Hyperbaric Oxygenation Maintains Elevated Stromal Oxygen Availability During Corneal Collagen Crosslinking with and Without Epithelial Removal.

PURPOSE: Corneal collagen cross-linking (CXL) can halt corneal ectasia. Leaving corneal epithelium intact during treatment may reduce the incidence of complications. However, it is under debate whether this reduces efficacy and if oxygen supplementation may be necessary to optimize the cross-linking effect. This study aimed to investigate the impact of hyperbaric oxygenation (HBO) on intracorneal oxygen concentrations during epi-off and epi-on CXL. METHODS: CXL was performed using riboflavin and ultraviolet-A (UV-A) irradiance (3 mW/cm2 for 30 min) on porcine corneas under normobaric and hyperbaric conditions, with and without supplemented oxygen, with and without epithelium. Intracorneal oxygen concentrations were continuously monitored before and during irradiation. Biomechanical properties were assessed through tensile strength testing. RESULTS: HBO alone did not cause perceivable changes in stromal oxygen concentrations. Oxygen supplementation resulted in higher oxygen concentration in corneal stroma during CXL. HBO may cause a further increase in oxygen levels, although this was not statistically significant in this study. Notably, a tendency of oxygen levels to rise continuously during UV-irradiation was observed using HBO. Biomechanical properties showend no statistically significant differences between any groups. CONCLUSIONS: In this ex-vivo model, HBO increased stromal oxygen levels during CXL, regardless of the presence of corneal epithelium. The dynamics in oxygen concentrations in corneal stromal tissue during CXL suggest that time is an important factor to consider in modifications of established protocols. Also, we hypothesize that stromal levels of riboflavin and UV-A irradiance may be more critical to the CXL effect when oxygen is supplemented and epithelium is not removed.

The impact of interrupted corneal collagen crosslinking (CXL) treatment.

PURPOSE: To evaluate progression of keratoconus in patients where CXL treatment was interrupted due to insufficient swelling of the cornea. METHODS: A retrospective review was conducted of all patients with keratoconus diagnosis who underwent CXL at the Department of Ophthalmology, Örebro University Hospital (USÖ) during the years 2010-2017. In total 377 eyes of 280 patients were screened for inclusion. In 17 eyes (15 patients), the treatment was interrupted due to insufficient swelling of the cornea. Patient journals were reviewed and keratometry examinations were analysed for long-term progression. RESULTS: Eleven eyes (nine patients) were included in the study. Five eyes showed no signs of progression after the interrupted CXL treatment. In one eye progression continued, however, first after a period of a number of years, indicating a delayed course of clinical progression. CONCLUSION: This study indicates that debridement of the corneal epithelium and riboflavin administration without intense UVA radiation may slow or arrest the progression of keratoconus, likely due to photosensitisation from ambient light.

Efficacy and Safety of the Modified Cretan Protocol in Patients with Post-LASIK Ectasia

Objectives: To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE). Materials and Methods: In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment. Results: Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 µm, and -0.21±0.63 µm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 µm, and -0.51±0.58 µm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up. Conclusion: The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results.

[Alternative methods of surgical treatment of keratoconus]. / Al'ternativnye metody khirurgicheskogo lecheniya keratokonusa.

The introduction of early diagnostic methods for keratoconus into clinical practice has become the basis for the development of surgical treatment techniques for this pathology, such as corneal collagen crosslinking and interlamellar keratoplasty with implantation of intrastromal segments. The article analyzes the results of research by Russian and foreign specialists in these areas and presents the data on the combination of SMILE surgery and corneal crosslinking, the Rome protocol of corneal crosslinking, modifications of interlamellar keratoplasty, the use of femtosecond laser technologies, and some pilot studies. Modern requirements for ophthalmological care require a personalized approach to each patient, and therefore the surgeon should have a wide range of surgical methods of treatment applicable to different patient cohorts. The described methods of treatment, according to the authors, are the most promising.

RiTe conjugate mediated corneal collagen crosslinking, a novel therapeutic intervention for keratoconus - in vitro and in vivo study.

