Effect of Head Trauma-Related Deaths on Corneal Endothelial Cell Loss in Eye Bank Donors.

PURPOSE: The purpose of this study was to examine the effect of head trauma-related deaths on corneal endothelial cell density (ECD) in eye bank donors. METHODS: This is a retrospective study of 287 corneas from donors with causes of death secondary to motor vehicle accident with sustained head trauma (n = 50), gunshot wound to the head (n = 138), fall with sustained head trauma (n = 2), and non-head-related traumatic causes of death (n = 97). Donors older than age 50 years were excluded due to concern for undiagnosed Fuchs endothelial dystrophy as a potential confounder for the cause of endothelial cell loss. Donor characteristics, ECD, and focal endothelial cell loss on specular microscopy were compared between the groups. Donors in the head trauma and nonhead trauma groups were matched by age; there were 42 age-matched donors in both groups. RESULTS: Age and ECD were negatively correlated (Pearson correlation coefficient = -0.57). Death-to-preservation time was not significantly different between the 2 groups ( P value = 0.59). The mean ECD in the head trauma group was 2859 ± 370 cells/mm 2 and 3041 ± 464 cells/mm 2 in the nonhead trauma group. The head trauma group had a lower ECD (178 ± 70 cells/mm 2 , P value = 0.013). After matching for age, the difference in ECD between the 2 groups was -94 ± 82 cells/mm 2 ( P value = 0.26). The adjusted odds of having focal endothelial cell loss was not statistically significant ( P value = 0.50) between the groups. CONCLUSIONS: After statistical adjustments, there were no differences between the head trauma and nonhead trauma groups.

National Access to EyeSi Simulation: A Comparative Study Among U.S. Ophthalmology Residency Programs.

Purpose The aim of this study was to evaluate regional disparities in access to EyeSi surgical simulation training among U.S. ophthalmology residency programs. Methods Access to EyeSi simulation was determined from sales data (2021) provided by VRMagic. Key demographic metrics of the primary counties of U.S. residency training programs were retrieved from the U.S. Census Bureau Database (2019) and PolicyMap (2021). Demographic metrics, Veterans Affairs (VA) hospital affiliation, and Doximity residency program ranking (2021) were compared using the Mann-Whitney U test and Fisher's exact test. Results A total of 124 residency training programs across 95 U.S. counties were included. Regional density (number of EyeSi simulators/million people) was calculated; the west had a significantly lower density when compared with the northeast (NE), south, and midwest (0.4 vs 1.0, 1.3, 1.1, respectively). In the NE, there was a significantly lower population of Blacks ( p = 0.01), Hispanics ( p = 0.028), and Native Americans ( p = 0.008) residing in counties with access to EyeSi, compared with counties without EyeSi access. Programs with EyeSi access ( N = 95) had a median Doximity ranking of 52.5, whereas programs without EyeSi access ( N = 35) had a lower median ranking of 94 ( p < 0.001). Conclusion Our analysis demonstrates significant disparities in access to EyeSi simulation training in the United States that could disproportionately impact minority communities. Access to an EyeSi simulator was associated with higher residency ranking independent of VA affiliation.

Changes in Rat Scleral Collagen Structure Induced by UVA-Riboflavin Crosslinking at Various Tissue Depths in Whole Globe Versus Scleral Patch.

