Evaluation of the results of contact lens assisted corneal cross-linking treatment in keratoconus patients with thin corneas.

PURPOSE: We aimed to compare the efficacy and safety of accelerated contact lens-assisted cross-linking (CA-CXL) with Lotrafilcon B and Comfilcon A lenses in keratoconus (KC) patients with thin corneas. STUDY DESIGN: Retrospective, single-center study. MATERIALS AND METHODS: We retrospectively included 51 eyes of 39 KC patients with corneal thickness <400µm after epithelial scraping (Epi-off), who underwent accelerated CA-CXL treatment with Lotrafilcon B (n=20) and Comfilcon A (n=31). Uncorrected and corrected distance visual acuity (UDVA and CDVA), manifest refraction values, corneal topographic data and endothelial cell density were recorded at preoperative and postoperative 1st, 3rd and 6th month controls. RESULTS: CDVA in the Comfilcon A group was higher than CDVA before surgery at 6 months postoperatively (p<0.001). When the two lenses were compared, CDVA was found to be significantly higher in the Lotrafilcon B group in the preoperative, postoperative 1st month and 3rd month values, but there was no significant difference between the postoperative 6th month values (p=0.028, p=0.018, p=0.044, p=0.181, respectively). The maximum keratometry (Kmax) value at the 6th month after surgery in the Comfilcon A group was significantly lower than in the Lotrafilcon B group (p=0,009). There was no significant difference between the endothelial cell density values between the groups (p=0.623, p=0.609, p=0.794, p=0.458, respectively). There was no significant difference between the progression, regression, and stability rates of the two groups (p=0.714). CONCLUSIONS: Accelerated CA-CXL with Lotrafilcon B and Comfilcon A silicone hydrogel lenses is a safe and effective method to stop progression in patients with thin corneas.

Comparative evaluation of biomechanical changes and aberration profile following accelerated collagen cross-linking using hypo-osmolar and iso-osmolar riboflavin: A prospective study.

PURPOSE: To compare the changes encountered in corneal biomechanics and aberration profile following accelerated corneal collagen cross-linking (CXL) using hypo-osmolar and iso-osmolar riboflavin in corneal thicknesses of <400 and >400 microns, respectively. METHODS: This is a prospective, interventional, comparative study involving 100 eyes of 75 patients with progressive keratoconus. Eyes were divided into two groups based on corneal thickness: group 1 included eyes with a corneal thickness of <400 microns who underwent hypo-osmolar CXL, and group 2 included eyes with a corneal thickness of >400 microns who underwent iso-osmolar CXL. Corneal biomechanical and aberration profiles were evaluated and compared between groups. RESULTS: In group 1, all higher-order aberrations (HOA) except secondary astigmatism significantly decreased from baseline; however, in group 2, only coma and trefoil decreased. The corneal resistance factor and corneal hysteresis significantly improved in both groups, which was significantly greater in group 2 than in group 1. The change in inverse radius, deformation amplitude, and tomographic biomechanical index was significantly improved in group 2 as compared to group 1. CONCLUSION: Improvement in corrected distance visual acuity and decrease in HOA were significantly better in the hypo-osmolar CXL group; however, the improvement in biomechanical strength of the cornea was significantly better in the iso-osmolar group.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

PURPOSE: To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). METHODS: Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18 years) and adult (> 18 years). All of them were managed with epi-OFF ACXL (30 mW/cm2, 8 min, pulsed 1:1 on and off = 7.2 J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12 months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. RESULTS: Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15 years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. CONCLUSIONS: Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

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.

Sensory neuropathy as a manifestation of multiple acyl-coenzyme A dehydrogenase deficiency.