Corneal collagen crosslinking (CXL) is an effective method to halt the disease progression of keratoconus, a progressive corneal dystrophy leading to cone shaped cornea. Despite the efficacy of standard protocol, the concerning step of this procedure is epithelial debridement performed to facilitate the entry of riboflavin drug. Riboflavin, a key molecule in CXL protocol, is a sparsely permeable hydrophilic drug in corneal tissues. The present study has employed cell penetrating peptide (CPP), Tat2, to enhance the penetration of riboflavin molecule, and thereby improve currently followed CXL protocol. This study demonstrates approximately two-fold enhanced uptake of CPP riboflavin conjugate, Tat2riboflavin-5'Phosphate (RiTe conjugate), both in vitro and in vivo. Two different CXL protocols (Epi ON and Epi OFF) have been introduced and implemented in rabbit corneas using RiTe conjugate in the present study. The standard and RiTe conjugate mediated CXL procedures exhibited an equivalent extent of crosslinking in both the methods. Reduced keratocyte loss and no endothelial damage in RiTe conjugate mediated CXL further ascertains the safety of the proposed CXL protocols. Therefore, RiTe conjugate mediated CXL protocols present as potential alternatives to the standard keratoconus treatment in providing equally effective, less invasive and patient compliant treatment modality.

The effect of transepithelial corneal collagen cross-linking treatment on optical quality of the cornea in keratoconus: 12-month clinical results.

PURPOSE: To evaluate the effect of transepithelial corneal collagen crosslinking (CXL) treatment on the optical performance of the cornea at 12-month follow-up after CXL in patients with progressive keratoconus. METHODS: One hundred and ten eyes of 67 patients were included. The following corneal optical aberrations over the 4-mm-diameter pupil were recorded via Sirius dual-scanning corneal tomography: total, anterior and posterior amount of corneal higher order aberrations [HOAs], vertical coma, horizontal coma, vertical trefoil, oblique trefoil, and spherical aberration, and Strehl ratio of point spread function (PSF). RESULTS: There were significant improvements in mean root mean square error values for corneal total HOA, total coma, anterior HOA, anterior coma, and vertical coma following CXL (P > 0.05, for all). No significant changes were found in the posterior aberometric parameters. PSF value did not change after CXL (P > 0.05). The corneal topographic measurements not revealed a change in the mean simulated keratometry-1, simulated keratometry-2, and maximum keratometry compared with the baseline measurements (P > 0.05, for all). At 12 months, there was a significant improvement in the uncorrected (UCVA) and best corrected (BCVA) visual acuity (P < 0.001, both). Most corneal aberrations correlated significantly with postoperative BCVA, but changes in HOAs were not statistically associated with improvements in visual acuity. CONCLUSIONS: Transepithelial CXL was effective in stabilizing the keratometric indices and improving the most corneal aberrations in keratoconic eyes 1 year after the procedure. While the healing effect on aberrations after CXL was in total and anterior parameters, no significant changes were observed in the posterior surface. In addition, it was observed that transepithelial CXL treatment did not cause a significant change in PSF distribution data.

Trends and Sociodemographic Patterns in Keratoconus Management 2015-2020: An American Academy of Ophthalmology IRIS® Registry Analysis.

PURPOSE: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age from 2015 to 2020 and evaluate sociodemographic associations with the treatment approach. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS® Registry (Intelligent Research in Sight). METHODS: Associations between sociodemographic factors and treatment were evaluated using multivariable logistic regression. MAIN OUTCOME MEASURES: Outcomes included percentages and rates of each treatment (collagen crosslinking [CXL], keratoplasty, or no procedure) from 2015 to 2020, age at diagnosis during this period, and sociodemographic factors associated with treatment type. RESULTS: A total of 66 199 patients with a new diagnosis of KCN were identified. The percentage of patients undergoing CXL increased from 0.05% in 2015 to 29.5% in 2020 (P = 0.008). The average age (standard deviation) of KCN patients decreased from 44.1 (±16.9) years in 2015 to 39.2 (±16.9) years in 2020 (P < 0.001). In multivariable analyses comparing CXL versus no procedure and keratoplasty versus no procedure, patients undergoing CXL tended to be younger with the odds of having CXL decreasing with increasing age, for example, comparing CXL and no procedure patients, using ages 0-20 years as reference, the odds ratio (OR) (95% confidence interval [CI]) decreased from 0.62 (0.57-0.67; P < 0.0001) for patients aged 21-40 years to 0.03 (0.02-0.04; P < 0.0001) for patients aged > 60 years. Men were more likely than women to have CXL (OR, 1.31; 95% CI, 1.23-1.40; P < 0.0001) and keratoplasty (OR, 1.30; 95% CI, 1.19-1.42; P < 0.0001). Black patients were less likely than White patients to have CXL (OR, 0.70; 95% CI, 0.63-0.77; P < 0.0001) and more likely to have keratoplasty (OR, 2.24; 95% CI, 2.01-2.50; P < 0.0001). Likewise, Hispanic patients had higher odds of CXL (OR, 1.12; 95% CI, 1.00-1.24; P < 0.05) and keratoplasty (OR, 1.29; 95% CI, 1.12-1.50; P < 0.001) compared with non-Hispanic patients. Collagen crosslinking and keratoplasty also varied by region and insurance status. CONCLUSIONS: A significant increase in use of CXL was noted from 2015 to 2020. Sociodemographic differences in treatment among KCN patients may reflect differences in access, use, or care patterns, and future studies should aim to identify strategies to improve access for all patients. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Refractive surgical correction and treatment of keratoconus.