Purpose: To investigate structural changes in scleral collagen fibers at various tissue depths before and after photosensitized crosslinking (CXL) both isolated scleral patch versus whole globe using second-harmonic generation (SHG) imaging. Methods: Scleral tissues were harvested from Sprague-Dawley rats and separated into three groups: untreated sclera (control), full-thickness scleral patch for CXL (Free Scleral CXL group), and sclera in intact globe for CXL (Globe CXL group). The CXL groups were soaked in 0.1% riboflavin and irradiated with 365 nm ultraviolet-A light (power, 0.45 mW/cm2) for 30 minutes. SHG images were acquired every 5 µm between 10 and 60 µm from the outer scleral surface. Collagen fiber waviness was calculated as the ratio of the total length of a traced fiber and the length of a straight path between the fiber ends. Results: In the Free Scleral CXL group, collagen waviness was significantly increased compared to the control group at 35 to 50 µm (P < 0.05). In the Globe CXL group, collagen waviness was decreased compared to control at all depths with statistical significance (P < 0.05) achieved from 10 to 45 µm. Conclusions: Depending upon its initial state (i.e., free scleral patch versus mechanically loaded intact globe under pressure), collagen may experience different structural changes after CXL. In addition, the extent of the CXL effects may vary at different depths away from the surface. Translational Relevance: Understanding the CXL effects on collagen structure may be important in optimizing the scleral crosslinking protocol for future clinical applications such as preventing myopic progression.

The Cost-Effectiveness of a Telemedicine Screening Program for Diabetic Retinopathy in New York City.

Background: A telemedicine screening initiative was implemented by the Montefiore Health System to improve access to eyecare for a multi-ethnic, at-risk population of diabetic patients in a largely underserved urban community in the Bronx, New York. This retrospective, cross-sectional analysis evaluates the societal benefit and financial sustainability of this program by analyzing both cost and revenue generation based on current standard Medicare reimbursement rates. Methods: Non-mydriatic fundus cameras were placed in collaboration with a vendor in eight outpatient primary care sites throughout the Montefiore Health Care System, and data was collected between June 2014 and July 2016. Fundus photos were electronically transmitted to a central reading center to be systematically reviewed and coded by faculty ophthalmologists, and patients were subsequently scheduled for ophthalmic evaluation based upon a predetermined treatment algorithm. A retrospective chart review of 2251 patients was performed utilizing our electronic medical record system (Epic Systems, Verona WI). Revenue was projected utilizing standard Medicare rates for our region while societal benefit was calculated using quality adjusted life years (QALY). Results: Of the 2251 patient charts reviewed, 791 patients (35.1%) were seen by Montefiore ophthalmologists within a year of the original screening date. Estimated revenue generated by these visits was $276,800, with the majority from the treatment of retinal disease ($208,535), and the remainder from other ophthalmic conditions detected in the fundus photos ($68,265). There was a societal benefit of 14.66 quality adjusted life years (QALYs) with an estimated value of $35,471/QALY. Conclusion: This telemedicine initiative was successful in identifying many patients with diabetic retinopathy and other ophthalmic conditions who may otherwise not have been formally evaluated. Our analysis demonstrates the program to generate a downstream revenue of nearly $280K with a cost benefit below <50% of the threshold of $100,000/QALY, and therefore cost-effective in marginalized communities.

Moxifloxacin releasing intraocular implant based on a cross-linked hyaluronic acid membrane.

Intraocular antibiotic delivery is an important technique to prevent bacterial infection after ophthalmic surgery, such as cataract surgery. Conventional drug delivery methods, such as antibiotic eye drops, have limitations for intraocular drug delivery due to the intrinsic barrier effect of the cornea. Therefore, frequent instillation of antibiotic eyedrops is necessary to reach a sufficient bactericidal concentration inside the eye. In this study, an intraocular implant, MXF-HA, that combines hyaluronic acid (HA) and moxifloxacin (MXF) was developed to increase the efficiency of intraocular drug delivery after surgery. MXF-HA is manufactured as a thin, transparent, yellow-tinted membrane. When inserted into the eye in a dry state, MXF-HA is naturally hydrated and settles in the eye, and the MXF contained therein is delivered by hydrolysis of the polymer over time. It was confirmed through in vivo experiments that MXF delivery was maintained in the anterior chamber of the eye at a concentration sufficient to inhibit Pseudomonas aeruginosa and Staphylococcus aureus for more than 5 days after implantation. These results suggest that MXF-HA can be utilized as a potential drug delivery method for the prevention and treatment of bacterial infections after ophthalmic surgery.

