Faculty Bibliography

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.

PURPOSE/OBJECTIVE:We recently showed the positive clinical effects of combining accelerated corneal cross-linking (PACK-CXL) with antibiotic treatment in patients with presumed bacterial keratitis. In this study, we compare the impacts of a combined PACK-CXL/standard antibiotic treatment (PACK-ABX group) with standard antibiotic treatment alone (ABX group) in patients with culture-confirmed bacterial keratitis. METHODS:We reviewed patients with moderate and severe bacterial keratitis and confirmed bacterial cultures. Clinical outcomes were compared for standard antibiotic treatment alone, before the initiation of PACK-CXL, and after adjuvant use of PACK-CXL. RESULTS:A total of 47 eyes of 47 patients were included: 26 eyes in the PACK-ABX group and 21 eyes in the ABX group. Pathogens, baseline demographics (besides age), and clinical parameters were similar between the 2 groups. The PACK-ABX patients had better final uncorrected visual acuity [mean difference 0.57 Logarithm of the Minimum Angle of Resolution, 95% Confidence Interval (CI): 0.16-0.99, P = 0.07] and best-corrected visual acuity (mean difference 0.70 Logarithm of the Minimum Angle of Resolution, 95% CI: 0.23-1.16, P = 0.04), shorter reepithelialization time (mean difference 9.63 days, 95% CI: 3.14-16.12, P = 0.004), and reduced number of clinic visits (mean difference 4.8 meetings, 95% CI: 1.4-8.2, P = 0.007) and need for tectonic grafts (0 vs. 33.3%, P = 0.002). A multivariate analysis controlling for age, sex, ulcer size, and Gram stain showed that PACK-ABX treatment remained significantly associated with reepithelialization time (β = 14.5, P = 0.001). CONCLUSIONS:In our study, PACK-CXLs addition to the standard of care in cases of culture-proven bacterial keratitis had a positive effect on the final visual acuity and time to resolution, compared with the standard-of-care treatment.

PURPOSE/OBJECTIVE:To evaluate the effect of simulated repetitive eye rubbing on the corneal biomechanics of porcine eyes using an ex vivo model system. METHODS:The average rubbing force that patients with keratoconus apply to their eyelids was previously determined. Fresh porcine eyes with eyelids were either exposed to 10,500 rub cycles from a custom-built eye rubbing machine that rubbed with a similar force to knuckle human eye rubbing (n = 33) or no rubbing at all (control; n = 37). A total of 10,500 rubs are equivalent to 1 year of rubbing six times daily, five movements per rub. The corneal biomechanical properties of these eyes were then tested by measuring the elastic modulus of 5-mm strips. RESULTS:= .984). CONCLUSIONS:.

PURPOSE/OBJECTIVE:transepithelial enhanced fluence pulsed light M accelerated crosslinking in the treatment of progressive keratoconus (KC) with chemically enhanced hyper-concentrated riboflavin solutions without iontophoresis and with air-room oxygenation. SETTING/METHODS:Siena Crosslinking Center, Siena, Italy. METHODS:ACXL (EFPL M TECXL). The 12 min and 58 s pulsed light (1 s on/1 s off) UV-A exposure treatments were performed with a biphasic corneal soaking using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min riboflavin solutions and New KXL I UV-A emitter (Glaukos-Avedro, Waltham, USA) at an air room of 21% oxygenation. All patients completed the 3-year follow-up. RESULTS:CDVA showed a statistically significant improvement in the third postoperative month (Δ + 0.17 d. e.) with a final gain of +0.22 d. eq. AK showed a statistically significant decrease in the sixth postoperative month (Δ - 1.15 diopters). K itmax showed a statistically significant decrease at 1-year follow-up (Δ - 1.3 diopters). The coma value improved significantly by the sixth month (Δ - 0.54 µm). MCT remained stable during the entire follow-up. No adverse events were recorded. Corneal OCT revealed a mean demarcation line depth at 282.6 ± 23.6 μm. CONCLUSIONS:Transepithelial enhanced fluence pulsed light M accelerated crosslinking with chemically enhanced riboflavin solution halted KC progression in young adult patients without iontophoresis and no intraoperative oxygen supplementation addressing the importance of increased fluence.

PURPOSE/OBJECTIVE:The purpose of this study was to report a case of fungal keratitis resistant to standard-of-care antimicrobial treatment and successful resolution, thanks to the repeated high-fluence accelerated photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL). METHODS:This was a case report. RESULTS:A 79-year-old male patient with previous Descemet membrane endothelial keratoplasty presented with a corneal ulcer that was resistant to topical antimicrobial therapy and amniotic membrane placement. Fungal keratitis was diagnosed, and the cornea was on the verge of perforation. After over a month of topical and systemic therapy without marked improvement, the patient underwent 2 repeated high-fluence accelerated CXL procedures (7.2 J/cm2 using a UV irradiation of 30 mW/cm2 for 4 minutes) over an interval of 8 days (accumulated fluence of 14.4 J/cm2), which resulted in significant clinical improvement, with consolidation into a quiescent scar. CONCLUSIONS:PACK-CXL protocols delivering a total UV fluence of 5.4 J/cm2 (as per the original Dresden protocol for corneal ectasia cross-linking) can be an effective primary therapy for initial or superficial corneal infections because approximately half of the energy is absorbed in the first 100 μm of a riboflavin-soaked cornea. However, fungal keratitis may require higher fluences than 5.4 J/cm2 because, unlike ectatic corneas, corneal ulcers are not transparent, and the infection may involve deep stroma. This case illustrates how repeated high-fluence accelerated PACK-CXL can be used to successfully treat fungal keratitis resistant to conventional topical and systemic medications.

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.