Transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus.

BACKGROUND: Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or paracentral cornea, irregular corneal scarring, or corneal perforation. Disease onset usually occurs in the second to fourth decade of life, periods of peak educational attainment or career development. The condition is lifelong and sight-threatening. Corneal collagen crosslinking (CXL) using ultraviolet A (UVA) light applied to the cornea is the only treatment that has been shown to slow progression of disease. The original, more widely known technique involves application of UVA light to de-epithelialized cornea, to which a photosensitizer (riboflavin) is added topically throughout the irradiation process. Transepithelial CXL is a recently advocated alternative to the standard CXL procedure, in that the epithelium is kept intact during CXL. Retention of the epithelium offers the putative advantages of faster healing, less patient discomfort, faster visual rehabilitation, and less risk of corneal haze. OBJECTIVES: To assess the short- and long-term effectiveness and safety of transepithelial CXL compared with epithelium-off CXL for progressive keratoconus. SEARCH METHODS: To identify potentially eligible studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature database (LILACS); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not impose any date or language restrictions. We last searched the electronic databases on 15 January 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which transepithelial CXL had been compared with epithelium-off CXL in participants with progressive keratoconus. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 13 studies with 723 eyes of 578 participants enrolled; 13 to 119 participants were enrolled per study. Seven studies were conducted in Europe, three in the Middle East, and one each in India, Russia, and Turkey. Seven studies were parallel-group RCTs, one study was an RCT with a paired-eyes design, and five studies were RCTs in which both eyes of some or all participants were assigned to the same intervention. Eleven studies compared transepithelial CXL with epithelium-off CXL in participants with progressive keratoconus. There was no evidence of an important difference between intervention groups in maximum keratometry (denoted 'maximum K' or 'Kmax'; also known as steepest keratometry measurement) at 12 months or later (mean difference (MD) 0.99 diopters (D), 95% CI -0.11 to 2.09; 5 studies; 177 eyes; I2 = 41%; very low certainty evidence). Few studies described other outcomes of interest. The evidence is very uncertain that epithelium-off CXL may have a small (data from two studies were not pooled due to considerable heterogeneity (I2 = 92%)) or no effect on stabilization of progressive keratoconus compared with transepithelial CXL; comparison of the estimated proportions of eyes with decreases or increases of 2 or more diopters in maximum K at 12 months from one study with 61 eyes was RR 0.32 (95% CI 0.09 to 1.12) and RR (non-event) 0.86 (95% CI 0.74 to 1.00), respectively (very low certainty). We did not estimate an overall effect on corrected-distance visual acuity (CDVA) because substantial heterogeneity was detected (I2 = 70%). No study evaluated CDVA gain or loss of 10 or more letters on a logarithm of the minimum angle of resolution (logMAR) chart. Transepithelial CXL may result in little to no difference in CDVA at 12 months or beyond. Four studies reported that either no adverse events or no serious adverse events had been observed. Another study noted no change in endothelial cell count after either procedure. Moderate certainty evidence from 4 studies (221 eyes) found that epithelium-off CXL resulted in a slight increase in corneal haze or scarring when compared to transepithelial CXL (RR (non-event) 1.07, 95% CI 1.01 to 1.14). Three studies, one of which had three arms, compared outcomes among participants assigned to transepithelial CXL using iontophoresis versus those assigned to epithelium-off CXL. No conclusive evidence was found for either keratometry or visual acuity outcomes at 12 months or later after surgery. Low certainty evidence suggests that transepithelial CXL using iontophoresis results in no difference in logMAR CDVA (MD 0.00 letter, 95% CI -0.04 to 0.04; 2 studies; 51 eyes). Only one study examined gain or loss of 10 or more logMAR letters. In terms of adverse events, one case of subepithelial infiltrate was reported after transepithelial CXL with iontophoresis, whereas two cases of faint corneal scars and four cases of permanent haze were observed after epithelium-off CXL. Vogt's striae were found in one eye after each intervention. The certainty of the evidence was low or very low for the outcomes in this comparison due to imprecision of estimates for all outcomes and risk of bias in the studies from which data have been reported. AUTHORS' CONCLUSIONS: Because of lack of precision, frequent indeterminate risk of bias due to inadequate reporting, and inconsistency in outcomes measured and reported among studies in this systematic review, it remains unknown whether transepithelial CXL, or any other approach, may confer an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to further progression of keratoconus, visual acuity outcomes, and patient-reported outcomes (PROs). Arrest of the progression of keratoconus should be the primary outcome of interest in future trials of CXL, particularly when comparing the effectiveness of different approaches to CXL. Furthermore, methods of assessing and defining progressive keratoconus should be standardized. Trials with longer follow-up are required in order to assure that outcomes are measured after corneal wound-healing and stabilization of keratoconus. In addition, perioperative, intraoperative, and postoperative care should be standardized to permit meaningful comparisons of CXL methods. Methods to increase penetration of riboflavin through intact epithelium as well as delivery of increased dose of UVA may be needed to improve outcomes. PROs should be measured and reported. The visual significance of adverse outcomes, such as corneal haze, should be assessed and correlated with other outcomes, including PROs.

Pachymetry and Elevation Back Map Changes in Keratoconus Patients After Crosslinking Procedure.