Transepithelial Corneal Crosslinking Using a Novel Ultraviolet Light-Emitting Contact Lens Device: A Pilot Study.

Purpose: To evaluate the feasibility of a novel, on-eye UVA light-emitting contact lens device driven by fiber optics for the corneal crosslinking (CXL) of patients with keratoconus. Methods: In nine corneal transplant candidates with advanced keratoconus a scleral contact lens reservoir containing 0.007% benzalkonium chloride preserved with 0.25% riboflavin-monophosphate was placed on the eye for 30 minutes. The reservoir lens was removed and replaced with the CXLens UVA light-emitting contact lens. A 375-nm UVA light at 4 mW/cm2 intensity was delivered for 30 minutes for a dose of 7.2 J/cm2. A one-sided paired t-test was used to evaluate mean differences in maximum keratometry, thinnest corneal thickness, and endothelial cell density between screening and 6 months after CXL. A two-sided paired t-test was used to evaluate differences in best-corrected distance visual acuity between screening and 6 months after CXL. Results: All patients received the treatment as per protocol and adhered to follow-up testing. At 6 months after CXL, treated eyes had an average -1.0 ± 1.6 diopters decrease in the maximum keratometry (P = 0.049), a nonsignificant 2.3 ± 7.5 letter improvement in best-corrected distance visual acuity (P = 0.19), a nonsignificant -17 ± 14 µm decrease in thinnest corneal thickness (P < 0.01), and a nonsignificant -86 ± 266 cells/mm2 decrease in endothelial cell density (P = 0.20). Conclusions: Our pilot study demonstrated the feasibility of the novel CXL device for the treatment of keratoconus and indicates the device is ready for larger scale studies with longer follow-up periods. Translational Relevance: The novel CXLens on-eye UVA light-emitting contact lens device offers the potential for efficient, high-throughput transepithelial corneal CXL.

Corneal Crosslinking in Refractive Corrections.

Translational Relevance: The clinical application of corneal crosslinking relies on a good understanding of the biomechanical effect of various treatment parameters on corneal tissue. We discuss the results of the clinical and laboratory studies evaluating corneal crosslinking as a primary refractive treatment.

Collagen Structural Changes in Rat Tarsus After Crosslinking.

Purpose: Surgery is the standard treatment for floppy eyelid syndrome, but crosslinking (CXL) tarsus has recently been proposed as an alternative. To the best of our knowledge, this study is the first to use second-harmonic generation (SHG) microscopy to examine tarsal collagen ex vivo before and after photo-activated crosslinking. To quantify crosslinking, this study examined fluorescence recovery after photobleaching (FRAP), which indirectly measures tissue stiffness. Methods: Upper eyelid tarsal plates were dissected from 21 Sprague-Dawley rats (total of 42 tarsal plates). Six normal plates were sent for histopathology and SHG imaging; the remaining 36 were crosslinked with phosphate-buffered saline (PBS) alone or riboflavin in PBS (concentrations of 0.1%, 0.3%, and 0.5%). Tissues were irradiated with 365-nm ultraviolet A light (power, 0.45 mW/cm2) for 30 minutes and immediately underwent SHG microscopy. Stiffness was indirectly measured with FRAP using fluorescein isothiocyanate (FITC)-dextran. Results: SHG imaging of normal tarsus showed that the organization of collagen bundles is complex and varies greatly depending on location. After crosslinking with high-concentration riboflavin (0.5%), collagen fibers showed clear structural changes, becoming more densely packed and wavier compared to control. FRAP half-time to fluorescence recovery was significantly increased (P < 0.05), indirectly indicating increased tissue stiffness. No structural changes were observed after crosslinking with lower riboflavin concentrations of 0.1% and 0.3%. Conclusions: This is the first report of SHG microscopy used to image tarsus collagen before and after crosslinking. These results highlight collagen structural changes, with effects on tissue stiffness indirectly confirmed by FRAP. Translational Relevance: Collagen fibers in the tarsus may be a therapeutic target for crosslinking in order to treat symptomatic floppy eyelid syndrome.

