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Pharmacologic Alternatives to Riboflavin Photochemical Corneal Cross-Linking: A Comparison Study of Cell Toxicity Thresholds
摘要： PURPOSE. The efficacy of therapeutic cross-linking of the cornea using riboflavin photochemistry (commonly abbreviated as CXL) has caused its use to become widespread. Because there are known chemical agents that cross-link collagenous tissues, it may be possible to cross-link tissue pharmacologically. The present study was undertaken to compare the cell toxicity of such agents. METHODS. Nine topical cross-linking agents (five nitroalcohols, glyceraldehyde [GLYC], genipin [GP], paraformaldehyde [FA], and glutaraldehyde [GLUT]) were tested with four different cell lines (immortalized human corneal epithelial cells, human skin fibroblasts, primary bovine corneal endothelial cells, and immortalized human retinal pigment epithelial cells [ARPE-19]). The cells were grown in planar culture and exposed to each agent in a range of concentrations (0.001 mM to 10 mM) for 24 hours followed by a 48-hour recovery phase. Toxicity thresholds were determined by using the trypan blue exclusion method. RESULTS. A semiquantitative analysis using five categories of toxicity/fixation was carried out, based on plate attachment, uptake of trypan blue stain, and cellular fixation. The toxicity levels varied by a factor of 103 with the least toxic being mononitroalcohols and GLYC, intermediate toxicity for a nitrodiol and nitrotriol, and the most toxic being GLUT, FA, GP, and bronopol, a brominated nitrodiol. When comparing toxicity between different cell lines, the levels were generally in agreement. CONCLUSIONS. There are significant differences in cell toxicity among potential topical cross-linking compounds. The balance between cross-linking of tissue and cell toxicity should be borne in mind as compounds and strategies to improve mechanical tissue properties through therapeutic tissue cross-linking continue to develop.
关键词： protein cross-linking,cornea,cellular toxicity,keratoconus
更新于2025-09-23 15:23:52
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Determining the efficacy of corneal crosslinking in progressive keratoconus
摘要： Objective: To determine the Efficacy of Corneal Crosslinkage (CXL), using Corneal Topography, in eyes with progressive Keratoconus. Methods: This randomized control trial was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from October 2013 to April 2014. A total of 60 eyes of 30 patients were included who presented with bilateral progressive Keratoconus. Each eye of the patient was randomized either to a treatment group (Group-A) or control untreated group (GroupB) of 30 eyes each. A written informed consent was obtained from each patient, following which corneal crosslinkage (CXL) with topical riboflavin eye drops was performed. Follow up visit was done at three months post operatively, Corneal topography was repeated and recorded. Results: The mean age of the patients was 23.13±7.62 years (range 13 to 39 years). There were 26 males and 34 females patients. The mean simK value at the start of study was 50.94±4.84 diopters in Group-A and 49.73±5.24 diopters in Group-B. At three months follow-up, the mean simK value was significantly lower in Group-A (48.28±4.47) as compared to Group-B (51.11±4.85). Keratoconus improved/ remained stable in 34 (56.7%) eyes while progressive disease was noted in 26 (43.3%) eyes. When compared between the groups, the frequency of efficacy was significantly higher in Group-A (86.7% vs. 26.7%; p=.000) as compared to Group-B. Conclusion: Corneal Crosslinking was found effective in causing regression or halting the progression of disease in patients with progressive Keratoconus at three months follow-up , however, the efficacy of corneal crosslinking was unaffected by patient’s age and gender.
关键词： Corneal Crosslinking,Efficacy,Keratoconus
更新于2025-09-23 15:22:29
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Excimer laser treatment combined with riboflavin ultraviolet-A (UVA) collagen crosslinking (CXL) in keratoconus: a literature review
摘要： Purpose To review the clinical outcome of keratoconus patients after excimer laser treatment with combined riboflavin UV-A collagen crosslinking (CXL) treatment was reviewed in light of the UDVA, CDVA and HOA. Methods Following a PubMed-based literature review of studies on excimer laser treatment with combined riboflavin UV-A CXL published between 2009 and 2018, peer-reviewed English-written studies were evaluated using the GRADE approach (www.gradeworkinggroup.org). The current review focused on the change in the (un)corrected distance visual acuity (UDVA; CDVA) and higher-order aberrations (HOA) as well as the prevalence of postoperative complications. Results Five studies with a total of 573 eyes were included, thereby reporting on 479 eyes were treated with the aforementioned combination therapy. The control group consisted of 94 eyes in total. Changes between pre- and postoperative CDVA and/or UDVA were statistically significant in all five studies after at least a 24-month follow-up period for the combined excimer laser-assisted CXL treatment in comparison with the CXL-only treatment option. Three studies described statistically significant reduction in the number of total HOA, in particular, those related to coma and spherical aberration. Corneal haze was reported in four studies, but the condition was successfully treated in all cases. Conclusion Current studies suggest that CDVA, UDVA and HOA in low-to-moderate keratoconic patients improved in a combined treatment without sacrificing biomechanical stability of the cornea. However, long-term results are needed, as the studies in our review have a follow-up period of 68 months or less.