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder which typically manifests with muscle weakness. However, despite late-onset MADD being treatable, it is often misdiagnosed, due in part to the heterogeneity of presentations. We report a case of late-onset MADD manifesting first as a sensory neuropathy before progressing to myopathic symptoms and acute metabolic decompensation. Early diagnostic workup with acylcarnitine profiling and organic acid analysis was critical in patient outcome; metabolic decompensation and myopathic symptoms were completely reversed with riboflavin supplementation and dietary modification, although sensory neuropathy persisted. Clinical consideration of MADD as part of the differential diagnosis of neuropathy with myopathy is crucial for a timely diagnosis and treatment of MADD.

High-Fluence Epithelium-off Accelerated Pulsed Corneal Cross-linking (15 mW/cm2; 7.2 J/cm2) for Pediatric Keratoconus: A 3-Year Retrospective Analysis.

PURPOSE: To assess the safety and efficacy of treatment and secondarily determine the topographic changes, visual outcomes, and demarcation line depth after high-fluence pulsed light accelerated cross-linking (ACXL) in pediatric patients (younger than 18 years) with progressive keratoconus. METHODS: This retrospective analysis included 32 eyes (25 children, aged 11 to 18 years), with progressive keratoconus treated with high-energy epithelium-off pulsed light ACXL (7.2 J/cm2, 15 mW/cm2, 12 minutes, 2 seconds on/1 second off). Corrected distance visual acuity (CDVA), Scheimpflug tomography, and anterior optical coherence tomography measurements were recorded preoperatively and 1, 2, and 3 years postoperatively. RESULTS: A total of 32 eyes were included. Significant CDVA improvement, pachymetry, and maximum keratometry reduction were found at all follow-up visits. Mean keratometric values remained stable, and astigmatism showed a mild worsening (< 0.25 D) with statistical significance at 1 and 3 years. Total aberration showed discordant results and coma aberration had a slight improvement without statistical significance. The demarcation line depth was 265 ± 26 µm. Three patients developed mild haze without visual acuity loss. None of the patients underwent a second CXL procedure. CONCLUSIONS: In pediatric patients, high-fluence epithelium-off pulsed light ACXL appears to be a safe and effective procedure to halt the progression of keratoconus, slightly improving the CDVA and keratometric values. [J Refract Surg. 2024;40(3):e148-e155.].

Oxygen-supplemented and topography-guided epithelium-on corneal crosslinking with pulsed irradiation for progressive keratoconus.

PURPOSE: To investigate the effects of customized topography-guided epithelium-on crosslinking (epi-on CXL) with oxygen supplementation on procedural efficacy and corrected distance visual acuity (CDVA) in patients with progressive keratoconus (KC) at 1 year. SETTING: Private eye clinic, Brisbane, Australia. DESIGN: Retrospective, single-center, nonrandomized case series. METHODS: Topography-guided epi-on CXL using the Mosaic system was performed on patients with progressive KC. Oxygen goggles; transepithelial riboflavin; and pulsed, high UV-A irradiance (1 second on, 1 second off; 30 mW/cm2) were applied to enhance oxygen kinetics and bioavailabilities of riboflavin and UV-A. Guided by baseline topography, a higher UV-A dose (15 J/cm2) was applied to the area of steepest anterior curvature with decreasing fluence (as low as 7.2 J/cm2) toward the outer 9 mm. Postoperative CDVA and maximum keratometry (Kmax) were evaluated. RESULTS: 102 eyes (80 patients) were followed for 11.5 ± 4.8 months. At the latest follow-up, mean CDVA (logMAR), mean K, and Kmax (diopters [D]) improved from 0.18 ± 0.28, 46.2 ± 3.8, and 53.0 ± 5.67 at baseline to 0.07 ± 0.18, 45.8 ± 3.7, and 51.9 ± 5.56, respectively (P < .001). 3 eyes (3%) lost more than 1 CDVA line, and another 3 eyes (3%) had increased Kmax greater than 2 D. 43 eyes were followed for at least 12 months (n = 43): mean CDVA, mean K, and Kmax improved from 0.19 ± 0.33 logMAR, 46.5 ± 3.5 D, and 53.6 ± 5.67 D to 0.07 ± 0.17 logMAR, 46.0 ± 3.5 D, and 52.33 ± 5.49 D, respectively (P ≤ .002). No complications were observed. CONCLUSIONS: Tailoring oxygen-supplemented epi-on CXL with differential UV-A energy distributions, guided by baseline topography, in patients with KC seems to be safe and effective. At 1 year, study reports sustained improved CDVA and corneal stabilization.

