The Resistance of Riboflavin/UV-A Corneal Cross-Linking to Enzymatic Digestion Is Oxygen-Independent.

PURPOSE: Corneal cross-linking (CXL) with riboflavin and UV-A induces several effects in the cornea, including biomechanical stiffening, generation of reactive oxygen species, and increased resistance to enzymatic digestion. Whereas the biomechanical stiffening effect is oxygen-dependent, little is known about the effect of oxygen on the resistance to enzymatic digestion. Here, we examined CXL-induced enzymatic resistance in the absence of oxygen. METHODS: Ex vivo porcine corneas (n = 160) were assigned to 5 groups. Group 1 was the control group (abrasion and riboflavin application). Groups 2 and 3 received accelerated 10 and 15 J/cm2 high-fluence CXL protocols in the presence of oxygen (9'15″ @ 18 mW/cm2 and 8'20″ @ 30 mW/cm2, respectively), whereas groups 4 and 5 received accelerated 10 and 15 J/cm2 high-fluence CXL protocols in the absence of oxygen (oxygen content less than 0.1%). After CXL, corneas were digested in 0.3% collagenase A solution. Mean time until complete dissolution was determined. RESULTS: The mean times to digestion in groups 1 through 5 were 22.31 ± 1.97 hours, 30.78 ± 1.83 hours, 32.22 ± 2.22 hours, 31.38 ± 2.18 hours, and 31.69 ± 2.53 hours, respectively. Experimental CXL groups showed significantly higher (P < 0.001) resistance to digestion than nonirradiated controls. There was no significant difference in time to digestion across all experimental CXL groups, irrespective of fluence delivered or the absence of oxygen. CONCLUSIONS: The resistance to digestion in accelerated high-fluence riboflavin/UV-A CXL is oxygen-independent, which is of particular importance when developing future optimized CXL protocols for corneal ectasia and infectious keratitis.

Combining Riboflavin/UV-A Light and Rose Bengal/Green Light Corneal Cross-Linking Increases the Resistance of Corneal Enzymatic Digestion.

Purpose: The purpose of this study was to determine if concurrent riboflavin/UV-A light (RF/UV-A) and rose Bengal/green light (RB/green) epi-off PACK-CXL enhances corneal resistance to enzymatic digestion compared to separate chromophore/light treatments. Methods: Ex vivo porcine corneas were allocated as follows. Group A corneas were soaked with riboflavin (RF) and were either not irradiated (A1, controls) or were irradiated with 10 (A2) or 15 J/cm² (A3) UV-A light at 365 nm, respectively. Group B corneas were soaked with RB and either not irradiated (B1, controls) or were illuminated with 10 (B2) or 15 J/cm² (B3) green light at 525 nm, respectively. Corneas in group C were soaked with both RF and RB and were either not irradiated (C1, controls) or were subjected to the same session consecutive 10 J/cm2 (C2) or 15 J/cm2 (C3) UV-A and green light exposure. Following treatment, all corneas were exposed to 0.3% collagenase A to assess digestion time until corneal button dissolution. Results: A1 to A3 digestion times were 21.38, 30.5, and 32.25 hours, respectively, with A2 and A3 showing increased resistance to A1. B1-3 had digestion times of 31.2, 33.81, and 34.38 hours, with B3 resisting more than B1. C1 to C3 times were 33.47, 39.81, and 51.94 hours; C3 exhibited superior resistance to C1 and C2 (both P < 0.05). Conclusions: Same-session combined RF/UV-A and RB/green PACK-cross-linking significantly increases corneal enzymatic digestion resistance over standalone treatments. Translational Relevance: Combining RF-based and RB-based PACK-CXL considerably increases corneal collagenase digestion resistance, potentially minimizing ulcer size in clinical contexts.

Effect of accelerated high-fluence riboflavin and rose bengal-mediated corneal cross-linking on resistance to enzymatic digestion.

