) region from the 3' UTR of PDE6B in the affected twins and their unaffected mother. Both variants segregated with disease in the family. Analysis of the relative expression of PDE6B, in peripheral blood cells, also revealed a significantly lower level of PDE6B transcript in affected siblings compared to a normal control. PDE6B is associated with recessive rod-cone degeneration and autosomal dominant congenital stationary night blindness. Ophthalmic evaluation of these patients showed night blindness, fundus abnormalities, and peripheral vision loss, which are consistent with PDE6B-associated recessive retinal degeneration. These findings suggest that the loss of PDE6B transcript resulting from the compound heterozygous pathogenic variants is the underlying cause of recessive rod-cone degeneration in the study family.

PURPOSE: To evaluate the efficacy of topical netarsudil 0.02% as adjunctive therapy in children with refractory pediatric glaucoma. METHODS: The medical records of patients ≤18 years diagnosed with pediatric glaucoma treated with topical netarsudil 0.02% from June 2019 to March 2022 were reviewed retrospectively. Data collected included age, sex, ethnicity, etiology of glaucoma, history of previous or subsequent glaucoma surgery, and intraocular pressure (IOP) before and after the addition of topical netarsudil. RESULTS: A total of 21 eyes of 16 patients (11 males) were included. Five patients used topical netarsudil in both eyes. Eight patients were Hispanic. The mean number of glaucoma surgeries and medications before initiating topical netarsudil was 1.8 ± 1.2 and 3.7 ± 0.5, respectively. The mean age prior to starting topical netarsudil was 8.9 ± 4.1 years. The mean follow-up after initiating topical netarsudil was 11.3 ± 8.2 months. The IOP was significantly reduced from 26.3 ± 6.2 mm Hg before topical netarsudil to 19.6 ± 6.02 mm Hg at 1 month in 15 eyes (P < 0.01), 18.2 ± 6.9 mm Hg at 3-months in 18 eyes (P < 0.01), 18.3 ± 7.3 mm Hg at 6 months in 13 eyes (P = 0.01), 17.6 ± 5.07 mm Hg at 9 months in 14 eyes (P = 0.002), and 17.4 ± 3.1 mm Hg at 12 months in 13 eyes (P = 0.002). Nine eyes (43%) underwent additional glaucoma surgery due to long-term failure of topical netarsudil to reduce IOP despite an initial reduction, and one eye had persistent IOP elevation ≥21 mm Hg despite the addition of topical netarsudil. CONCLUSIONS: In our small cohort of patients with refractory pediatric glaucoma, the addition of topical netarsudil reduced IOP, potentially delaying the need for surgery.

How to deliver best care in various clinical settings remains a vexing problem. All pertinent healthcare-related questions have not, cannot, and will not be addressable with costly time- and resource-consuming controlled clinical trials. At present, evidence-based guidelines can address only a small fraction of the types of care that clinicians deliver. Furthermore, underserved areas rarely can access state-of-the-art evidence-based guidelines in real-time, and often lack the wherewithal to implement advanced guidelines. Care providers in such settings frequently do not have sufficient training to undertake advanced guideline implementation. Nevertheless, in advanced modern healthcare delivery environments, use of eActions (validated clinical decision support systems) could help overcome the cognitive limitations of overburdened clinicians. Widespread use of eActions will require surmounting current healthcare technical and cultural barriers and installing clinical evidence/data curation systems. The authors expect that increased numbers of evidence-based guidelines will result from future comparative effectiveness clinical research carried out during routine healthcare delivery within learning healthcare systems.

PURPOSE: To present a literature review on various immunopathologic dysfunctions following COVID-19 infection and their potential implications in development of rhino-orbital-cerebral mucormycosis (ROCM). METHODS: A literature search was performed via Google Scholar and PubMed with subsequent review of the accompanying references. Analogies were drawn between the immune and physiologic deviations caused by COVID-19 and the tendency of the same to predispose to ROCM. RESULTS: Sixty-two articles were reviewed. SARS-CoV-2 virus infection leads to disruption of epithelial integrity in the respiratory passages, which may be a potential entry point for the ubiquitous Mucorales to become invasive. COVID-19 related GRP78 protein upregulation may aid in spore germination and hyphal invasion by Mucorales. COVID-19 causes interference in macrophage functioning by direct infection, a tendency for hyperglycemia, and creation of neutrophil extracellular traps. This affects innate immunity against Mucorales. Thrombocytopenia and reduction in the number of natural killer (NK) cells and infected dendritic cells is seen in COVID-19. This reduces the host immune response to pathogenic invasion by Mucorales. Cytokines released in COVID-19 cause mitochondrial dysfunction and accumulation of reactive oxygen species, which cause oxidative damage to the leucocytes. Hyperferritinemia also occurs in COVID-19 resulting in suppression of the hematopoietic proliferation of B- and T-lymphocytes. CONCLUSIONS: COVID-19 has a role in the occurrence of ROCM due to its effects at the entry point of the fungus in the respiratory mucosa, effects of the innate immune system, creation of an environment of iron overload, propagation of hyperglycemia, and effects on the adaptive immune system.