Outcomes after corneal crosslinking treatment in paediatric patients with keratoconus.

PURPOSE: This study aims to determine the efficacy and safety of accelerated corneal crosslinking in children with keratoconus. METHODS: The study enrolled 64 patients aged 16 years or younger, each contributing one eye for a total of 64 eyes for analysis. Participants underwent an accelerated form of corneal cross-linking with 15 min of ultraviolet A irradiation at a rate of 7 mW/cm2, resulting in a cumulative energy dose of 5.4 J/cm2. The primary outcome measures were best corrected visual acuity (BCVA) and corneal tomography at 6 and 12 months post-intervention. Parameters assessed included BCVA, spherical and cylindrical refraction, keratometry (K1 and K2), maximum keratometry (Kmax) and thinnest corneal thickness (TCT). These metrics were documented preoperatively and then again at 6 and 12 months postoperatively. In addition, any ocular or systemic conditions related to keratoconus were recorded for each participant. RESULTS: The results showed an improvement in BCVA at 12 months after surgery. K1 showed a decrease at both post-operative follow-ups while K2 remained constant throughout the observation period. Kmax showed a notable decrease at the 12 month postoperative follow-up. Although the TCT showed an initial decrease, it reached a stable state after 12 months of crosslinking. Refractive values remained stable at all subsequent examinations. Notably, no complications such as corneal opacity, non-healing epithelial defects or corneal infections occurred during the follow-up period. The most common ocular comorbidity was allergic conjunctivitis (34.4%). CONCLUSION: The findings suggest that accelerated corneal crosslinking treatment is effective in slowing or halting the progression of keratoconus. Furthermore, there were no persistent overt complications observed at 12 months after the procedure.

Accelerated Corneal Cross-linking in Pediatric Patients with Progressive Keratoconus: 12-Month Follow-up Results.

PURPOSE: To evaluate effectiveness and safety of accelerated corneal cross-linking (CXL) in the treatment of keratoconus in pediatric patients. SETTING: Tertiary care hospital. DESIGN: Retrospective observational study. METHODS: In this study, case series of patients 18 years old or younger with progressive keratoconus who underwent accelerated CXL were observed. All consecutive patients underwent accelerated CXL with setting of 9 mW/cm2 for 10-minute Ultraviolet-A radiation, corresponding to a total dose of 5.4 J/cm2. Preoperative and 12-month postoperative data including uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), keratometry (K) measurements, mean spherical, and cylindrical refraction were evaluated. RESULTS: The group consisted of 28 eyes from 14 patients (10 males and 4 females). Mean age of the patients was 16.9 years (11-18 years). UDVA did not change significantly from 0.71 ± 0.54 to 0.65 ± 0.43 logMAR (P = 0.41). BDVA improved significantly from 0.30 ± 0.35 to 0.21 ± 0.34 (P = 0.006). The steep K-value decreased from 48.4 ± 4.3 to 48.0 ± 4.6 diopters, but there was no significant change in steep K-value (P = 0.35). There was no significant change in flat and mean K-value (P > 0.05). Mean spherical and cylindrical refraction were not significantly altered (P > 0.05). One patient with vernal keratoconjunctivitis showed sterile peripheral corneal infiltrates. Patient was treated with topical corticosteroids, antibiotics, and artificial tears. CONCLUSION: The findings revealed that accelerated CXL is an effective and safe procedure that halts the progression of keratoconus in pediatric patients.

A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene.