Keratoconus is an ectatic corneal disorder that causes severe vision loss. Surgical options allow us to correct, partially or totally, the induced refractive error. Intracorneal ring segments (ICRS) implantation represents a minimally invasive surgical option that improves visual acuity, with a high success rate and a low overall complication rate. Corneal allogenic ICRS consists of ring segments derived from allogenic eye bank-processed donor corneas. Selective topography-guided transepithelial photorefractive or phototherapeutic keratectomy combined with CXL is another way in selected cases to improve spectacles corrected distance visual acuity. The microphotoablative remodeling of the central corneal profile is generally planned by optimizing the optical zones and minimizing tissue consumption. Phakic intraocular lens (PIOL) implant is considered in patients with stable disease and acceptable anatomical requirements. The two types of pIOLs, depending on their implantation inside the eye, are anterior chamber-pIOLs, which fixate to the anterior surface of the iris by using a polymethomethacrolate claw at the two haptics, and posterior chamber-pIOLs. In patients with both cataracts and keratoconus, the correct IOL power is difficult to obtain due to the irregular corneal shape and K values. Toric IOL is recommended, but carefully judging the topography and the possible need of subsequent keratoplasties.

Corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking for severe keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking(SC-A-TE-CXL)in the treatment of severe keratoconus.METHODS: Prospective before-after self-control study. A total of 10 cases(14 eyes)of severe keratoconus with the thinnest corneal thickness(including epithelium)less than 400 μm were collected from March 2019 to July 2022 at the ophthalmology department of Affiliated Eye Hospital of Nanjing Medical University. Among them, 8 males(12 eyes)and 2 females(2 eyes)were treated with SC-A-TE-CXL. Corneal curvature, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), the thinnest corneal thickness(TCT), central corneal thickness(CCT), non-contact intraocular pressure, endothelial cell density(ECD)and anterior or posterior elevations at the thinnest point before surgery and at 1, 3, 6 and 12 mo postoperatively were observed and recorded, as well as corneal cross-linking depth at 1 mo postoperatively.RESULTS: UCVA and BCVA at 1, 3, 6, and 12 mo after SC-A-TE-CXL were higher than those preoperatively, but there were no differences(F=0.793, P=0.535; F=0.783, P=0.542). K1, K2, Km and Kmax decreased at each time point postoperatively compared with those preoperatively, but there were no differences(F=0.627, P=0.574; F=1.264, P=0.296; F=0.727, P=0.520; F=1.115, P=0.359). Anterior and posterior elevations at the thinnest point both decreased compared with those preoperatively, but the differences were not statistically significant(F=1.046, P=0.359; F=1.164, P=0.337). The non-contact intraocular pressure at each time point postoperatively was higher than that preoperatively, but the differences were not statistically significant(F=0.814, P=0.522). There were no differences in CCT and TCT at any time points of the follow-ups compared with those preoperatively(F=0.931, P=0.453; F=0.782, P=0.542). There was no difference in ECD at 12 mo postoperatively versus preoperative value(t=1.266, P=0.228). At 1 mo postoperatively, anterior segment optical coherence tomography(AS-OCT)exhibited an increase of density in the anterior stroma, and there was a demarcation line with an average depth of 124.07±25.13 μm.CONCLUSION: SC-A-TE-CXL can be considered as a surgical treatment for severe keratoconus, which can delay the progression of severe keratoconus with high safety. However, the long-term efficacy of this treatment requires further observation.

