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.

Accelerated corneal crosslinking with 20'-soaking hydroxypropyl methyl cellulose/riboflavin vs conventional crosslinking with 30'-soaking dextran/riboflavin.

PURPOSE: To evaluate and compare functional and structural outcomes of accelerated corneal crosslinking (A-CXL) using riboflavin with hydroxypropyl methyl cellulose (HPMC) vs conventional corneal crosslinking (C-CXL) using riboflavin with dextran. SETTING: American University of Beirut Medical Center, Beirut, Lebanon. DESIGN: Retrospective analysis. METHODS: Retrospective analysis of 83 eyes of 73 patients with mild to moderate keratoconus. First group (n = 44 eyes) underwent C-CXL using a 30-minute riboflavin/dextran soaking between June 2014 and March 2016. Second group (n = 39 eyes) underwent A-CXL using a 20-minute riboflavin/HPMC soaking between April 2016 and December 2017. Patients were evaluated preoperatively and at 1, 3, and 12 months postoperatively. Main outcome measures were simulated keratometry (simK), maximum axial keratometry (Kmax), demarcation line depth, and haze intensity measured using optical coherence tomography-based image analysis software. RESULTS: Demarcation line (DL) was 298.30 ± 64.60 µm and 335.61 ± 99.76 µm for C-CXL and A-CXL groups, respectively ( P = .04). Haze profile was similar for both groups. The mean simK values were reduced from 46.93 ± 3.50 and 46.44 ± 2.93 preoperatively to 46.18 ± 3.65 and 45.54 ± 2.78 at 12 months postoperatively, for C-CXL and A-CXL, respectively ( P = .003 for both groups). The mean Kmax decreased from 52.46 ± 4.82 and 51.50 ± 3.87 preoperatively to 51.30 ± 4.42 and 50.30 ± 3.52 postoperatively, for the C-CXL and A-CXL, respectively ( P < .001 for both groups). There was no difference in the simK and Kmax changes between the C-CXL and A-CXL groups ( P = .814 and P = .913), visual acuity, and refraction between the 2 groups ( P > .05). CONCLUSIONS: A-CXL with a 20-minute riboflavin/HPMC soaking produced deeper DL and similar corneal haze, topographic, refractive, and visual results to C-CXL with a 30-minute riboflavin/dextran soaking.

Asymmetric All-Femtosecond Laser-Cut Corneal Allogenic Intrastromal Ring Segments.

PURPOSE: To describe a novel technique for cutting asymmetric allogenic segments using the femtosecond laser for the management of cases of keratoconus with non-coinciding astigmatism and coma axes. METHODS: Four eyes of 2 patients with irregular keratoconus and asymmetric allogenic segments were included. Visual, refractive, tomographic, and aberrometric outcomes, and optical coherence tomography (OCT) sections were measured preoperatively and 6 months postoperatively. Evaluations included slit-lamp examination, manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuity, and simulated and maximum anterior keratometry (Kmax) using anterior segment OCT. RESULTS: Spherical and cylindrical refractive errors decreased from -2.38 ± 2.96 and -2.94 ± 2.16 to -1.81 ± 2.77 (P = .04) and -1.75 ± 2.07 (P = .01) diopters (D), respectively, 6 months postoperatively. There was an average gain of three lines of CDVA. Kmax decreased from 50.02 ± 1.99 to 47.89 ± 3.05 D (P= .03) and coma from 1.05 ± 0.21 to 0.21 ± 0.19 D (P = .01). CONCLUSIONS: Asymmetric femtosecond laser-cut allogenic segments allow a higher level of customization based on size, shape, and arc length, in contrast to the limited range of available synthetic asymmetrical segments. [J Refract Surg. 2023;39(12):856-862.].

Corneal Allogenic Intrastromal Ring Segments (CAIRS) for Corneal Ectasia: A Comprehensive Segmental Tomography Evaluation.