关键词： Refractive surgery,Keratoconus,Collagen-crosslinking,Photorefractive keratectomy
更新于2025-09-23 15:21:01
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Diurnal variation of anterior segment parameters handled with Scheimpflug imaging in keratoconus patients
摘要： Purpose To define diurnal changes in anterior segment parameters of keratoconus patients by using Scheimpflug imaging. Methods All keratoconus patients had corneal topography measurements 3 times a day (around 09:00 AM, 13:00 PM and 17:00 PM) by the same experienced operator. Three consecutive scans in each measurement session were obtained. The average of three measurements was used for analysis. A repeated measures analysis of variance with one within-subject factor (time of day) was carried out to assess diurnal variation. Results This study included 26 eyes of 26 patients with keratoconus. Significant diurnal variation was found in CCT and TCT measurements (P < 0.01, and P < 0.01, respectively). The mean amplitudes of change in CCT and TCT were 4.2 ± 1 μm (95% CI: 1.7–6.8 μm) and 4.1 ± 1.1 μm (95% CI: 1.2–8.0 μm), while the mean of CCT and TCT were 462.4 ± 34.5 μm (95% CI: 448.4–476.6 μm) and 452.9 ± 6.6 μm (95% CI: 439.3–466.5 μm), respectively. The maximum value and the lowest value were observed at 09:00 AM and at 17:00 PM, respectively. Other parameters except CCT and TCT did not show diurnal variation. Conclusion Statistically significant but clinically insignificant diurnal variation in CCT and TCT measurements of the keratoconus patients were detected over an 8-hour period (09:00 AM–17:00 PM).
关键词： Diurnal variation,Keratoconus,Anterior segment,Scheimpflug imaging
更新于2025-09-23 15:19:57
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Extrusion of Femtosecond Laser-Implanted Intrastromal Corneal Ring Segments in Keratoconic Eyes: Prevalence, Risk Factors, and Clinical Outcomes
摘要： Purpose. To evaluate the prevalence, possible risk factors, and clinical results of femtosecond laser implanted intrastromal corneal ring segment (ICRS) extrusion in keratoconic eyes. Patients and Methods. This is a retrospective observational study evaluating 333 eyes of 269 patients who were subjected to femtosecond laser-implanted Keraring ICRS in the Sohag Refractive Center, Sohag, Egypt, from January 2014 to January 2019. The study included eyes with channels created by a femtosecond laser (60 kHz IntraLase femtosecond system; Advanced Medical Optics, Santa Ana, California, USA) with implantation of Keraring intrastromal corneal ring segments (Mediphacos, Belo Horizonte, Brazil). Patient data and causes of Keraring extrusions were identi?ed as being those rings that migrated or showed melting of the cornea with no other reason which required segment removal. Results. Seven eyes were found to ?t the criteria of ring extrusion (2.1%) out of the 333 eyes which had Keraring implantation. All extruded rings were from patients with keratoconus grade 3, with eccentric cones, and with femtosecond creation of the tunnel. Four eyes belonging to 3 patients (57.1%) had a history of vernal Keratoconjunctivitis, yet they did not show signs of activity at the time of implantation. They reported excessive rubbing just before they presented with conjunctival hyperemia and foreign body sensation. Five eyes (71.4%) showed chronic sun exposure. The mean minimal corneal thickness was 401.85 μm (range 384–420 μm), while the mean maximum keratometry was 61 D (range 55.18–68.96 D). Most of the extruded rings had large arcs. Six eyes had crosslinking (CXL) at the same session of the Keraring implantation. The simultaneous CXL treatment is considered as a possible signi?cant risk factor for ring extrusion. Conclusion. ICRS is an e?ective reversible option for patients with keratoconus who are intolerant to hard contact lenses, yet the choice of cases and ring segments is mandatory for satisfactory results. Moreover, meticulous history taking and examination reduces the incidence of complications including extrusion.