Impact on quality of life of keratoconus patients treated with accelerated "epi-on" corneal collagen crosslinking technique: results from the NEI VFQ-25 Questionnaire in a Romanian population.

Objective: The main objective of this study was to describe vision-related quality of life (VRQoL) in a Romanian population of patients with keratoconus who underwent the accelerated "epi-on" corneal collagen crosslinking procedure and to evaluate the association with demographic data of age, gender and civil status (married, cohabitants or non-cohabitants). Method: The National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) was administered to 72 patients with keratoconus who had undergone a minimally invasive procedure. Descriptive statistics and bivariate analysis were used to determine the distribution of demographic parameters and a possible association between this parameter and the scores obtained on the NEI VFQ-25 questionnaire. Results: Based on the answers to the questionnaire we calculated the mean (SD) VFQ-25 total score, which was 73,97 (15,11), whilst scores for the subscales varied from 49.93 to 84,23. No significant difference was observed between the demographic parameters and the NEI VFQ-25 items, except for one item (being with others) when comparing paired and non-paired participants. Conclusion: In a Romanian population with keratoconus being treated with accelerated "epi-on" corneal collagen crosslinking procedure, VRQoL was reported at a high baseline level. The value of this information is significant when discussing patients' expectations during treatment. The VRQoL was not affected by age or civil status.

Paediatric cornea crosslinking current strategies: A review.

Background: In the general population, 1 in 2000 people has keratoconus. Indians and other people from Southeast Asia have a higher incidence of keratoconus. Children with keratoconus typically present earlier in life and with a more severe disease. Rubbing the eyes has been identified as a risk factor. Children have a higher incidence and a faster rate of keratoconus progression. Visual rehabilitation in children with keratoconus is challenging. They have a low compliance with contact lens use. Many of these children require penetrating keratoplasty at an early age. Therefore, stopping the progression of keratoconus in children is of paramount importance. Main text: Compared to treatment, keratoconus progression prophylaxis is not only preferable, but also easier. Corneal collagen cross-linking has been shown to be safe and effective in stopping its progression in children. The Dresden protocol, which involves central corneal deepithelization (7-9 â€‹mm), saturation of the stroma with riboflavin (0.25%), and 30 â€‹min UV-A exposure, has proven to be the most successful. Two significant disadvantages of the typical Dresden regimen are the prolonged operating time and the significant post-operative pain. Accelerated-CXL (9 â€‹mW/cm2 x 10 â€‹min) has been studied to reduce operative time and has been shown to be equally effective in some studies. Compared to accelerated CXL or traditional CXL, epi-off procedures, transepithelial treatment without the need for de-epithelialization and without postoperative discomfort, have been shown to be safer but less effective. Corneal crosslinking should only be performed after treating children with active vernal keratoconjunctivitis. Corneal opacity, chronic corneal edema, sterile infiltrates, and microbial keratitis have been reported after cross-linking of corneal collagen. Conclusions: The "Dresden protocol", also known as the conventional corneal cross-linking approach, should be used to halt the progression of keratoconus in young patients. However, if the procedure needs to be completed more rapidly, accelerated corneal crosslinking may be considered. Transepithelial corneal cross-linking has been proven to be less effective at stabilizing keratoconus, although being more safer.

Managing Corneal Infections: Out with the old, in with the new?

There have been multiple reports of eye infections caused by antibiotic-resistant bacteria, with increasing evidence of ineffective treatment outcomes from existing therapies. With respect to corneal infections, the most commonly used antibiotics (fluoroquinolones, aminoglycosides, and cephalosporines) are demonstrating reduced efficacy against bacterial keratitis isolates. While traditional methods are losing efficacy, several novel technologies are under investigation, including light-based anti-infective technology with or without chemical substrates, phage therapy, and probiotics. Many of these methods show non-selective antimicrobial activity with potential development as broad-spectrum antimicrobial agents. Multiple preclinical studies and a limited number of clinical case studies have confirmed the efficacy of some of these novel methods. However, given the rapid evolution of corneal infections, their treatment requires rapid institution to limit the impact on vision and prevent complications such as scarring and corneal perforation. Given their rapid effects on microbial viability, light-based technologies seem particularly promising in this regard.

