Faculty Bibliography

PURPOSE/UNASSIGNED:The purpose of this study was to assess the utility of artificial intelligence (AI) assisted analysis of anterior segment optical coherence tomography (AS-OCT) imaging of the device-cornea joint in predicting outcomes of an intrastromal synthetic cornea device in a rabbit model. METHODS/UNASSIGNED:Sixteen rabbits underwent intrastromal synthetic cornea implantation. Baseline anterior lamellar thickness was established using AS-OCT intraoperatively. Monthly postoperative clinical examinations and AS-OCT imaging were performed, focusing on the peri-optic zone. A convolutional neural network was trained using a subset of manually marked images to automatically detect anterior lamellar tissue. Images were aligned manually using reference coordinates. The tissue volume data were evaluated as both absolute volume and percentage change from baseline using AI. RESULTS/UNASSIGNED:Sixteen rabbits were observed for 6 (n = 8) and 12 (n = 8) months. Mild focal anterior lamella thinning without retraction was seen near tight sutures in 2 rabbits (2/8) in the 6-month cohort, whereas 2 rabbits (2/8) in the 12-month cohort showed mild focal retraction from the optic stem with thinning. AI-assisted AS-OCT image analyses detected tissue volume reduction up to 3 months before clinical examination, with a reliable threshold of 5% change in tissue volume. CONCLUSIONS/UNASSIGNED:AI-assisted AS-OCT can detect peri-prosthetic tissue loss and predicting postoperative complications following an intrastromal synthetic cornea implantation in a rabbit model. Further studies are warranted to explore its clinical utility in human patients. TRANSLATIONAL RELEVANCE/UNASSIGNED:AI-assisted monitoring of peri-optic corneal tissue volume may be a useful screening modality to detect subclinical thinning after artificial corneal implantation and inform clinical decision making.

PURPOSE/OBJECTIVE:To assess whether slit-scanning specular microscopy (CellChek C; Konan Medical) can repeatedly image the same corneal location using anatomic landmarks (posterior corneal rings and corneal undulations) and unique cells identified during imaging. METHODS:A total of 203 eyes (113 patients) with and without corneal pathology were imaged to assess the prevalence of anatomic landmarks. A subcohort of 20 healthy eyes was used to identify unique cells adjacent to anatomic landmarks. Landmarks were then used to locate the same cells on repeat imaging approximately 1 week later. Endothelial cell density (ECD), coefficient of variation, and percent hexagonality were calculated. Intraclass correlation coefficient and 95% limits of agreement were used to measure variability and reproducibility of imaging. RESULTS:Approximately 91% of eyes had either posterior corneal rings or undulations present. Undulations were more common than posterior corneal rings in both healthy and diseased corneas. Among subcohort eyes, unique cells were found adjacent to anatomic landmarks in 100% of eyes. Landmarks were used to reimage the same cells in 75% of eyes. There was minimal variation in ECD, coefficient of variation, and hexagonality; intraclass correlation coefficient and 95% confidence intervals were 0.891 [0.715-0.962], 0.612 [0.179-0.849], and 0.793 [0.499-0.925], respectively. The 95% limits of agreement for ECD was -359.9-260.98. CONCLUSIONS:Landmarks identified with slit-scanning specular microscopy allowed reliable reimaging of the same endothelial location, providing a powerful tool to better understand the role of the peripheral endothelium in health and disease.

Targeted cancer therapies have transformed the landscape of cancer treatments but are often associated with off-target adverse drug reactions due to overlapping molecular pathways in healthy tissues, including those in the eye. Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. AEs across clinical trials are graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), which may not completely capture the ocular sequelae resulting from the use of emerging therapies. As CTCAE grading is mainly through the description of symptoms and their impact on visual acuity, it is imperative to use a tool that relies more on objective findings from ophthalmologic evaluations. The novel ocular adverse reaction severity grading scale developed by Amgen in collaboration with expert ophthalmologists, accounts for the anatomical regions impacted by ocular adverse reactions and anchors each severity grade to objective observable criteria from ophthalmologic evaluations. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care.

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.