Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this study was to characterize the morphological and immunological aspects of biointegration at the optic-cornea joint of a second-generation synthetic corneal device. METHODS:The initial prototype, single-piece optic-skirt configuration, is constructed from compact and flexible perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene (ePTFE) overlying the skirt to allow skirt-cornea biointegration. The second-generation version was modified to add ePTFE around the optic wall to allow optic-cornea biointegration. Initial and amended second-generation devices were implanted into healthy rabbit eyes. Clinical examination, anterior segment optical coherence tomography, light microscopy, and immunofluorescence studies were performed to assess structural integrity and determine molecular signatures indicative of inflammation and tissue remodeling between the 2 prototypes. RESULTS:Recipient eyes with both device versions showed no epithelial defects or tissue retraction at 3 months postoperatively. Optical coherence tomography images demonstrated no appreciable perioptic space with either prototype. Histopathology of the initial device demonstrated lack of stromal adhesion at the optic-cornea joint with epithelium filling the perioptic space. Second-generation devices demonstrated full sealing of the recipient stroma along the optic stem. Although the routine histopathology did not demonstrate inflammatory cells in the recipient cornea with either device, immunohistochemistry stains demonstrated quiescent phenotype of stromal and epithelial cells only in the second-generation devices. CONCLUSIONS:Biointegration between the synthetic corneal device and recipient tissue at the optic-cornea joint seems to avert inflammation and may help prevent sterile tissue lysis and prolong retention.

PURPOSE/OBJECTIVE:The aim of this study was to describe variations in practice patterns for the management of zone 1 open globe injuries among corneal specialists worldwide. METHODS:This cross-sectional study was performed using an online survey distributed to members of The Cornea Society. Responses were collected between September 9, 2021, and September 30, 2021. RESULTS:Of 94 responses included in analysis, respondents averaged 18.2 ± 14.5 years of postfellowship experience. Among respondents, 53 (56.4%) were affiliated with an academic institution and 41 (43.6%) with private practice. Ophthalmologists practicing in the United States were significantly more likely to use an eye shield preoperatively (98.5% vs. 85.7%, P = 0.03) and less likely to perform primary lensectomy in cases of lens involvement (40.9% vs. 75.0%, P = 0.002) compared with those practicing outside the United States. Ophthalmologists in practice fewer than 10 years were more likely to administer preoperative systemic antibiotics (91.4% vs. 66.1%, P = 0.006) and tetanus prophylaxis (88.6% vs. 67.8%, P = 0.03), and to obtain preoperative computed tomography scans (85.7% vs. 54.2%, P = 0.002) compared with more senior physicians. Ophthalmologists at academic institutions were more likely to perform preoperative B-scan (30.2% vs. 9.8%, P = 0.02), use general anesthesia (90.6% vs. 70.7%, P = 0.03), and admit for postoperative antibiotics (28.3% vs. 9.8%, P = 0.04), and were less likely to perform surgery overnight (45.3% vs. 70.7%, P = 0.02) compared with private practice physicians. CONCLUSIONS:There is significant variation in the practice patterns for the management of zone 1 open globe injuries among corneal specialists, which presents an opportunity to investigate whether certain treatment options lead to better outcomes in these injuries.

PURPOSE/UNASSIGNED:We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. METHODS/UNASSIGNED:Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. RESULTS/UNASSIGNED:The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. CONCLUSIONS/UNASSIGNED:The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. TRANSLATIONAL RELEVANCE/UNASSIGNED:We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

PURPOSE:To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. METHODS:Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. RESULTS:There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. CONCLUSIONS:Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. TRANSLATIONAL RELEVANCE:Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

PURPOSE/OBJECTIVE:The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS). METHODS:ZEDS is a National Eye Institute-supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status. RESULTS:Over approximately 4 years, over 400 study participants have been enrolled. CONCLUSIONS:ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.

ABSTRACT/UNASSIGNED:Descemet stripping only (DSO) has become a viable treatment option for certain cases of Fuchs Endothelial Corneal Dystrophy (FECD). This article describes the history of the development of DSO, its current status, and what successful DSO tells us about the pathophysiology of FECD. Remaining questions and future directions are also highlighted.