Lipid storage myopathy (LSM) is a heterogeneous group of lipid metabolism disorders predominantly affecting skeletal muscle by triglyceride accumulation in muscle fibers. Riboflavin therapy has been shown to ameliorate symptoms in some LSM patients who are essentially concerned with multiple acyl-CoA dehydrogenation deficiency (MADD). It is proved that riboflavin responsive LSM caused by MADD is mainly due to ETFDH gene variant (ETFDH-RRMADD). We described here a case with riboflavin responsive LSM and MADD resulting from FLAD1 gene variants (c.1588 C > T p.Arg530Cys and c.1589 G > C p.Arg530Pro, FLAD1-RRMADD). And we compared our patient together with 9 FLAD1-RRMADD cases from literature to 106 ETFDH-RRMADD cases in our neuromuscular center on clinical history, laboratory investigations and pathological features. Furthermore, the transcriptomics study on FLAD1-RRMADD and ETFDH-RRMADD were carried out. On muscle pathology, both FLAD1-RRMADD and ETFDH-RRMADD were proved with lipid storage myopathy in which atypical ragged red fibers were more frequent in ETFDH-RRMADD, while fibers with faint COX staining were more common in FLAD1-RRMADD. Molecular study revealed that the expression of GDF15 gene in muscle and GDF15 protein in both serum and muscle was significantly increased in FLAD1-RRMADD and ETFDH-RRMADD groups. Our data revealed that FLAD1-RRMADD (p.Arg530) has similar clinical, biochemical, and fatty acid metabolism changes to ETFDH-RRMADD except for muscle pathological features.

Comparison of refractive surgeries (SMILE, LASIK, and PRK) with and without corneal crosslinking: systematic review and meta-analysis.

Corneal crosslinking (CXL) is used for treating keratoconus and post-laser in situ keratomileusis ectasia. However, refractive surgery is not usually performed with prophylactic CXL. Therefore, we performed a meta-analysis comparing outcomes of refractive surgeries with vs without prophylactic CXL. We systematically searched databases for studies comparing refractive surgeries for myopic correction with vs without prophylactic corneal crosslinking. Review Manager 5.4.1 was used to perform statistical analysis. We included 2820 eyes from 28 studies. Compared with refractive surgery alone, surgery with prophylactic CXL resulted in decreased central corneal thickness, corrected distance visual acuity logMAR, and safety and efficacy indices. There were no significant differences in postoperative uncorrected distance visual acuity of 20/20 or better at ≥12 months and other visual outcomes among both groups. More randomized controlled trials with standard crosslinking protocols are needed to analyze the prophylactic use of crosslinking with refractive surgeries.

Strachan's syndrome and riboflavin deficiency.

Strachan's syndrome comprises a triad of optic, auditory and painful sensory peripheral neuropathy. It has been recognised since the late 19th century and is presumed to result from nutritional deficiency. Patients present acute or subacutely after a period of systemic illness, weight loss or, most commonly, dietary restriction, especially veganism, which can cause riboflavin (vitamin B2) and vitamin B12 deficiencies. The syndrome is more common in people who are black British and often of Jamaican descent. We describe the clinical phenotype using a typical case example, review other endemic nutritional peripheral neuropathies and discuss the potential benefit of riboflavin as a treatment.

Clinical, Anatomical, and Densitometric Changes following Dresden vs. Accelerated Corneal Cross-Linking in Progressive Keratoconus.