PURPOSE: This study evaluated the effect of high-fluence accelerated corneal cross-linking on the resistance to enzymatic digestion, assessing two chromophore/light combinations: riboflavin/UV-A light (RF/UV-A) and rose bengal/green light (RB/green). METHODS: Freshly prepared ex-vivo porcine corneas (n = 189) were divided into 8 groups groups. Group A corneas were unirradiated controls without chromophore soaking (A0), or soaked with riboflavin (A1) or rose bengal (A2). Group B corneas underwent accelerated epi-off RF/UV-A CXL at fluences of 5.4 J/cm² (B1), 10 J/cm² (B2), or 15 J/cm² (B3). Group C corneas underwent accelerated epi-off RB/green CXL at fluences of either 10 J/cm² (C1) or 15 J/cm² (C2). Following CXL, all corneas were digested in 0.3% collagenase-A solution, and the time until complete dissolution was measured. RESULTS: Non-irradiated controls exposed to RF and RB enhanced corneal resistance to collagenase digestion, with RB having a stronger effect than RF. RF/UV-A-treated corneas showed significantly increased digestion resistance with increasing fluence levels. RB/green-treated corneas displayed enhanced digestion resistance with each increase in fluence up to 10 J/cm²; a 15 J/cm² fluence yielded similar digestion resistance times to a 10 J/cm² fluence, suggesting a plateau effect in accelerated RB/green CXL protocols. CONCLUSIONS: When compared to standard-fluence treatments, high-fluence accelerated epi-off CXL using both riboflavin and rose bengal significantly increases resistance to enzymatic digestion. The optimal settings for clinical protocols might be 15 J/cm² (30 mW/cm² for 8 min 20 s) for RF/UV-A and 10 J/cm² (15 mW/cm² for 11 min 7 s) for RB/Green Light.

High-Fluence Accelerated PACK-CXL for Bacterial Keratitis Using Riboflavin/UV-A or Rose Bengal/Green in the Ex Vivo Porcine Cornea.

Purpose: To investigate and compare the efficacy of high-fluence accelerated photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) using either riboflavin/ultraviolet (UV)-A light or rose bengal/green light to treat Staphylococcus aureus or Pseudomonas aeruginosa infections in an ex vivo porcine cornea model. Methods: One hundred and seventeen ex vivo porcine corneas were injected with clinical isolates of S. aureus or P. aeruginosa, divided into eight groups, and cultured for 24 hours. Then, either riboflavin with UV-A light irradiation (30 mW/cm2; 8 minutes, 20 seconds; 15 J/cm2) or rose bengal with green light irradiation (15 mW/cm2, 16 minutes, 40 seconds; 15 J/cm2) was applied; unirradiated infected groups served as controls. All corneas were incubated for another 24 hours. Next, corneal buttons were obtained and vortexed to release the bacterial cells. The irradiated and unirradiated solutions were then plated and incubated on agar plates. The amount of colony-forming units was quantified and the bacterial killing ratios (BKRs) resulting from different PACK-CXL protocols relative to non-treated controls were calculated. Results: Riboflavin/UV-A light PACK-CXL resulted in median BKRs of 52.8% and 45.8% in S. aureus and P. aeruginosa, respectively, whereas rose bengal/green light PACK-CXL resulted in significantly greater BKRs of 76.7% and 81.0%, respectively (both P < 0.01). Conclusions: Both accelerated PACK-CXL protocols significantly decreased S. aureus and P. aeruginosa bacterial loads. Comparing the riboflavin/UV-A light and rose bengal/green light PACK-CXL approaches in the same experimental setup may help develop strain-specific and depth-dependent PACK-CXL approaches that could be used alongside the current standard of care. Translational Relevance: Our study used an animal model to gain insight into the efficacy of high-fluence accelerated PACK-CXL using either riboflavin/UV-A light or rose bengal/green light to treat Staphylococcus aureus or Pseudomonas aeruginosa infections.

Accelerated high fluence photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study.

