Conjunctival Collagen Cross-Linking for the Treatment of Leaking Avascular Cystic Bleb.

Trabeculectomy is a primary surgical procedure used to reduce intraocular pressure (IOP) in patients with glaucoma. Despite its effectiveness, it can lead to significant complications, including hypotony, choroidal effusion, blebitis, and bleb leaks. Bleb leaks require prompt medical or surgical intervention to prevent severe complications such as blebitis and bleb-associated endophthalmitis. In recent years, the indications for collagen cross-linking (CCL) have expanded beyond corneal ectatic diseases to include various ocular conditions such as keratitis and leaking blebs. Here, we present the case of a 70-year-old male patient with a leaking avascular cystic bleb. Following treatment with a combination of conjunctival CCL, topical gentamicin, a dorzolamide/timolol combination, and a therapeutic contact lens, the patient experienced cessation of bleb leakage and an increase in IOP.

Progression of corneal thinning and melting after collagen cross-linking for keratoconus.

Objective: To study the aetiology, diverse clinical manifestations, therapeutic interventions, and prognoses in patients with corneal thinning after collagen cross-linking (CXL) treatment. Methods: a retrospective observational study of all patients presenting with corneal thinning after collagen cross-linking, in a tertiary eye care hospital in south India from 2011 to 2017. Preoperative details were noted. Patients who presented with corneal thinning were subjected to investigative measures to assess thinning, received appropriate management, and underwent follow-up evaluations. Results: Among the 12 patients, 8 were female and 4 were male, all of whom had undergone standard classical CXL. The duration between CXL and corneal melting/thinning onset varied from 5 to 12 years. Notably, among female patients, 2 were pregnant, 2 were lactating mothers, 1 was undergoing in vitro fertilization (IVF) treatment, and 1 had comorbid diabetes mellitus and hyperthyroidism. Clinical examination revealed corneal thinning accompanied by hypopyon in 1 patient, corneal perforation with shallow anterior chamber in 1 patient, and epithelial defect with crystalline deposit in another patient, the remaining patients exhibited corneal thinning. Corneal thinnest corneal thickness measurements ranged from 212 to 351 µm. Treatment approaches included penetrating keratoplasty (PKP) in 2 patients, deep anterior lamellar keratoplasty (DALK) in 1 patient, cyanoacrylate glue application in 1 patient, and awaiting DALK/PKP in three patients, 4 patients showing no signs of increased thinning. Conclusion: The incidence of corneal thinning after collagen cross-linking is less but fulminant, requiring timely and appropriate management to prevent visual complications.

Pediatric keratoconus in a tertiary eye hospital in Eastern province, Saudi Arabia: Patient characteristics and management outcomes.

PURPOSE: This study investigates pediatric keratoconus in a tertiary eye hospital in Eastern Province, Saudi Arabia, aiming to understand the presenting features and treatment outcomes in this high-prevalence region. The research addresses pediatric keratoconus clinical profile and management strategies. METHODS: A retrospective cohort study was conducted from 2022 to 2023, reviewing medical records of pediatric keratoconus patients. Demographic data, clinical characteristics, risk factors, presenting symptoms, and treatment outcomes were recorded. Severity staging was performed based on Amsler-Krumeich's classification. RESULTS: The study included 218 eyes from 109 pediatric keratoconus patients, with 65% of male and 35% of female patients. Decreased vision was the most common symptom (92%), and risk factors included a family history of keratoconus (9%) and vernal keratoconjunctivitis (6%). Stage 1 was the most frequent in both age groups (<14 years and ≥ 14 years). Treatment strategies included corneal collagen cross-linking (CXL), hard contact lenses, corneal rings, deep anterior lamellar keratoplasty (DLK), and penetrating keratoplasty. Significant improvements were observed in visual acuity, refractive errors, and tomographic parameters following these interventions. CONCLUSION: This study provides valuable insights into pediatric keratoconus in Saudi Arabia, emphasizing the importance of early diagnosis and interventions for better outcomes. Larger, multicenter prospective studies are essential for a comprehensive understanding of pediatric keratoconus and its optimal management. The findings contribute to the knowledge base and guide future research to improve patient quality of life.

Permeation characteristics and cross-linking efficacy of iontophoresis-assisted riboflavin delivery for accelerated riboflavin-ultraviolet A scleral collagen cross-linking in porcine eyes.