关键词： clinical outcomes,risk factors,keratoconus,femtosecond laser,extrusion,intrastromal corneal ring segment
更新于2025-09-23 15:19:57
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Recent developments in keratoconus diagnosis
摘要： Introduction: Keratoconus and ectatic corneal diseases represent a hot area of research. The need to enhance diagnosis in order to recognize milder forms of the disease and identify inherent predisposition for ectasia progression has gained significant importance because of refractive surgery and also due to the development of new treatment modalities to treat ectatic corneal diseases. This article discusses the nomenclature related to the diagnostic tests used to characterize keratoconus and ectatic corneal diseases, providing a prospective discussion on the latest developments for the diagnosis and follow up of these conditions, including imaging modalities, biomechanical assessments, and an outlook in genetics and molecular biology. Areas covered: We performed an extensive Pubmed literature search, considering the latest developments in the diagnosis of keratoconus and additional ectatic corneal diseases. Expert Commentary: Corneal ectasia is characterized by biomechanical failure and stromal thinning, causing corneal bulging with subsequent visual impairment due to irregular astigmatism. Moderate and advanced stages are easily recognized, but the identification of mild or subclinical forms remains a challenge. Keratoconus is the most common ectatic corneal disease, being a bilateral, typically asymmetric and progressive corneal dystrophy. Corneal ectasia may occur unilaterally due to the impact from the environment, such as eye rubbing. The advent of refractive surgery and the development of new treatment modalities augmented the need for the diagnosis of milder forms of ectatic corneal disease and to document ectasia progression. Placido disc based corneal topography is sensitive to detect mild ectatic patterns in patients with relatively normal DCVA and biomicroscopy. However, the limitations of this technology are realized by the occurrence of post-refractive keratectasia despite normal anterior curvature maps and cases with suspicious topographic patterns that proceeded with LCV, based on advanced corneal imaging, resulting in documented stable outcomes. Corneal tomography, biomechanical assessment, and ocular wavefront analysis are among the diagnostic tools that enhance our ability to diagnose milder stages of keratoconus, or, even, to characterize ectasia susceptibility. Artificial intelligence and machine learning algorithms have been successful to integrate data and develop novel more accurate indices with enhanced sensitivity and specificity. This article discusses the latest developments in the diagnosis of keratoconus, including imaging modalities, biomechanical assessments, and an outlook in genetics and molecular biology.
关键词： ectasia,tomography,biomechanics,keratoconus,topography
更新于2025-09-23 15:19:57
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In vivo slit scanning confocal microscopic observation in a patient with moderate and severe keratoconus: a case report
摘要： A 22-year-old Indian female was referred to Sg Buloh hospital with the diagnosis of bilateral keratoconus. On examination, slit lamp biomicroscopy and corneal topography revealed stage 3 keratoconus in the right eye and stage 2 keratoconus in the left eye. Corneal cell morphology in both eyes was evaluated using confocal microscope. In qualitative observation, almost all corneal layers in right eye except endothelium were partially or completely obscured by haze. Additionally, morphological alterations, such as elongation of keratocyte nuclei and cluster of cells, and dark bands in the anterior stroma were observed in right eye. In the left eye, the amount of haze was less, allowing better visibility of the corneal layers compared with the right eye. The dark bands were evident in the posterior stroma. Quantitative analysis showed that anterior and posterior stromal keratocyte density and endothelium cell density were relatively low in the right eye (834.0, 700.5, and 2,133 cells/mm2, respectively) compared with the left eye (934.1, 750.6, and 2,361 cells/mm2, respectively). In this case, the right eye, exhibiting stage 3 keratoconus, showed more morphological alteration, particularly in the anterior stroma compared with the left eye with stage 2 keratoconus. Increased severity of the disease can explain these differences in corneal cell morphology.
关键词： confocal microscopy,keratocyte,stromal haze,striae,cornea,keratoconus
更新于2025-09-19 17:15:36
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Femtosecond laser–assisted intrastromal corneal lenticule implantation for treatment of advanced keratoconus in a child’s eye
摘要： We present a case of a 12-year-old male patient who received a femtosecond laser–assisted intrastromal implantation of a donor lenticule for the treatment of advanced keratoconus. Initially, the uncorrected distance visual acuity (UDVA) in the left eye was counting fingers (CF) and cycloplegic refraction was (cid:1)18.50 (cid:1)4.50 (cid:3) 85 Z 20/400. Preoperative corneal topography demonstrated a curvature of 65.90 (cid:3) 62/57.17 (cid:3) 152. Twelve months after lenticule implantation, the cornea was completely clear and the thickness changed from 245 mm to 639 mm. The UDVA was CF at 2 m and refraction was (cid:1)12.25 (cid:1)2.50 (cid:3) 180 Z 20/30, whereas topography demonstrated a curvature of 61.44 (cid:3) 52/59.28 (cid:3) 142. The results showed that the procedure was successful in thickening and flattening the cornea. It is expected that penetrating or deep anterior lamellar keratoplasty, if required, could be postponed to a more suitable age.