PURPOSE: To report practice patterns of intravitreal injections of anti-VEGF for retinopathy of prematurity (ROP) and outcomes data with a focus on retreatments and complications. DESIGN: Multicenter, international, retrospective, consecutive series. SUBJECTS: Patients with ROP treated with anti-VEGF injections from 2007 to 2021. METHODS: Twenfty-three sites (16 United States [US] and 7 non-US) participated. Data collected included demographics, birth characteristics, examination findings, and methods of injections. Comparisons between US and non-US sites were made. MAIN OUTCOME MEASURES: Primary outcomes included number and types of retreatments as well as complications. Secondary outcomes included specifics of the injection protocols, including types of medication, doses, distance from limbus, use of antibiotics, and quadrants where injections were delivered. RESULTS: A total of 1677 eyes of 918 patients (43% female, 57% male) were included. Mean gestational age was 25.7 weeks (range, 21.2-41.5 weeks), and mean birth weight was 787 g (range, 300-2700 g). Overall, a 30-gauge needle was most commonly used (51%), and the quadrant injected was most frequently the inferior-temporal (51.3%). The distance from the limbus ranged from 0.75 to 2 mm, with 1 mm being the most common (65%). Bevacizumab was the most common anti-VEGF (71.4%), with a dose of 0.625 mg in 64% of cases. Overall, 604 (36%) eyes required retreatment. Of those, 79.8% were retreated with laser alone, 10.6% with anti-VEGF injection alone, and 9.6% with combined laser and injection. Complications after anti-VEGF injections occurred in 15 (0.9%) eyes, and no cases of endophthalmitis were reported. Patients in the United States had lower birth weights and gestational ages (665.6 g and 24.5 weeks, respectively) compared with non-US patients (912.7 g and 26.9 weeks, respectively) (P < 0.0001). Retreatment with reinjection and laser was significantly more common in the US compared with the non-US group (8.5% vs. 4.7% [P = 0.0016] and 55% vs. 7.2% [P < 0.001], respectively). There was no difference in the incidence of complications between the 2 geographic subgroups. CONCLUSIONS: Anti-VEGF injections for ROP were safe and well tolerated despite a variance in practice patterns. Infants with ROP receiving injections in the US tended to be younger and smaller, and they were treated earlier with more retreatments than non-US neonates with ROP.

Proliferative vitreoretinopathy (PVR) is a fibrotic eye disease that develops after rhegmatogenous retinal detachment surgery and open-globe traumatic injury. Idelalisib is a specific inhibitor of phosphoinositide 3-kinase (PI3K) δ. While PI3Kδ is primarily expressed in leukocytes, its expression is also considerably high in retinal pigment epithelial (RPE) cells, which play a crucial part in the PVR pathogenesis. Herein we show that GeoMx Digital Spatial Profiling uncovered strong expression of fibronectin in RPE cells within epiretinal membranes from patients with PVR, and that idelalisib (10 μM) inhibited Akt activation, fibronectin expression and collagen gel contraction induced by transforming growth factor (TGF)-β2 in human RPE cells. Furthermore, we discovered that idelalisib at a vitreal concentration of 10 μM, a non-toxic dose to the retina, prevented experimental PVR induced by intravitreally injected RPE cells in rabbits assessed by experienced ophthalmologists using an indirect ophthalmoscope plus a + 30 D fundus lens, electroretinography, optical coherence tomography and histological analysis. These data suggested idelalisib could be harnessed for preventing patients from PVR.

PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = -2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.

Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment.

BACKGROUND: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described. PURPOSE: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED. METHODS: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated. FINDINGS: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development. CONCLUSION: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED.

OBJECTIVES: To analyze the top 100 cited papers on ophthalmic trauma. METHODS: A literature search of Ophthalmology journals within the ISI Web of Science database for the most cited papers related to ophthalmic trauma. RESULTS: The most cited articles were published between 1943 and 2013, the greatest number being published in 2000. Ophthalmology (45), Archives of Ophthalmology (17), and the American Journal of Ophthalmology (15) published most of the articles. The institutions with the highest number of publications were Wilmer Eye Institute (10) and Massachusetts Eye and Ear Infirmary (7). Sixty-seven percent of the articles originated from the USA. The most common type of trauma studied was non-open-globe injuries and the most frequent topic studied were pathological conditions secondary to trauma (34), particularly endophthalmitis (8), and optic neuropathy (6). Articles presenting a standardized classification system for eye injury received the highest average of citations per publication. Types of research most frequently cited were observational clinical studies (62) and epidemiological studies (30); the least frequent were clinical trials (2). CONCLUSION: This bibliographic study provides a historical perspective of the literature and identifies trends within the most highly influential papers on ophthalmic trauma. Many of these articles emerged within the past three decades and came from Ophthalmology journals that remain high impact to this day. Clinical trials have been difficult to conduct and are lacking, reflecting a critical need in ophthalmic trauma research, as most of our understanding of ophthalmic trauma comes from observational and epidemiological studies.

PURPOSE: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services' (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI). METHODS: This was a retrospective analysis of 2016-2019 clinical data (n = 53,900). UWF images were acquired by certified imagers using a validated protocol, and graded by licensed, certified optometrists supervised by an ophthalmologist. Graders evaluated the extent/severity of retinal lesions in comparison to standard photographs. DR lesions predominantly in any peripheral field were considered "predominantly peripheral lesions" (PPL). The analyses calculated prevalence of any DR, any DME, DR and DME severity, sight-threatening disease, and PPL. RESULTS: Patients averaged 56 years of age with a 68 mmol/mol A1c and 55% had had diabetes for 5+ years. Prevalence of any DR, any DME, and sight-threatening disease was 28.6%, 3.0%, and 3.0%. In patients with mild nonproliferative DR, PPL was seen in 25.3%. PPL suggested a more severe level of DR in 8.7% of patients. DR increased with age. DME decreased with age. Males and patients in the Nashville IHS area had more diabetic eye disease. CONCLUSION: AI/AN have a high burden of diabetes and its complications. The IHS is resource-constrained, making accurate disease estimates necessary for resource allocation and budget justifications to Congress. These data update the estimates of diabetic eye disease in Indian Country and suggest that UWFI identifies early DR.