The purpose of this study is to investigate whether the iontophoresis-assisted riboflavin delivery to posterior sclera with less delivery time, can achieve the same riboflavin permeation efficiency as the passive soaking way, and its effect on the mechanical properties of posterior sclera for accelerated scleral collagen cross-linking (A-SXL). In this study, 0.1% riboflavin solution was applied into the posterior sclera of porcine eyes either by the iontophoresis-assisted or passive soaking method, with delivery time of 5, 7.5, 10, 12.5, 15, 17.5, and 20 min, respectively. The fluorescence intensity and the distribution of riboflavin concentration in the 10 µm frozen sections of the sclera were evaluated by fluorescence inverted microscope. The posterior sclera with riboflavin treatment through either the iontophoresis-assisted or the passive soaking method for different durations ranging from 5 to 20 min was treated with ultraviolet A (UVA) irradiation at an intensity of 10 mW/cm2 for 9 min. The elastic modulus was determined at the physiological strain level using the uniaxial tensile test after ASXL. The results showed that the fluorescence intensity of riboflavin increased by prolonging the delivery time in both the iontophoresis and passive soaking groups, and the permeation depth of riboflavin remained constant over 15 min. The fluorescence intensity in the iontophoresis group was significantly higher than in the passive soaking group at 12.5 min and 15 min, respectively. The elastic modulus at 12.5 min in the iontophoresis group was significantly higher than in the passive soaking group at the same delivery time and showed no significant difference compared to the passive soaking group at 20 min. In conclusion, it indicated that iontophoresis-assisted delivery could not only shorten the surgery time but also achieve similar mechanical performance to the passive soaking method in ASXL.

The Utilization of Brillouin Microscopy in Corneal Diagnostics: A Systematic Review.

Corneal biomechanical data has been used since 2005 to screen for keratoconus and corneal ectasia by corneal specialists. Older technology uses force applanation techniques over a 3 mm area in the central cornea, making it highly dependent on extraneous variables and unable to calculate the elasticity of the tissue. Brillouin microscopy is a newer method that uses a natural shift in the frequency of light as it passes through a material. This frequency shift can be used to estimate the viscoelasticity of the tissue. The advantage of Brillouin microscopy is that it can create a full three-dimensional (3D) map of the entire cornea without direct contact. A literature search was conducted using the databases PubMed, Google Scholar, and Ovid regarding the applications of Brillouin microscopy in corneal diagnostics. A final total of 16 articles was included describing the various ex vivo and in vivo studies conducted using Brillouin microscopy. Applications of this technology spanned from keratoconus diagnosis to post-corneal refractive surgery evaluation. All studies evaluated corneal biomechanics and other corneal properties through the quantification of Brillouin frequency shifts. Many of the studies found that this diagnostic device is capable of detecting subtle changes in corneal thickness and biomechanics in keratoconic corneas at a high level of specificity and sensitivity. However, limitations of Brillouin microscopy may include the duration of time required for use and fluctuations in accuracy depending on the corneal hydration state. Future technology seems to be geared toward a combination of optical coherence tomography (OCT) and Brillouin microscopy, using OCT as a three-dimensional pupil-tracking modality. Further research and understanding of the technology involved will lead to better care of patients in the field of ophthalmology.

Pulsed corneal crosslinking in the treatment of Keratoconus: a systematic review and meta-analysis.