BACKGROUND: To compare clinical, anatomical, and densitometric changes following Dresden (DCXL) vs. accelerated (ACXL) corneal UVA cross-linking (CXL; Avedro KXL, Geuder, Heidelberg, Germany) in progressive keratoconus (KC). METHODS AND MATERIAL: In this retrospective study, we analyzed 20 patients following DCXL (3 mW/cm², 30 min, 5.4 J/cm²) and 44 patients following ACXL (9 mW/cm², 10 min, 5.4 J/cm²) between January 2016 and February 2020. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), steepest keratometry (Kmax), keratoconus index (KI), thinnest pachymetry (Pthin), and corneal densitometry (CD) were measured before and 3, 6, 12, and 24 months after CXL. RESULTS: During the follow-up period, no changes in UCVA, BSCVA, Kmax, KI, or Pthin occurred. CCT significantly decreased 3 months after DCXL (p = 0.032) and ACXL (p = 0.006). At the 12- and 24-month follow-up, CCT remained decreased in the DCXL (p = 0.035, 0.036, respectively) but not in the ACXL group. At the 12-month follow-up, the reduction in CCT was significantly greater in DCXL compared to ACXL (p = 0.012). At the 3-, 6-, 12-, and 24-month follow-ups, we found a significant increase in the anterior stroma CD following DCXL (p = 0.019, 0.026, 0.049, 0.047, respectively) but not ACXL. The CD changes were localized in the central concentric zones (0.0 to 6.0 mm). No intra- or postoperative complications occurred. CONCLUSION: ACXL and DCXL effectively halted KC progression. ACXL proved to be a safe time-saving alternative to conventional DCXL. DCXL led to a reduction in CCT and an increment in the CD of the central anterior stroma during 24 months of follow-up.

Patterns in refractive error and treatment delay in keratoconus-An Australian study.

Keratoconus is the most common primary corneal ectasia and is associated with significant morbidity. In its early stages, keratoconus is often asymptomatic, making the identification of subclinical disease challenging. Refractive error is a parameter that is documented at most routine optometry visits, yet interestingly, changes in refraction of keratoconic patients over time have not yet been studied and compared with the general population. Early diagnosis of keratoconus facilitates timely referral for treatments such as corneal collagen cross-linking, which has been shown to slow disease progression. In this context, documenting delays between initial presentation to the optometrist and referral for collagen-cross-linking as well as comparing the trends in visual acuity and refractive error between keratoconic and non-keratoconic patients over time are particularly relevant.

Clinical, biochemical, and genetic spectrum of MADD in a South African cohort: an ICGNMD study.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. METHODS: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. RESULTS: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067-0.00084%. CONCLUSIONS: This study reveals the first extensive genotype-phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population.

Effect of vitamin B2, vitamin C, vitamin D, vitamin E and folic acid in adults with essential hypertension: a systematic review and network meta-analysis.

OBJECTIVES: The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023. OUTCOMES: The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline. RESULTS: A total of 23 studies comparing five vitamins (vitamin B2, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: -14.14 mm Hg, 95% credible intervals: -27.62 to -0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins. CONCLUSIONS: According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding. PROSPERO REGISTRATION NUMBER: CRD42022352332.

Glycosaminoglycans and collagen fibril distribution at various depths of the corneal stroma of normal and CXL treated rats.

Corneal collagen cross-linking (CXL) is widely used to treat keratoconus and ecstatic corneal disorders. The present studies were carried out to investigate the distribution of glycosaminoglycans (GAGs) and collagen fibril (CF) at different depths of the normal and CXL treated corneal stroma of four week old rats 7 days after standard CXL application. Ten Wistar rats' corneas were used for the study. The epithelium of the cornea from the left eye of each rat was removed and treated with standard CXL application using riboflavin and Ultraviolet-A (UVA) (3 mW/cm2 for 30 min). The cornea from the right eye was used as the control cornea. The cornea was removed from the eye and processed for transmission electron microscopy. A bottom mounted Quemesa camera was used to capture digital images and these images were analysed using iTEM software. In the control cornea, the GAGs area size was not significantly different in the anterior, middle, and posterior stroma. In the CXL treated rats the GAGs area size gradually increased from the anterior to the posterior stroma whereas the spacing between the GAGs gradually decreased. There were very large GAGs present in the posterior stroma of the CXL treated rats. When comparing the control and CXL cornea, the GAGs area in the CXL cornea was significantly higher and inter-GAGs-spacing was smaller than in the control cornea. In the control cornea, the collagen fibrils diameter was higher in the anterior stroma and lowest in the posterior stroma. In the CXL treated cornea, the CF diameter and the interfibrillar spacing gradually decreased from the anterior to the posterior stroma. On comparison between the control and the CXL treated cornea, the interfibrillar spacing was significantly smaller in the CXL treated cornea than the control cornea in the anterior, middle, and posterior stroma but there was no difference in the diameter. The CXL treatment significantly increased the GAGs area and decreased the inter-GAGs-spacing, and inter-CF-spacing. This could be due to the gradual decline in the availability of riboflavin, UVA, and oxygen in the middle and posterior stroma. Further studies are required to investigate the role of keratan sulphate and chondroitin sulphate by using monoclonal antibodies with immunogold technique.