Introduction: Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) has garnered substantial interest among researchers and ophthalmologists due to its high promise as a potential treatment for infectious keratitis. The aim of this study is to evaluate the efficacy and safety of high fluence PACK-CXL, using 10.0 J/cm2 (30 mW/cm2, 5 min, and 33 s) at the slit lamp. Methods: This prospective interventional, nonrandomized cohort study included 20 eyes of 20 patients with bacterial, fungal, or mixed origin keratitis who underwent high fluence PACK-CXL treatment as an adjunct therapy to conventional antimicrobial therapy per American Academy of Ophthalmology treatment guidelines. The re-epithelization time was recorded, and corneal endothelial cell density was counted before and after treatment. Results: The average re-epithelization time was 8.2 ± 2.8 days (range 3-14 days). After PACK-CXL treatment, eight patients (40%) were directly discharged, while the remained patients stayed in the hospital for an average of 5.6 ± 3.5 days. No eyes required keratoplasty. Endothelial cell density counts before and after the PACK-CXL procedure were 2,562.1 ± 397.3, and 2,564.8 ± 404.5 cells/mm2, respectively (p = 0.96). Conclusion: although it was not a randomized control trial, we conclude that high fluence PACK-CXL as an adjuvant therapy is safe with no complications observed, and efficient as time to re-epithelization was less than 14 days for all patients and no patients underwent tectonic keratoplasties. Further research is needed to compare it to the current standard of care.

New keratoconus staging system based on OCT.

PURPOSE: To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. SETTING: Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGNS: Retrospective case-control study. METHODS: Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems. RESULTS: 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90%, specificity 67%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75%, specificity 78%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed. CONCLUSIONS: The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management.

Rates of infectious keratitis and other ocular surface adverse events in corneal cross-linking for keratoconus and corneal ectasias performed in an office-based setting: a retrospective cohort study.

BACKGROUND: This study aimed to compare the complication rates of epithelium-off corneal cross-linking (epi-off CXL) performed in an office-based setting with those of epi-off CXL performed in an operating room. METHODS: A retrospective cohort study, comprising 501 consecutive epi-off CXL procedures, performed in a non-sterile procedure room without laminar flow ventilation at the ELZA Institute in Zurich, Switzerland, between November 2015 and October 2021, was conducted. RESULTS: No cases of postoperative infectious keratitis were observed, while sterile infiltrates occurred in 10 out of 501 (2.00%) patients, all of whom responded well to topical steroid therapy. Delayed epithelialization (> 7 days) occurred in 14 out of 501 (2.79%) patients. No other adverse events were noted. CONCLUSIONS: Office-based epi-off CXL does not appear to be associated with an increased risk of complications when compared to operating room settings.

Corneal crosslinking with riboflavin using sunlight.

PURPOSE: To assess whether sunlight might be used to induce a biomechanical stiffening effect in riboflavin-soaked corneas similar to the effect observed in corneal crosslinking (CXL) using riboflavin and UV-A light. SETTING: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland. DESIGN: Experimental study. METHODS: 52 porcine eyes were assayed. The concentration of riboflavin in the corneal stroma was estimated using UV-A transmission in a preliminary experiment. Then, the duration of sunlight exposure to achieve a fluence of 7.2/cm 2 was calculated. Finally, de-epithelialized corneas were divided equally into 3 groups and soaked with riboflavin 0.1% (control group and Group 1) or 0.5% (Group 2). Eyes from Groups 1 and 2 were then exposed to sunlight. The elastic modulus was calculated as an indicator of stiffness. RESULTS: Riboflavin concentration in Group B was higher by a factor of 2.8 than Group A. According to live illuminance measurements and stromal riboflavin concentration, the sunlight exposure duration varied between 16 minutes and 45 minutes. Groups 1 and 2 had higher elastic modulus than controls ( P < .0001) but did not differ between them ( P = .194). The stiffening effect was 84% and 55%, respectively. CONCLUSIONS: Sunlight exposure of ex vivo corneas soaked in both riboflavin 0.1% and 0.5% resulted in increased corneal stiffness. Specifically, riboflavin 0.1% with longer UV-A exposure showed a trend for a greater stiffening effect, which might open new alleys for the use of oral riboflavin and fractioned sunlight exposure as less invasive CXL techniques.