PURPOSE: Corneal crosslinking (CXL) procedures are the treatment of choice in halting progressive corneal ectasia and preserving visual acuity due to keratoconus. Pulsed crosslinking (P-CXL) was developed using intermittent pulsing ultraviolet (UV) light to mitigate the depletion of oxygen levels that occurs with continuous UV exposure in standard crosslinking protocols (C-CXL). This study aimed to explore the use of P-CXL in the treatment of keratoconus and determine whether the availability of oxygen in P-CXL carries superior efficacy outcomes as an alternative to C-CXL modalities. METHODS: This review was undertaken in accordance with PRISMA guidelines. A search of several databases conducted with two separate reviewers resulted in 29 papers meeting inclusion criteria for the review, 14 selected for meta-analysis. Primary outcomes assessed by the included papers included maximum keratometry (Kmax), corrected and uncorrected distance visual acuity (CDVA, UDVA), and secondary outcomes included central corneal thickness (CCT), endothelial cell count and demarcation line. Statistical analyses were carried out on Review Manager 5.4 and the meta-analysis employed a random-effects model, which estimated the weighted effect size of raw means using inverse variance weights. RESULTS: At 12 months P-CXL showed statistically significant reductions in Kmax (-0.75 D; p < 0.001) and improvement in CDVA (-0.10 logMAR; p < 0.001) compared to baseline. The meta-analysis of comparative studies determined that mean differences in Kmax, CDVA, UDVA, Kmean and CCT after 12 months were not statistically significant between pulsed and continuous crosslinking groups. CONCLUSIONS: Overall, P-CXL is effective in improving visual acuity and keratometry outcomes in keratoconus. The meta-analysis did not show a statistically significant difference in Kmax and CDVA between P-CXL and C-CXL, indicating a non-inferiority of P-CXL. However, findings of the meta-analysis are limited by the fact that different energy levels and exposure times were used for P-CXL in comparison to C-CXL in some studies, making it unsuitable to determine whether the efficacy of CXL is improved by the use of pulsed light. KEY MESSAGES: What is Known • Pulsed crosslinking (P-CXL) uses intermittent UV light to prevent oxygen depletion when using higher energy protocols, unlike continuous UV exposure in standard continuous crosslinking (C-CXL). • This should theoretically enhance the efficacy of the treatment by maintaining higher oxygen levels that are crucial to the cross-linking process. • There are no systematic reviews or meta-analyses directly comparing the efficacy or safety of P-CXL to C-CXL. What is New • Meta-analysis revealed differences in keratometry between P-CXL and C-CXL groups with equivalent fluence (7.2 J/cm2) at 12 months were not statistically significant (Kmax -0.04 dioptres; p = 0.84). • Meta-analysis revealed differences in visual acuity between P-CXL and C-CXL groups with equivalent fluence (7.2 J/cm2) at 12 months were not statistically significant (CDVA -0.01 logMAR letters; p = 0.57). • The use of intermittent pulsing in higher energy CXL protocols renders statistically similar outcomes as continuous light exposure at equivalent fluence (7.2 J/cm2).

Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

INTRODUCTION: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. MATERIALS AND METHODS: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. RESULTS: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (ß = 0.923;p = 0.031). CONCLUSION: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Assessing the impact of different Urushiol primer solvents on dentin remineralization and bond strength.

OBJECTIVES: To investigate urushiol's potential as a dentin cross-linking agent, promoting remineralization of etched dentin and preventing activation of endogenous proteases causing collagen degradation within the hybrid layer. The goal is to improve bond strength and durability at the resin-dentin interface. METHODS: Urushiol primers with varying concentrations were prepared using ethanol and dimethyl sulfoxide (DMSO) as solvents. Dentin from healthy molars underwent grinding and acid etching for 15 s, followed by a 1min application of urushiol primer. After 14 and 28 days of remineralization incubation and remineralization were used to assess by Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR), Micro-Raman spectroscopy, X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), Vickers Hardness, Scanning Electron Microscopy (SEM), and Energy X-ray dispersive spectroscopy (EDS). The overall performance of urushiol primers as dentin adhesives was observed by microtensile bond strength (µTBS) testing and nanoleakage assessment. Investigated the inhibitory properties of the urushiol primers on endogenous metalloproteinases (MMPs) utilizing in situ zymography, and the cytotoxicity of the primers was tested. RESULTS: Based on ATR-FTIR, Raman, XRD, EM-EDS and Vickers hardness analyses, the 0.7%-Ethanol group significantly enhanced dentin mineral content and improved mechanical properties the most. Pretreatment notably increased the µTBS of restorations, promoted the stability of the mixed layer, and reduced nanoleakage and MMPs activity after 28 days. SIGNIFICANCE: The urushiol primer facilitates remineralization in demineralized dentin, enhancing remineralization in etched dentin, effectively improving the bonding interface stability, with optimal performance observed at a 0.7 wt% concentration of the urushiol primer.

Proanthocyanidin surface preconditioning of dental pulp stem cell spheroids enhances dimensional stability and biomineralization in vitro.

AIM: Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold-free microtissue-based dental pulp regeneration. Surface collagen cross-linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross-linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)-derived 3D cell spheroids. METHODOLOGY: Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross-linking. Microtissue viability was examined by live/dead staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA-preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA-preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F-actin expressions. PA-preconditioned macrotissues were subjected to histological analysis, including haematoxylin-eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP-1) expressions. RESULTS: PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse-section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP-1 expressions in macrotissues. Additionally, PA preconditioning induced higher F-actin and DSPP expression in microtissues, while inhibition of F-actin activity by cytochalasin B attenuated PA-induced dimensional change and DSPP upregulation. CONCLUSION: PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC-derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold-free tissue engineering applications in regenerative dentistry.