Collagen cross-linking beyond corneal ectasia: A comprehensive review.

The history of corneal cross-linking (CXL) dates back to 2003 when some German scientists investigated possible treatments to harden the corneal structure to increase its resistance in ectatic corneal diseases. Nowadays, CXL is considered the most effective therapy in ectatic corneal diseases due to its proven efficacy in hardening the cornea, thus halting the development of the disease. Since 2003, CXL applications have dramatically expanded and have been implemented in several other areas such as infectious keratitis, corneal edema, and before performing keratoplasty for various purposes. Moreover, several irradiation patterns are being studied to correct refractive errors, taking into account the corneal refractive changes that occur after the procedure. Currently, scleral cross-linking is also being investigated as a potential therapy in cases of progressive myopia and glaucoma. In this article, we provide a comprehensive overview of the available applications of cross-linking in nonectatic ocular conditions and highlight the possible future indications of this procedure.

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.

Comparison of long-term outcomes of simultaneous accelerated corneal crosslinking combined with intracorneal ring segment or topography-guided PRK.

PURPOSE: To compare long-term outcomes of simultaneous accelerated corneal crosslinking (CXL) with intrastromal corneal ring segments (CXL-ICRS) with simultaneous accelerated CXL with topography-guided photorefractive keratectomy (CXL-TG-PRK) in progressive keratoconus (KC). SETTING: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Prospective nonrandomized interventional study. METHODS: The change in visual and topographical outcomes of CXL-ICRS and CXL-TG-PRK 4 to 5 years postoperatively were compared using linear regression models adjusted for preoperative corrected distance visual acuity (CDVA) and maximum keratometry (Kmax). RESULTS: 57 eyes of 43 patients with progressive KC who underwent simultaneous accelerated (9 mW/cm 2 , 10 minutes) CXL-ICRS (n = 32) and CXL-TG-PRK (n = 25) were included. Mean follow-up duration was 51.28 (9.58) and 54.57 (5.81) months for the CXL-ICRS and CXL-TG-PRK groups, respectively. Initial mean Kmax was higher in the CXL-ICRS group compared with the CXL-TG-PRK group (60.68 ± 6.81 diopters [D] vs 57.15 ± 4.19 D, P = .02). At the last follow-up, change (improvement) in logMAR uncorrected distance visual acuity (UDVA) compared with that preoperatively was significant with CXL-ICRS (-0.31 ± 0.27, P < .001, which is equivalent to approximately 3 lines) and not significant with CXL-TG-PRK (-0.06 ± 0.42, P = .43). The logMAR CDVA improved significantly with CXL-ICRS (-0.22 ± 0.20, P < .001), but not with CXL-TG-PRK (-0.05 ± 0.22, P = .25). Adjusting for baseline Kmax and CDVA, the improvement in UDVA was significantly greater with CXL-ICRS than with CXL-TG-PRK (-0.27, 95% CI, 0.06-0.47, P = .01). Improvement in CDVA was not significantly different. CONCLUSIONS: In this cohort of progressive KC with long-term follow-up, UDVA showed more improvement with accelerated CXL-ICRS than with CXL-TG-PRK.