Combinations of Scheimpflug tomography, ocular coherence tomography and air-puff tonometry improve the detection of keratoconus.

PURPOSE: To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC). METHODS: Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity. RESULTS: 271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy. CONCLUSION: Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest.

The Antibacterial Efficacy of High-Fluence PACK Cross-Linking Can Be Accelerated.

Purpose: To determine whether high-fluence photoactivated chromophore for keratitis cross-linking (PACK-CXL) can be accelerated. Methods: Solutions of Staphylococcus aureus and Pseudomonas aeruginosa with 0.1% riboflavin were prepared and exposed to 365 nm ultraviolet (UV)-A irradiation of intensities and fluences from 9 to 30 mW/cm2 and from 5.4 to 15.0 J/cm2, respectively, representing nine different accelerated PACK-CXL protocols. Irradiated solutions and unirradiated controls were diluted, plated, and inoculated on agar plates so that the bacterial killing ratios (BKR) could be calculated. Additionally, strains of Achromobacter xylosoxidans, Staphylococcus epidermidis, and Stenotrophomonas maltophilia were exposed to a single accelerated PACK-CXL protocol (intensity: 30 mW/cm2, total fluence: 15.0 J/cm2). Results: With total fluences of 5.4, 10.0, and 15.0 J/cm2, the range of mean BKR for S. aureus was 45.78% to 50.91%, 84.13% to 88.16%, and 97.50% to 99.90%, respectively; the mean BKR for P. aeruginosa was 69.09% to 70.86%, 75.37% to 77.93%, and 82.27% to 91.44%, respectively. The mean BKR was 41.97% for A. xylosoxidans, 65.38% for S. epidermidis, and 78.04% for S. maltophilia for the accelerated PACK-CXL protocol (30 mW/cm2, 15 J/cm2). Conclusions: The BKR of high-fluence PACK-CXL protocols can be accelerated while maintaining a high, but species-dependent, BKR. The Bunsen to Roscoe law is respected in fluences up to 10 J/cm2 in S. aureus and P. aeruginosa, whereas fluences above 10 J/cm2 show strain dependence. Translational Relevance: The high-fluence PACK-CXL protocols can be accelerated in clinical practice while maintaining high levels of BKR.

Effect of fluence levels on prophylactic corneal cross-linking for laser in situ keratomileusis and transepithelial photorefractive keratectomy.

PURPOSE: The purpose of this study is to assess the effect of various fluence levels on prophylactic corneal cross-linking (CXL) combined with femtosecond laser in situ keratomileusis (FS-LASIK-Xtra) or transepithelial photorefractive keratectomy (TransPRK-Xtra) on biomechanics, demarcation line (DL), and stromal haze. METHODS: Prospective analysis where two prophylactic CXL protocols (lower/higher fluence [LF/HF]: 30 mw/cm2 , 60/80 s, 1.8/2.4 J/cm2 ) were performed as part of either an FS-LASIK-Xtra or TransPRK-Xtra procedure. Data were collected preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Main outcome measures were (1) dynamic corneal response parameters and the stress-strain index (SSI) from Corvis, (2) actual DL depth (ADL), and (3) stromal haze on OCT images analysed by a machine learning algorithm. RESULTS: Eighty-six eyes from 86 patients underwent FS-LASIK-Xtra-HF (21 eyes), FS-LASIK-Xtra-LF (21 eyes), TransPRK-Xtra-HF (23 eyes), and TransPRK-Xtra-LF (21 eyes). SSI increased similarly by around 15% in all groups 6 months postoperatively (p = 0.155). All other corneal biomechanical parameters were statistically significant worsening postoperatively, but the change was similar in all groups. At 1 month postoperatively, there was no statistical difference in mean ADL among four groups (p = 0.613), mean stromal haze was similar between the two FS-LASIK-Xtra groups, but higher in the TransPRK-Xtra-HF group compared with the TransPRK-Xtra-LF group. CONCLUSIONS: FS-LASIK-Xtra and TransPRK-Xtra lead to a similar ADL and improve SSI equally. Lower fluence prophylactic CXL might be recommended as it achieves similar mean ADL with potentially less induced stromal haze, especially in TransPRK. The clinical relevance and applicability of such protocols remains to be assessed.