Outcomes of two different treatment modalities in mild to moderate keratoconus.

PURPOSE: To describe visual and refractive outcomes of intrastromal corneal ring segments (ICRS) and toric implantable collamer lenses (TICL) implantation in cases of mild and moderate keratoconus. METHODS: A prospective descriptive interventional case series. 40 eyes were allocated into two groups. First group (20 eyes) was treated with corneal collagen crosslinking (CXL) 1 month after ICRS implantation and the second group was treated using TICL after 1 year of CXL. RESULTS: Both groups showed statistically significant improvement in spherical equivalent, cylindrical refraction, uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) over the follow-up period. CONCLUSION: Both ICRS and TICL are effective in treatment of mid and moderate keratoconus with more predictable visual results with TICL.

Safety and Efficacy of Corneal Cross-Linking in Patients Affected by Keratoconus: Long-Term Results.

The present study evaluated the effectiveness and safety of corneal collagen cross-linking (CXL). A total of 886 eyes with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standard epithelium-off Dresden protocol. Visual outcomes, maximum keratometry (Kmax), demarcation line measurements, and complications were recorded. Visual outcomes and keratometric data were analyzed in a subgroup comprising 610 eyes. Uncorrected distance visual acuity (UDVA) improved from 0.49 ± 0.38 LogMAR to 0.47 ± 0.39 LogMAR (p = 0.03, n = 610) three years after the procedure, while corrected distance visual acuity (CDVA) improved from 0.15 ± 0.14 LogMAR to 0.14 ± 0.15 LogMAR (p = 0.007, n = 610). A significant reduction of Kmax from 56.28 ± 6.10 to 54.98 ± 6.19 (p < 0.001, n = 610) was observed three years after CXL. In five eyes (0.82%, 5/610) keratoconus progression continued after CXL. Three eyes were retreated successfully with documented refractive and topographic stability after five years. In the 35 eyes that completed 10 years of follow-up, mean visual acuity and topographic parameters remained stable. In conclusion, CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure.

[Analysis of the results of modified personalized topographically and tomographically oriented technique of ultraviolet corneal collagen crosslinking]. / Analiz rezul'tatov modifitsirovannoi personalizirovannoi topograficheski i tomograficheski orientirovannoi metodiki ul'trafioletovogo krosslinkinga rogovichnogo kollagena.

PURPOSE: The study aims to develop a modified personalized topographically and tomographically oriented technique of ultraviolet corneal collagen cross-linking (UVCXL) to affect the area of the cornea with weakest biomechanical properties as determined by mathematical modeling. MATERIAL AND METHODS: Modeling of the biomechanics of keratoconic cornea under conditions of external diagnostic action was done using COMSOL Multiphysics® software. Finite-element analysis procured 3D images of stress/deformation distribution pattern throughout the cornea. Matching these 3D images with primary topographic and tomographic Pentacam AXL maps and Corvis ST findings allowed determining localization and dimensions of impaired regions of the cornea. The acquired data helped develop the modified corneal collagen cross-linking technique, which was applied in the treatment of 36 persons (36 eyes) with degrees I and II keratoconus. RESULTS: Uncorrected and best-corrected visual acuity (UCVA and BCVA logMAR) in all patients after modified UVCXL increased after the follow-up period lasting 6-12 months by 0.2±0.19 (23%) and 0.1±0.14 (29%) (p<0.05), respectively, in comparison with preoperative values. Maximum keratometry (Kmax) decreased by 1.35±1.63% (3%; p<0.05) in all cases at 6-12 months follow-up. Improvement of corneal biomechanical strength was determined by statistically significant increase in corneal stiffness index (SP-A1) and corneal stress-strain index (SSI) measured with Pentacam AXL and Corvis ST at 6-12 months follow-up by 15.1±5.04 (18%) and 0.21±0.20 (23%) (p<0.05), respectively. Effectiveness of the developed UVCXL technique is also confirmed by the appearance of a characteristic morphological marker - «demarcation line¼ at the cross-linking site in keratoconus projection at the depth of 240±10.2 µm. CONCLUSION: The developed personalized topographically and tomographically oriented UVCXL technique provides an evident stabilizing effect on the cornea in the form of an increase in its biomechanical strength, improvement of clinical, functional indicators and safety of keratoconus treatment.