Evaluation of moxifloxacin-induced cytotoxicity on human corneal endothelial cells.

Moxifloxacin hydrochloride (MXF) is widely used for the prevention of bacterial endophthalmitis after intraocular surgeries. However, the safety issue of intracameral injection of MXF for human corneal endothelial cells (HCECs) is still debatable. In this study, we investigated concentration-dependent cytotoxicity (0.05-1 mg/ml) of MXF for immortalized HCECs (B4G12 cell) and the underlying mechanism. Reactive oxygen generation (ROS) and cell viability after MXF exposure was measured. Flow cytometric analysis and TUNEL assay was used to detect apoptotic HCECs after MXF exposure. Ultrastructure of damaged HCECs by MXF was imaged by transmission electron microscope. Western blot analysis and caspase 2, 3 and 8 analysis were used to reveal the underlying mechanism of MXF induced damage in HCECs. We found that MXF induced dose-dependent cytotoxicity in HCECs. MXF exposure increased ROS generation and induced autophagy in HCECs. Increased LDH release represented the cellular membrane damage by MXF. In addition, caspases activation, Bax/Bcl-xL-dependent apoptosis pathway and apoptosis inducing factor nuclear translocation were all involved in MXF induced HCECs' damage, especially after exposure to high dose of MXF (0.5 and 1.0 mg/ml). These findings suggest that MXF toxicity on HCECs should be thoroughly considered by ophthalmologists when intracameral injection of MXF is planned.

Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases.

Ocular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.

A Novel Therapeutic Approach to Corneal Alkaline Burn Model by Targeting Fidgetin-Like 2, a Microtubule Regulator.

Purpose: The purpose of this study was to determine the efficacy of nanoparticle-encapsulated Fidgetin-like 2 (FL2) siRNA (FL2-NPsi), a novel therapeutic agent targeting the FL2 gene, for the treatment of corneal alkaline chemical injury. Methods: Eighty 12-week-old, male Sprague-Dawley rats were divided evenly into 8 treatment groups: prednisolone, empty nanoparticles, control-NPsi (1 µM, 10 µM, and 20 µM) and FL2-NPsi (1 µM, 10 µM, and 20 µM). An alkaline burn was induced onto the cornea of each rat, which was then treated for 14 days according to group assignment. Clinical, histopathologic, and immunohistochemical analyses were conducted to assess for wound healing. FL2-NPsi-mediated knockdown of FL2 was confirmed by in vitro quantitative polymerase chain reaction (qPCR). Toxicity assays were performed to assess for apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling [TUNEL] assay) and nerve damage (whole mount immunochemical staining). Statistical analyses were performed using Student's t-test and ANOVA. Results: Compared with controls, FL2-NPsi-treated groups demonstrated enhanced corneal wound healing, with the 10 and 20 µM FL2-NPsi-treated groups demonstrating maximum rates of corneal re-epithelialization as assessed by ImageJ software, enhanced corneal transparency, and improved stromal organization on histology. Immunohistochemical analysis of vascular endothelial cells, macrophages, and neutrophils did not show significant differences between treatment groups. FL2-NPsi was not found to be toxic to nerves or induce apoptosis (p = 0.917). Conclusions: Dose-response studies found both 10 and 20 µM FL2-NPsi to be efficacious in this rat model. FL2-NPsi may offer a novel treatment for corneal alkaline chemical injuries. Translational Relevance: Basic cell biology findings about the microtubule cytoskeleton were used to design a therapeutic to enhance corneal cell migration, highlighting the promise of targeting microtubules to regulate corneal wound healing.

Penetrating ocular injury from motor vehicle rear-view side-mirror.