Progressive keratoconus in patients older than 48 years.

PURPOSE: To report cases of progressive keratoconus (KC) in patients aged ≥48 years and the successful arrest of progression using corneal cross-linking (CXL) with riboflavin and ultraviolet-A light. OBSERVATIONS: Five eyes from four patients with progressive KC aged 48, 48, 51 and 54 years are reported in this case series. All eyes were followed regularly after initial diagnosis. Kmax was used as an indicator of progression and KC progressed at a rate of 1.4 diopters in 6 months and 14.6 diopters in 14 months. All patients eventually received CXL, and all were aged ≥50 years at the time of the procedure. One eye required two CXL procedures to successfully stabilize the patient's cornea. CONCLUSION: Despite the probability of KC progression strongly declining after the age of 40 years, it never becomes zero. It is therefore advisable to continue regular follow-up corneal tomography examinations in patients with KC, even in their fifth and sixth decades of life.

Optimized Artificial Intelligence for Enhanced Ectasia Detection Using Scheimpflug-Based Corneal Tomography and Biomechanical Data.

PURPOSE: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection. DESIGN: 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.

Demarcation Line Depth in Epithelium-Off Corneal Cross-Linking Performed at the Slit Lamp.

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.

Repeated application of riboflavin during corneal cross-linking does not improve the biomechanical stiffening effect ex vivo.

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: Sixty-six porcine corneas with intact epithelium were divided into three groups and analyzed. All corneas were pre-soaked with an iso-osmolar solution of 0.1% riboflavin in a phosphate-buffered saline (PBS) solution ("riboflavin solution"). Then, the corneas in Groups 1 and 2 were irradiated with a standard epi-off CXL (S-CXL) UV-A irradiation protocol (3 mW/cm2 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.

Combining Spectral-Domain OCT and Air-Puff Tonometry Analysis to Diagnose Keratoconus.

PURPOSE: To investigate the diagnostic capacity of spectral-domain optical coherence tomography (SD-OCT) combined with air-puff tonometry using artificial intelligence (AI) in differentiating between normal and keratoconic eyes. METHODS: Patients who had either undergone uneventful laser vision correction with at least 3 years of stable follow-up or those who had forme fruste keratoconus (FFKC), early keratoconus (EKC), or advanced keratoconus (AKC) were included. SD-OCT and biomechanical information from air-puff tonometry was divided into training and validation sets. AI models based on random forest or neural networks were trained to distinguish eyes with FFKC from normal eyes. Model accuracy was independently tested in eyes with FFKC and normal eyes. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity values. RESULTS: A total of 223 normal eyes from 223 patients, 69 FFKC eyes from 69 patients, 72 EKC eyes from 72 patients, and 258 AKC eyes from 258 patients were included. The top AUC ROC values (normal eyes compared with AKC and EKC) were Pentacam Random Forest Index (AUC = 0.985 and 0.958), Tomographic and Biomechanical Index (AUC = 0.983 and 0.925), and Belin-Ambrósio Enhanced Ectasia Total Deviation Index (AUC = 0.981 and 0.922). When SD-OCT and air-puff tonometry data were combined, the random forest AI model provided the highest accuracy with 99% AUC for FFKC (75% sensitivity; 94.74% specificity). CONCLUSIONS: Currently, AI parameters accurately diagnose AKC and EKC, but have a limited ability to diagnose FFKC. AI-assisted diagnostic technology that uses both SD-OCT and air-puff tonometry may overcome this limitation, leading to improved treatment of patients with keratoconus. [J Refract Surg. 2022;38(6):374-380.].

