ELZA Institute

To assess corneal resistance to enzymatic digestion after rose bengal (RB)/green light and RB/green light followed by riboflavin (RF)/ultraviolet A (UV-A) cross-linking (CXL), with or without oxygen. Ex vivo porcine corneal buttons (n = 144) underwent CXL with RB/green or RB/green-RF/UV-A under atmospheric 21% oxygen conditions or in a nitrogen chamber with 0.1% oxygen (hypoxic conditions) to test 10- and 15-J/cm2 fluences. After CXL, corneas were digested with 0.3% collagenase A, and mean digestion times (MDTs) were recorded. For the non-irradiated control group, the MDT was 19.75 ± 1.34 hours. Under atmospheric oxygen conditions, RB/green CXL yielded MDTs of 33.69 ± 1.4 and 34.38 ± 1.31 hours with fluences of 10 and 15 J/cm2, respectively. RB/green + RF/UV-A showed MDTs of 39.56 ± 1.93 and 51.94 ± 4.2 hours for combined fluences of 10 + 10 J/cm2 and 15 + 15 J/cm2, respectively. Hypoxic RB/green MDTs were 33.88 ± 1.02 and 34.06 ± 1.57 hours, and RB/green + RF/UV-A MDTs were 39.62 ± 2.5 and 50.35 ± 1.59 hours for the same respective fluences. No significant differences were observed between the control groups and corresponding intervention groups (all P > 0.05). CXL via RB/green and RB/green-RF/UV-A significantly enhanced corneal collagenase digestion resistance, irrespective of oxygen presence. These findings could help optimize infectious keratitis therapy CXL protocols. Our findings aid the understanding of the molecular mechanisms underlying the therapeutic effect of CXL and may contribute to refining accelerated PACK-CXL protocols and other CXL treatment strategies.

Keywords: cornea, medication, pharmacology, corneal cross linking, PACK-CXL, corneal neovascularization, corneal endothelial disease

To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. Eye Hospital of Wenzhou Medical University, Wenzhou, China. Retrospective case-control study. 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. 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. 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.

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.

PurposeTo determine whether high-fluence photoactivated chromophore for keratitis cross-linking (PACK-CXL) can be accelerated.MethodsSolutions 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).ResultsWith 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).ConclusionsThe 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 RelevanceThe high-fluence PACK-CXL protocols can be accelerated in clinical practice while maintaining high levels of BKR.

Corneal epithelium removal during photorefractive keratotomy (PRK), TransPRK, or corneal cross-linking (CXL) means that patients experience pain and inflammation after the procedure, which need to be carefully managed with topical drug regimens. One highly effective class of topical analgesics is non-steroidal anti-inflammatory drugs (NSAIDs), but these must be used carefully, as their use has been associated with delayed re-epithelialization and, in rare cases, corneal melting. However, our clinical experience has been that the concomitant use of topical corticosteroids obviates this risk. Here, we present a mechanistic explanation for our observations, our TransPRK and epithelium-off CXL protocols, and the postoperative medication regimens where topical NSAIDs are used in combination with topical steroid therapy during the first two postoperative days (where pain and inflammation levels are the highest). We detail the results of a single-center retrospective case analysis that examined eyes that underwent TransPRK (n = 301) or epithelium-off CXL (n = 576). Topical NSAID use in the first two postoperative days to control pain and inflammation after PRK/TransPRK or epithelium-off CXL, when used in combination with topical steroid therapy, does not appear to be associated with corneal melting or delayed epithelial healing. This approach may represent an improvement over current methods of handling post-surgical pain in procedures that require corneal epithelial debridement.