PURPOSE: To evaluate the visual, refractive, and tomographic results of patients with corneal ectasia treated with corneal allogenic intrastromal ring segments (CAIRS) insertion without concomitant corneal cross-linking. METHODS: Fifty-two eyes from 39 patients with stable corneal ectasia and unsatisfactory visual acuity with contact lenses were included. All patients underwent CAIRS insertion with no concomitant corneal procedure at the American University of Beirut Medical Center between September 2019 and July 2022. Visual, refractive, topographic, aberrometric, epithelial, stromal, and segment thickness data were measured relative to baseline at 1 week, 1 month, and at least 3 months postoperatively. Evaluations included slit-lamp examination, manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuity, and tomography using anterior segment optical coherence tomography. RESULTS: Mean follow-up time was 6.9 ± 5.2 months. UDVA and CDVA improved from 0.97 ± 0.47 and 0.56 ± 0.19 preoperatively to 0.52 ± 0.21 (P < .001) and 0.23 ± 0.19 (P < .001) 3 months postoperatively. Manifest refraction spherical equivalent and cylinder improved from -6.71 ± 6.51 and -4.02 ± 2.24 diopters (D) preoperatively to -3.78 ± 4.07 D (P < .001) and -2.35 ± 1.98 D (P < .001) 3 months postoperatively, respectively. Maximum anterior keratometry and vertical coma decreased from 58.09 ± 7.92 D and 1.56 ± 1.09 µm to 52.48 ± 6.69 D (P < .001) and 0.43 ± 0.77 µm, respectively (P < .001). Corneal epithelium thickened proximal to the allogenic segment by 7.25 µm (P < .001), whereas stromal elevation at the cone decreased from 38.61 ± 18.5 to 23.82 ± 13.4 µm, respectively (P < .001). No major complications were observed and only 1 eye lost one line of CDVA. CONCLUSIONS: Treatment of corneal ectasia with CAIRS improved visual, refractive, topographic, and tomographic parameters. Epithelial thickening central to CAIRS, along with anterior stromal flattening is postulated to contribute to tomographic flattening and regularization. [J Refract Surg. 2023;39(11):767-776.].

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.

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.

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.

Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.

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.

Expanding indications for corneal cross-linking.

PURPOSE OF REVIEW: The aim of this study was to summarize the recent developments in corneal cross-linking (CXL) and its indications, including corneal ectasias, refractive surgery and infectious keratitis. RECENT FINDINGS: Advances in CXL technology, such as the use of higher-intensity LED ultraviolet (UV) light sources and a better understanding of the UV-riboflavin photochemical reaction, have enabled safer and more effective methods of cross-linking thin and ultra-thin corneas, and more effective accelerated transepithelial/'epi-on' CXL procedures that are beginning to supplant the Dresden protocol as the 'gold standard' CXL method. CXL is also being used in combination with laser surgery, not only to expand the patient base who can receive refractive surgery, but also to help rehabilitate vision in patients with ectasia. CXL, and CXL combined with photorefractive keratectomy (PRK), can result in corneal flattening of 1-2 D, and corneal regularization of 4-5 D, respectively. Finally, photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) has been shown to be an effective therapy for infectious keratitis, both alone, and in combination with antimicrobial drugs. SUMMARY: CXL has evolved from a single technique to treat a single corneal ectasia, keratoconus, to several techniques with several indications, spanning a spectrum of corneal ectasias, as well as visual rehabilitation, refractive procedures and infectious keratitis treatment.

TFOS Lifestyle: Impact of elective medications and procedures on the ocular surface.

The word "elective" refers to medications and procedures undertaken by choice or with a lower grade of prioritization. Patients usually use elective medications or undergo elective procedures to treat pathologic conditions or for cosmetic enhancement, impacting their lifestyle positively and, thus, improving their quality of life. However, those interventions can affect the homeostasis of the tear film and ocular surface. Consequently, they generate signs and symptoms that could impair the patient's quality of life. This report describes the impact of elective topical and systemic medications and procedures on the ocular surface and the underlying mechanisms. Moreover, elective procedures performed for ocular diseases, cosmetic enhancement, and non-ophthalmic interventions, such as radiotherapy and bariatric surgery, are discussed. The report also evaluates significant anatomical and biological consequences of non-urgent interventions to the ocular surface, such as neuropathic and neurotrophic keratopathies. Besides that, it provides an overview of the prophylaxis and management of pathological conditions resulting from the studied interventions and suggests areas for future research. The report also contains a systematic review investigating the quality of life among people who have undergone small incision lenticule extraction (SMILE). Overall, SMILE refractive surgery seems to cause more vision disturbances than LASIK in the first month post-surgery, but less dry eye symptoms in long-term follow up.

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.

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.

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.

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.

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.