Faculty Bibliography

PURPOSE/OBJECTIVE:To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection. DESIGN/METHODS:Multicenter cross-sectional case-control retrospective study. METHODS:A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy. RESULTS:The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001). CONCLUSIONS:AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

PURPOSE:To evaluate whether repeated application of riboflavin during corneal cross-linking (CXL) has an impact on the corneal biomechanical strength in ex-vivo porcine corneas. DESIGN:Laboratory investigation. METHODS:for 30 min); while the corneas in Group 3 were not irradiated and served as control. During irradiation, Group 1 (CXL-PBS-Ribo) received repeated riboflavin solution application while corneas in Group 2 (CXL-PBS) received only repeated iso-osmolar PBS solution. Immediately after the procedure, 5-mm wide corneal strips were prepared, and elastic modulus was calculated to characterize biomechanical properties. RESULTS:Significant differences in stress-strain extensiometry were found between two cross-linked groups with control group (P = 0.005 and 0.002, respectively). No significant difference was observed in the normalized stiffening effect between Groups 1 and 2 (P = 0.715). CONCLUSIONS:The repeated application of riboflavin solution during UV-A irradiation does not affect the corneal biomechanical properties achieved with standard epi-off CXL. Riboflavin application during CXL may be omitted without altering the biomechanical stiffening induced by the procedure.

Infectious keratitis is a common and painful disease, usually caused by bacteria in dogs. Brachycephalic breeds are at increased risk. Despite medical therapy, enzymatic corneal melting can lead to ulcer perforation and globe loss. Treatment alternatives are needed due to an increase in antibiotic resistance and growing popularity of brachycephalic dogs. Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) reduces enzymatic collagenolysis and damages multiple targets within microorganisms, resulting in corneal tissue stabilization and elimination of bacteria, irrespective of their antibiotic resistance status. A randomized controlled trial providing evidence of PACK-CXL effectiveness in dogs is lacking. We aim to determine whether PACK-CXL is a viable alternative to conventional medical therapy for canine infectious keratitis. Two hundred-and-seventy client-owned dogs with presumed infectious keratitis will be allocated to two equally sized treatment groups (PACK-CXL or medical therapy) in a masked, randomized, controlled, multicenter trial in eleven clinics. The primary outcome measure is treatment success defined as complete epithelial closure within 28 days. The sample size is based on a group sequential design with two interim analyses, which will be overseen by a Data Safety and Monitoring Board. Ethical approvals have been obtained. The study protocol is preregistered at preclinicaltrials.eu. Publishing trial protocols improves study reproducibility and reduces publication bias.

We aimed to evaluate the depth of the demarcation line following accelerated epithelium-off corneal cross-linking (A-CXL) performed at the slit lamp with the patient sitting in an upright position. Twenty-three eyes from twenty patients, undergoing epi-off A-CXL (9 mW/cm² for 10 min) using a CXL device at the slit lamp in the upright position. Demarcation line depth was assessed at 1 month after the procedure using anterior segment optical coherence tomography (AS-OCT) and specialized software. Surgery was uneventful in all cases. The average postoperative demarcation line depth achieved was 189.4 µm (standard deviation: 58.67 µm). The demarcation line depth achieved with patients sitting upright, receiving CXL at the slit lamp, is similar to published data on CXL performed in the supine position, suggesting that demarcation line depth is not dependent on patient orientation during CXL.

When treating corneal ectasias, successful corneal cross-linking (CXL) requires three factors: riboflavin saturation of the corneal stroma, ultraviolet (UV) light, and oxygen. Riboflavin is too large to pass through epithelial tight junctions, so traditionally epithelial debridement is performed before riboflavin is applied making this approach an epithelium-off (epi-off) technique. However, this can result in pain as the epithelium regrows, corneal haze, and an increased infection risk postoperatively, which needs careful management with pharmacotherapy. Epithelium-on (epi-on) CXL should reduce the extent of these issues. Riboflavin can be passed through the epithelium into the stroma either by iontophoresis or with penetration enhancers, however this alone results in suboptimal cross-linking effects, as the epithelium not only absorbs around 20% of incoming UV energy, it also acts as a barrier to oxygen diffusion into the stroma. While it is simple to adjust the UV fluence delivered to the stroma to compensate for the energy lost in the epithelium, compensating for the lack of stromal oxygen is less simple. Several approaches (including oxygen goggles) have been taken to achieve this. However, adding iontophoresis and supplemental oxygen through goggles in the operating theater adds complexities that could be engineered out. Accordingly, the technique has advanced in the laboratory to a point where penetration enhancers, optimized UV irradiation profiles, and atmospheric oxygen can now provide epi-on CXL with the same corneal strengthening efficacy as epi-off CXL, suggesting simple, effective epi-on CXL could soon be in clinical use.

PURPOSE:To assess the repeatability of several corneal biomechanical parameters with a Scheimpflug tonometer (Corvis ST) in myopic eyes and eyes that underwent transepithelial photorefractive keratectomy (transPRK), small-incision lenticule extraction (SMILE), or femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. SETTING:Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGN:Prospective randomized controlled study. METHODS:315 eyes from 315 patients (135 myopes, 58 post-transPRK, 52 post-SMILE, and 70 post-FS-LASIK) were included. 3 consecutive scans were performed to evaluate the repeatability of the 40 parameters examined. RESULTS:315 eyes were included. In all eyes, the coefficient of variation (CoV) for intraocular pressure (IOP) and biomechanical-corrected IOP (bIOP) ranged from 7.29% to 9.47% and 6.11% to 7.75%, respectively; the CoV of pachymetry was <0.8%. The intraclass correlation coefficient of Corvis Biomechanical Index-Laser Vision Correction (LVC) was 0.680 for post-transPRK, 0.978 for post-SMILE, and 0.911 for post-FS-LASIK. The CoV of Stress-Strain Index (SSI) was 204.93% for post-transPRK, 91.92% for post-SMILE, and 171.72% for post-FS-LASIK. The CoV of the 6 clinically important dynamic corneal response parameters ranged from 2.0% to 7.8% for myopia, 1.8% to 11.1% for post-transPRK, 2.1% to 8.7% for post-SMILE, and 1.8% to 8.8% for post-FS-LASIK. CONCLUSIONS:Excellent intrameasurement repeatability of IOP, bIOP, and pachymetry was observed in all groups; SSI measurement in post-LVC corneas displayed more variation. Caution is warranted when assessing SSI in post-LVC corneas for the purpose of diagnosing iatrogenic ectasia or evaluating biomechanical remodeling of postoperative refractive corneas.