PURPOSE: To report a case of penetrating ocular injury due to automobile rear-view side-mirror. OBSERVATIONS: This is a case of a 49-year-old male who developed penetrating eye injury with a full thickness corneal laceration after isolated motor vehicle damage to the rear-view side-mirror. This patient subsequently required surgical repair of the corneal laceration and likely will need further surgical interventions in the future for ocular rehabilitation. CONCLUSIONS AND IMPORTANCE: Our case of rear-view side mirror caused injury and those previously reported highlight an area of opportunity for injury prevention.

Changes in Collagen Structure and Permeability of Rat and Human Sclera After Crosslinking.

Purpose: To use second harmonic generation imaging and fluorescence recovery after photobleaching to demonstrate alterations in scleral collagen structure and permeability after crosslinking in rat and human eyes. Methods: Excised rat and human scleras were imaged ex vivo with an inverted two-photon excitation fluorescence microscope before and after photochemical crosslinking using riboflavin and 405-nm laser light. Fluorescence recovery after photobleaching was applied to measure the diffusion of fluorescein isothiocyanate-dextran across the sclera. Results: Crosslinking caused scleral collagen fibers to become wavier and more densely packed, with surface collagen being more affected than deeper collagen fibers. Crosslinked sclera showed significantly decreased permeability in the irradiation zone and also extended as far as 250 µm outside the irradiation zone. Conclusions: Photochemical crosslinking induced changes in scleral structure and permeability that extended to tissue even outside the irradiation zone. Translational Relevance: Ultrastructural changes associated with the emerging clinical technique of photochemical scleral crosslinking have not been well characterized. We demonstrate not only changes in scleral collagen by second harmonic generation imaging but also the associated functional changes in tissue permeability by fluorescence recovery after photobleaching. We report the novel finding of reduced permeability extending well beyond the direct irradiation zone. This has implications for control in the clinical setting.

Preoperative, intraoperative, and postoperative assessment of corneal biomechanics in refractive surgery.

PURPOSE OF REVIEW: To review current and emerging methods and utilities of preoperative, intraoperative, and postoperative measurements of corneal biomechanics and their effects on refractive surgery decision-making. RECENT FINDINGS: Several recent clinical and preclinical studies have demonstrated the utility of corneal biomechanical analysis in refractive surgery. These studies focus on both screening surgical candidates for keratoconic disease as well as intraoperative and postoperative monitoring. The measurement of spatially resolved biomechanics is beginning to be studied in humans. SUMMARY: Clinically available screening methods combining corneal biomechanics with topographic and tomographic data provide increased utility when screening for keratoconic disorder. Spatially resolved measurement of corneal biomechanics holds great potential for preoperative, intraoperative, and postoperative evaluation of refractive surgery candidates as well as for more individualized procedures in the future.

Risk factors for postlaser refractive surgery corneal ectasia.

PURPOSE OF REVIEW: To summarize newly reported and update previously known risk factors for post laser vision correction (LVC) corneal ectasia. RECENT FINDINGS: Advances in corneal topography and tomography have improved detection of preclinical ectasia-related changes. This has allowed for enhanced screening of surgical candidates. There are also known genetic predispositions for corneal ectasia, and recent genetic analyses have revealed various genes and inflammatory biomolecular markers related to corneal biomechanical integrity. Other models of risk assessment such as finite element biomechanical modeling and artificial intelligence tools have shown promise in detecting more subtle risk factors, such as those related to mechanical strain. SUMMARY: Risk factors for post-LVC corneal ectasia involve both surgery and patient-specific characteristics, such as topographic and tomographic abnormalities, younger age, thinner preoperative corneas, and residual stromal beds, high myopia, and higher percentage tissue altered. Preoperative risk stratification has helped to decrease the incidence of postoperative ectasia, a trend which will likely continue with advancements in analytic tools and better understanding of underlying genetic predispositions.