Successful Collagen Crosslinking in a Patient With Keratoconus and Systemic Scleroderma.

Scleroderma is an autoimmune disease that affects connective tissue. Keratoconus (KC) is a rare ocular condition that may appear alongside scleroderma. Contact lenses are an essential visual aid for KC patients, especially in advanced cases. However, scleroderma patients may face difficulties using them due to finger-related disabilities. Corneal collagen cross-linking (CXL) is a crucial treatment used to prevent corneal thinning and visual deterioration in progressive KC. However, the potential trigger of corneal melt and delayed healing following CXL in KC patients with scleroderma is a matter of concern. We present a case of a patient with KC and scleroderma who underwent CXL without any complications.

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.

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions: theoretical basis.

Keratoconus is an ectatic condition characterized by gradual corneal thinning, corneal protrusion, progressive irregular astigmatism, corneal fibrosis, and visual impairment. The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages, gas-permeable rigid contact lenses, scleral lenses, implantation of intrastromal corneal ring or corneal transplants for most advanced stages. In keratoconus cases showing disease progression corneal collagen crosslinking (CXL) has been proven to be an effective, minimally invasive and safe procedure. CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation, resulting in stromal crosslinks formation. The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models, from the original Dresden protocol to the most recent developments in the technique, reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols. Finally, the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes collagen cross-linking and ECM stiffening to induce liver fibrosis.

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (Plod2) is a key collagen lysyl hydroxylase mediating the formation of collagen fiber and stabilized collagen cross-links, and has been identified in several forms of fibrosis. However, the potential role and regulatory mechanism of Plod2 in liver fibrosis remain unclear yet. Mouse liver fibrosis models were induced by injecting carbon tetrachloride (CCl4) intraperitoneally. The morphology and alignment of collagen was observed under transmission and scanning electron microscopy, and extracellular matrix (ECM) stiffness was measured by atomic force microscopy. Large amounts of densely packed fibrillar collagen fibers produced by myofibroblasts (MFs) were deposited in fibrotic liver of mice reaching very large diameters in the cross section, accompanied with ECM stiffening, which was positively correlated with collagen-crosslinking. The expression of Plod2 was dynamically up-regulated in fibrotic liver of mouse and human. In MFs transfection of Plod2 siRNA made collagen fibers more orderly and linear aligned which can be easily degraded and protected from ECM stiffness. Administration of Plod2 siRNA preventatively or therapeutically in CCl4 mice reduced the average size of collagen bundles in transverse section, increased collagen solubility, decreases the levels of crosslinking products hydroxylysylpyridinoline and lysylpyridinoline, prevented ECM stiffening and alleviated liver fibrosis. Altogether, Plod2 mediates the formation of stabilized profibrotic collagen cross-links in MFs, leading to the alteration of collagen solubility and ECM stiffness, and eventually aggravates liver fibrosis, which provide potential target for the treatment of liver disease.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

Keratometric Outcomes after Simultaneous versus Sequential Intracorneal Ring Segment Implantation with Femtosecond Laser and Corneal Collagen Crosslinking in Egyptian Patients with Keratoconus and Ectasia.

Background: Keratoconus (KC) is degenerative corneal disorder, with central and paracentral thinning and corneal ectasia. For KC progressive cases, primary treatment included corneal collagen cross linking (CXL) to stabilize coning and intracorneal rings segment (ICRS) to correct visual acuity. Aim: The aim of the study is to assess efficacy and safety of ICRS and CXL on one session (Simultaneous) or two sessions (sequential) with maximum of 1 month apart. Patients and Methods: This Prospective Intervention Comparative research made at Armed forces hospital, Cairo, Egypt from January 2017 to December 2019. Forty patients (60 eyes) with mild to moderate KC were enrolled. Patients sorted into Simultaneous group includes 21 patients (30 eyes) undergo two procedures (ICRS then CXL) at the same session and Sequential group included 19 patients (30 eyes) undergo ICRS then CXL on two sessions with month apart. Patients followed up at end of 1st, 3rd, and 6th months. Assessment included changes in corrected corneal surface irregularities as minimum keratometric 1 (K1), maximum keratometric readings (K2), and mean keratometric (Km) readings. Results: Improvement of K1, K2, and Km in Simulations and Sequential groups achieved at end of 1st-, 3rd-, and 6th-month postoperative versus preoperative. Maximum improvement in Simulations and Sequential groups in K1 achieved at end of 6th and 1st months, in K2 at end of 3rd and 6th months and in Km at end of 1st and 3rd months. Conclusions: Combined ICRS and CXL act safely in one or two sessions and there are no statistically significant variations between results on both methods in keratometric readings.