Efficacy, Safety, and Outcomes following Accelerated and Iontophoresis Corneal Crosslinking in Progressive Keratoconus.

PURPOSE: To investigate the outcomes of accelerated (A-CXL) and iontophoresis (I-CXL) corneal crosslinking in a large retrospective cohort with progressive keratoconus. METHODS: This retrospective observational cohort study included consecutive patients treated by A-CXL (9 mW/5.4 J/cm2) or I-CXL with a minimal follow-up of 12 months. Visual acuity, manifest refraction, topography, specular microscopy, and corneal optical coherence tomography (OCT) were evaluated at baseline and at the last visit. Progression was defined as an increase in the maximum topographic keratometry (Kmax) of 1D. RESULTS: 302 eyes of 241 patients with a mean age of 25.2 ± 7.5 years were included from 2012 to 2019: 231 and 71 eyes in the A-CXL and I-CXL groups, respectively. The mean follow-up was 27.2 ± 13.2 months (maximum: 85.7 months). Preoperatively, the mean Kmax was 51.8 ± 4.0D, with no differences between groups. Mean topographic measurements and spherical equivalent remained stable during the follow-up. At the last visit, CXL failure was reported in 60 eyes (19.9%): 40 (14.7%) versus 20 (28.2%) in A-CXL versus I-CXL, respectively, p = 0.005. The likelihood of progression after CXL was significantly higher following I-CXL: RR = 1.62, CI95 = [1.02 to 2.59], p = 0.04. Demarcation line presence at 1 month was positively correlated with higher efficacy of CXL, p = 0.03. No endothelial damage was reported, especially in 51 thin corneas (range = 342-399 µm). CONCLUSIONS: A-CXL seems more effective than I-CXL in stabilizing keratoconus; this is to be taken into account when a therapeutic indication is posed according to the aggressiveness of the keratoconus.

A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases.

Infectious keratitis is a vision-threatening microbial infection. The increasing antimicrobial resistance and the fact that severe cases often evolve into corneal perforation necessitate the development of alternative therapeutics for effective medical management. Genipin, a natural crosslinker, was recently shown to exert antimicrobial effects in an ex vivo model of microbial keratitis, highlighting its potential to serve as a novel treatment for infectious keratitis. This study aimed to evaluate the antimicrobial and anti-inflammatory effects of genipin in an in vivo model of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) keratitis. Clinical scores, confocal microscopy, plate count, and histology were carried out to evaluate the severity of keratitis. To assess the effect of genipin on inflammation, the gene expression of pro- and anti-inflammatory factors, including matrix metalloproteinases (MMPs), were evaluated. Genipin treatment alleviated the severity of bacterial keratitis by reducing bacterial load and repressing neutrophil infiltration. The expression of interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 15 (IL15), tumor necrosis factor-α (TNF-α), and interferon γ (IFNγ), as well as MMP2 and MMP9, were significantly reduced in genipin-treated corneas. Genipin promoted corneal proteolysis and host resistance to S. aureus and P. aeruginosa infection by suppressing inflammatory cell infiltration, regulating inflammatory mediators, and downregulating the expression of MMP2 and MMP9.

Three-years outcomes of simultaneous photorefractive surgery and customized corneal cross-linking for keratoconus.