Repeatability of a Scheimpflug tonometer to measure biomechanical parameters before and after myopic refractive surgery.

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.

Detection of postlaser vision correction ectasia with a new combined biomechanical index.

PURPOSE: To validate and evaluate the use of a new biomechanical index known as the Corvis biomechanical index-laser vision correction (CBI-LVC) as a method for separating stable post-LVC eyes from post-LVC eyes with ectasia. SETTING: 10 clinics from 9 countries. DESIGN: Retrospective, multicenter, clinical study. METHODS: The study was designed with 2 purposes: to develop the CBI-LVC, which combines dynamic corneal response (DCR) parameters provided by a high-speed dynamic Scheimpflug camera (CorVis ST; OCULUS Optikgeräte GmbH) and then to evaluate its ability to detect post-LVC ectasia. The CBI-LVC includes integrated inverse radius, applanation 1 (A1) velocity, A1 deflection amplitude, highest concavity and arclength, deformation amplitude ratio of 2 mm, and A1 arclength in millimeters. Logistic regression with Wald forward stepwise approach was used to identify the optimal combination of DCRs to create the CBI-LVC and then separate stable from LVC-induced ectasia. Eighty percentage of the database was used for training the software and 20% for validation. RESULTS: 736 eyes of 736 patients were included (685 stable LVC and 51 post-LVC ectasia). The receiver operating characteristic curve analysis showed an area under the curve of 0.991 when applying CBI-LVC in the validation dataset and 0.998 in the training dataset. A cutoff of 0.2 was able to separate stable LVC from ectasia with a sensitivity of 93.3% and a specificity of 97.8%. CONCLUSIONS: The CBI-LVC was highly sensitive and specific in distinguishing stable from ectatic post-LVC eyes. Using CBI-LVC in routine practice, along with topography and tomography, can aid the early diagnosis of post-LVC ectasia and allow intervention prior to visually compromising progression.

Effect of intraoperative mitomycin-C application on epithelial regeneration after transepithelial photorefractive keratectomy.

PURPOSE: To investigate the effect of mitomycin-C (MMC) intraoperative application on postoperative corneal epithelial remodeling, haze incidence, and refractive correction in transepithelial photorefractive keratectomy (transPRK). SETTING: Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGN: Prospective randomized controlled study. METHODS: Eyes that completed all follow-ups were included. Epithelial thickness (ET) map measurement was conducted preoperatively and at 1 week, and at 1 month, 3 months, and 6 months postoperatively, generating ET in central, paracentral, and midperipheral zones. The difference between postoperative and preoperative ET (ΔET) was computed for each zone. During follow-up, haze incidence and visual acuity were assessed and compared between groups. RESULTS: A total of 100 eyes completed all follow-up, including 40 eyes treated with MMC in MMC group and 60 eyes in control group without MMC treatment. For ΔET, between-group difference was found in midperipheral (P = .011) zone at 1 week postoperatively and in central (P = .036) and paracentral zones (P = .039) at 1 month postoperatively. Haze incidence was lower in MMC group at 1 week and 1 month postoperatively (P = .035 and .018, respectively). Safety index (postoperative uncorrected distance visual acuity/preoperative corrected distance visual acuity [CDVA]) and efficacy index (postoperative CDVA/preoperative CDVA) were higher in MMC group (P = .012 and P = .036, respectively) at 1 month postoperatively. No difference was found after 3 months postoperatively. CONCLUSIONS: With a temporary impact on corneal epithelial regeneration and refractive correction, intraoperative MMC application in transPRK decreased the haze incidence but had no effect on epithelial remodeling.