Reactive Oxygen Species-Responsive Nanoparticles Toward Extracellular Matrix Normalization for Pancreatic Fibrosis Regression.

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

Advances in the Treatment of Keratoconus: Epithelial-On (EPI-On) Corneal-Collagen Cross-Linking (CXL) and CXL-Plus Procedures.

Keratoconus (KC) incidence is on the increase. The advent of corneal-collagen cross-linking (CXL) has revolutionized the management of KC. This systematic review looks at the efficacy and complications of two novel treatments within CXL: Epithelial-On (Epi-On) and CXL-plus procedures. Two separate literature searches were carried out up until July 1, 2021. Articles only published in the last two years were included to ensure that only the most recent articles were reviewed. A total of 15 articles were selected for this review. There were varied results regarding the efficacy of Epi-On. No significant difference was found between Epi-On and standard Epithelial-Off (Epi-Off) CXL. However, it was found that Epi-On was inferior to standard CXL in terms of reducing KMAX. There was a higher risk of progression in patients treated with Epi-On CXL, with an increased rate of patients requiring re-treatment due to the advancement of their KC. While some studies report CXL-plus procedures demonstrate long-term efficacy and safety, a considerable number of studies advise caution, reporting a significant deterioration in corrected distance visual acuity (CDVA). Consequently, a question persists regarding the safest and most efficacious approach, given the lack of robust large randomized controlled trials (RCTs) in the current literature.

Evaluation of Keratoconus Disease with Tear Cytokine and Chemokine Levels Before and After Corneal Cross-Linking Treatment.

OBJECTIVES: To compare tear cytokine and chemokine levels of keratoconus (KC) patients with controls to perceive etiology distinctly and to clarify the molecular changes after cross-linking (CXL). METHODS: Tear samples were gathered from 34 participants in this prospective study. Participants underwent anterior and posterior segment examinations with slit-lamp biomicroscopy. Patients were assessed by corneal topography before and 3 months after CXL. Flat (K1), steep (K2), and average keratometry (Kmean), cylinder (CYL), and central corneal thickness (CCT) values were evaluated. After 3 months from CXL, samples were re-collected, and comparisons were made with preoperative values. RESULTS: Levels of IFN-gamma, IL-8, IL-12, IL-17, TNF-α, IL-4 and IL-13 were detected higher in KC patients (p= 0.008, p= 0.047, p= 0.001, p= 0.001, p= 0.001, p= 0.001, p= 0.027, respectively). After CXL IL-4, IL-5, IL-6, IL-7, IL-8, TNF-α levels showed significant decrease (p= 0.005, p= 0.045, p= 0.010, p= 0.022, p= 0.001, p=0.002, respectively). As for the topographic measurements, postoperative CCT values were increased whereas Kmean reduced after CXL (p < 0.001, p = 0.015, respectively). (p= 0.001, p= 0.027, respectively).Our findings imply that inflammation plays a key role in the development of KC and that this link is influenced by CXL therapy.

Citation network analysis on keratoconus.

OBJECTIVE: The high incidence of keratoconus has caused its management, etiology, and pathogenesis to be controversial topics in the ophthalmology field. This study aims to analyze the relationship between the different publications and authors through citation networks, as well as to identify the research areas and determine the most cited article. METHODS: The search for publications was carried out through the Web of Science database, using the term "Keratoconus" between 1900 and December 2022. The Citation Network Explorer and CiteSpace software were used for the publication analysis. RESULTS: 9,655 publications were found, with 124,379 citations generated on the network. The year with the highest number of publications was 2021. The most cited publication was "Keratoconus" by Rabinowitz, published in 1998. Cluster function gave five groups of research areas about keratoconus: corneal signs and parameters, cross-linking efficiency and effects, clinical factors, keratoplasty, and treatment. CONCLUSIONS: The citation network offers an objective and comprehensive analysis of the papers on keratoconus.

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.