PURPOSE: To report the efficacy of customized cross-linking (CXL) in halting progression of keratoconus when combined with photorefractive procedures. METHODS: Seven eyes from 7 patients with documented progressive keratoconus were treated with customized CXL (customized ultraviolet-A irradiance pattern centered on the maximum posterior elevation with total energy levels ranging from 5.4 up to 10 J/cm2 , and an energy fluence of 9 mW/cm2) combined with photorefractive procedures. Four patients underwent simultaneous transepithelial photorefractive keratectomy (T-PRK) plus customized CXL, and three patients underwent simultaneous transepithelial phototherapeutic keratectomy (T-PTK) plus customized CXL. Tomographic parameters (Kmax, pachymetry of the thinnest point and maximal elevation of posterior float and regularization index) and best spectacle-corrected visual acuity (BSCVA) were compared preoperatively and 3 years postoperatively. RESULTS: All eyes showed a decrease in the maximal curvature Kmax, and none of eyes showed progression. Six eyes showed a flattening of 3 or more diopters (D). On average, Kmax decreased by - 4.8 ± 2.5 D, and the BSCVA improved by 0.04 ± 0.07 logarithm of the minimal angle of resolution. The mean value of regularization index was 8.7 ± 3.8 D. Mild corneal haze occurred in two eyes, and superficial apical scar occurred in one eye. None of the eyes had a vision-threatening complication. CONCLUSION: Customized CXL combined with photorefractive procedure (T-PRK/T-PTK) resulted in long lasting flattening effect and strong regularization of keratoconic corneas along with improvement of BSCVA over a 3-year follow-up.

The Keratectasia Volume (KEV) in Corneal Topography to Evaluate the Effect of Corneal Collagen Cross-linking in Pediatric Keratoconus.

The study aimed to evaluate the keratectasia volume (KEV) before and after corneal cross-linking (CXL) in pediatric patients. This study included 40 eyes of 25 pediatric patients (10-19 years) undergoing standard CXL. The support vector machine (SVM) algorithm was applied to transform mass pixels in corneal topography into a three-dimensioned model to calculate the KEV. The KEV, Kmax, K1, K2, Kave, keratectasia area (KEA), and thinnest corneal thickness (TCT) were determined before CXL and at 3, 6, and 12 months after surgery. The correlation between KEV and other parameters (Kmax, TCT, max decentration, eccentricity, and so on) was calculated. The KEV was 4.75 ± 0.74 preoperatively and 4.43 ± 1.22 postoperatively at last follow-up (p < 0.002). There was strong positive correlation between the KEV and Kmax (r = 0.806, p < 0.0005). The preoperat ive KEV was 4.32 ± 0.69 in mild to moderate keratoconus (Kmax < 58D) and 5.27 ± 0.37 in advanced keratoconus (Kmax > 58D) (p < 0.0005, t-test). Postoperative KEV and K readings remained stable at the early stage, and the KEV showed a more drastic decreasing trend than Kmax at sixth month. Statistical significance was found in the KEV between preoperative and 6 months after surgery (p < 0.0005), but not in Kmax and other parameters. In 83.3% (15 eyes out of 18 eyes) of the eyes, the preoperative KEV was greater than 4.6 in patients with significant flattening after CXL. Compared with K readings, the KEV can be regarded as a more sensitive index to evaluate the postoperative morphological changes after CXL in pediatric patients.

Network meta-analysis comparing efficacy and safety of different protocols of corneal cross-linking for the treatment of progressive keratoconus.

PURPOSE: This study aimed to determine the preferred protocol of corneal collagen cross-linking (CXL) in the treatment of progressive keratoconus. METHODS: Relevant studies were retrieved in PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL). Maximum keratometry value (Kmax), best spectacle-corrected visual acuity (BSCVA), manifest refraction spherical equivalent (MRSE), and endothelial cell density (ECD) were evaluated in network meta-analysis. RESULTS: Eight randomized controlled trials (RCTs) were included. Low-level evidence suggested that aCXL with 30mW/cm2 for 3 min (aCXL-3) might be the best protocol for reducing BSCVA (65.22%) but worst protocol for reducing MRSE (51.53%). aCXL with 18mW/cm2 for 5 min (aCXL-5) might be the best protocol for reducing Kmax (39.58%) and MRSE (77.85%) but might be the worst for preserving ECD (50.98%). aCXL with 9mW/cm2 for 10 min (aCXL-10) might be the best protocol for preserving ECD (31.53%). CONCLUSION: Overall, three protocols of aCXL are comparable in therapeutic efficacy and safety for treating progressive keratoconus. Despite no direct data comparing the efficacy of each technique according to different patients' profiles, it is reasonable to state that aCXL-5 may be the best for patients at early-stage to reduce Kmax and MRSE, aCXL-3 may be the best for patients at mid-stage to improve BSCVA, and aCXL-10 may be the best for patients at late-stage to preserve DEC.