关键词： femtosecond laser,keratoconus,intrastromal corneal lenticule implantation,child
更新于2025-09-19 17:13:59
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Femtosecond Laser Implantation of a 355-Degree Intrastromal Corneal Ring Segment in Keratoconus: A Three-Year Follow-Up
摘要： Purpose. To evaluate the outcomes of femtosecond laser-assisted implantation of a 355-degree intracorneal ring (ICR) (Keraring) in patients with keratoconus in the three-year follow-up. Setting. Future Femtolaser Center, Sohag, Egypt. Design. Prospective interventional case series. Patients and Methods. A prospective case series of 38 eyes of 26 patients with keratoconus had implantation of the 355-degree ICR keraring after tunnel creation with a femtosecond laser. The uncorrected visual acuities (UCVA) and best-corrected visual acuities (BCVA), sphere, cylinder, and manifest refraction spherical equivalent (SE), and mean keratometry (K), K max, and K min were evaluated preoperatively and 3, 6, 12, 24, and 36 months postoperatively, and all complications were reported. Results. 38 eyes of 26 patients with mean age 25.92 ± 5.44 years were enrolled in the study, 11 were males (42.3%). The mean UCVA improved from 0.93 ± 0.21 to 0.63 ± 0.21 logMAR (P ≤ 0.001) and the mean BCVA from 0.67 ± 0.22 to 0.43 ± 0.26 logMAR (P < 0.001). The mean sphere, cylinder, and spherical equivalent have been changed dramatically from preoperative to 3 month postoperative, which is statistically signi?cant (P ≤ 0.001), and the changes between 1 and 2 years and 2 and 3 years are also considerable and statistically signi?cant; the K max and K min and K mean improved and the changes were statistically signi?cant (P ≤ 0.001), and the changes between one, two, and three years were also statistically signi?cant. The safety and e?cacy indices were changed through the three-year follow-up. The complications were corneal neovascularization (36.84%), corneal melting (26.3%), and ring extrusion (31.5%) at the end of the study. Conclusions. Implantation of a 355-degree intracorneal keraring using femtosecond laser improved the visual, refractive, and topographic parameters in keratoconus patients, with a high rate of ICR extrusion and instability. The study has been registered for the Pan African Clinical Trial Registry (http://www.pactr.org) database within No: PACTR201810796878908 on 29 October 2018.
关键词： keratoconus,Keraring,refractive error,femtosecond laser,visual acuity,corneal topography,intracorneal ring
更新于2025-09-12 10:27:22
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Comparison of clinical outcomes between manual and femtosecond laser techniques for intrastromal corneal ring segment implantation
摘要： The purpose was to compare the visual, refractive and aberrometric results of intrastromal corneal ring segments implantation with manual dissection and femtosecond laser–assisted surgery. This is a multicentre study, which included consecutive patients with paracentral keratoconus, in which the difference between the axes of the topographic flattest and the coma aberration was <60°, who had Ferrara-type intrastromal corneal ring segment implantation using manual dissection or femtosecond laser technique. LogMAR uncorrected (uncorrected distance visual acuity) and corrected (corrected distance visual acuity) distance visual acuity, refractive errors and the root mean square for corneal coma-like aberration were recorded before and at 6 months after surgery. The study included 84 and 110 eyes in the manual group and in the femtosecond group, respectively. After surgery, there was a statistically significant improvement in uncorrected distance visual acuity and corrected distance visual acuity for both groups (p < 0.0001), and there were no statistically significant differences between groups (p > 0.3). For both groups, there was a reduction in spherical equivalent after intrastromal corneal ring segment implantation (p < 0.0001). There were no statistically significant differences between groups in the magnitude of spherical equivalent reduction (p = 0.34) The magnitude of the root mean square coma-like reduction was 0.93 ± 0.76 and 0.83 ± 0.80 μm in the manual and femtosecond group, respectively (p = 0.2). While in the femtosecond laser group no complications were reported, in the manual group, the intraoperative or postoperative complications rate was 13.09%. Although both surgical techniques provide comparable visual, refractive and aberrometric outcomes, it should be noted that the femtosecond laser is a safer surgical procedure, with no complications reported.
关键词： intracorneal ring segments,femtosecond laser surgery,manual surgery,Keratoconus
更新于2025-09-11 14:15:04