INTRODUCTION: The crosslinking (CXL) procedure using the standard Dresden protocol is established as the gold standard for the treatment of progressive keratoconus. AIM: The aim of this paper is to correlate the pachymetry and elevation back map (EBM) changes in the period from 3 to12 months of keratoconus patients after the CXL procedure. M. METHODS: Forty-four eyes of 34 patients with keratoconus were analyzed after performed standard Dresden protocol CXL procedure. All of them underwent complete preoperative examination with a follow up of 12 months with a focus on pachymetry and EBM changes performed by Oculus Pentacam (Scheimpflug technology) analysis. RESULTS: Pachymetry changed significantly in 12 months post cross-linking, especially in the first 6 months after which it slightly increased. Differences in EBM preoperatively and 12 months postoperatively were not statistically significant. CONCLUSION: Corneal pachymetry in keratoconus patients decreases after the CXL procedure. Differences in pachymetry preoperatively and 3, 6 and 12 months postoperatively were statistically significant, but the value of corneal thickness increased from the third month to 12 months post-op. Differences in EBM preoperatively and 12 months postoperatively were not still statistically significant, which is good, because the increase in elevation, as one of the signs of progression of the keratoconus - did not occur.

Is there a potential link between keratoconus and autism spectrum disorders?: A case report and literature review.

RATIONALE: Eye rubbing (ER) is a proven factor that can trigger the onset and progression of keratoconus (KC). Apart from allergy, ER is a repetitive motor stereotypy. Eye rubbing is frequently observed in children with autism spectrum disorders (ASDs) and in individuals who may be at risk for developing KC. We present a child with ASD who developed progressive KC following standard corneal cross-linking (CXL), most likely because of abnormal ER associated with allergy and repetitive behavior due to ASD symptoms. PATIENT CONCERNS: A 14-year-old boy was referred to our clinic because of asymmetric visual acuity reduction. DIAGNOSIS: The child was diagnosed as having keratoconus. He had a strong ER habit. The child had been previously diagnosed as having ASD. INTERVENTIONS: Corneal cross-linking was performed in both the eyes. On account of keratoconus progression, most likely associated with persistent ER habit, he was retreated with CXL in the right eye. Behavioral modification intervention for ER habit reversal was also applied. OUTCOMES: Corneal cross-linking in combination with behavioral modification intervention for ER habit reversal prevented further KC progression. LESSONS: Behavioral interventions are likely to provide positive results in an ER habit reversal in children with ASD. Keratoconus treatment with CXL combined with behavioral management for ER reversal seemed effective in halting keratoconus progression in a young patient with ASD.

Baseline factors predicting the need for corneal crosslinking in patients with keratoconus.

INTRODUCTION: The primary purpose of crosslinking is to halt the progression of ectasia. We retrospectively assessed the condition of keratoconus patients who were followed-up at least twice after the initial examination to evaluate keratoconus progression, to identify definitive factors to predict a later need for corneal crosslinking (CXL). METHODS: The medical charts of 158 eyes of 158 keratoconus patients (112 males and 46 females; mean age, 27.8 ± 11.7 years), who were followed up at the Department of Ophthalmology, Keio University School of Medicine at least twice after the initial examination to evaluate keratoconus progression were retrospectively reviewed. Best-spectacle corrected visual acuity, intraocular pressure, steepest corneal axis on the anterior float (Ks), thinnest corneal thickness according to Pentacam® HR, and corneal endothelial cell density were assessed. Gender, age, onset age of keratoconus, history of atopic dermatitis, and Pentacam® indices were also recorded. CXL was performed when the eye showed significant keratoconus progression, an increase in the steepest keratometric value, or an increase in the spherical equivalent or cylinder power of the manifest refraction by more than 1.0 D versus the respective values 2 years prior. Predictor variables and the requirement for CXL were analyzed using logistic regression. RESULTS: Fifty-eight eyes required CXL treatment. The best predictor of the requirement for CXL was patient age, followed by the Pentacam® Rmin (the minimum sagittal curvature evaluated by Pentacam®) value. The incidence of CXL was 86.4% in the < 20 years age group, with an Rmin of ≤ 5.73 mm, whereas 10.8% in the ≥ 27 years age group with an Rmin > 5.73 mm underwent treatment. CONCLUSIONS: An age of < 20 years and an Rmin value of ≤ 5.73 mm predicted keratoconus progression and the requirement for CXL treatment in the near future.

[Complications and postoperative therapeutic strategies in cross-linking]. / Komplikationen und postoperative Therapiestrategien beim Crosslinking.

CLINICAL ISSUE: The reduced corneal mechanical stability in keratoconus and similar collagen diseases can lead to a progressive and irregular corneal shape and decrease of visual acuity. DIAGNOSTICS: A progression of keratectatic diseases can be shown with corneal topography. TREATMENT: Keratoconus can be treated by photo-oxidative cross-linking of the corneal collagen. In order to achieve a high absorption of irradiation energy in the cornea, riboflavin at a concentration of 0.1% and UVA light at a wavelength of 370 nm corresponding to the relative maximum absorption of riboflavin (vitamin B2) are used. Evidence for corneal cross-linking are the increase of biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibers. The currently available data demonstrate that the therapeutic cross-linking procedure is safe when respecting the important theoretical and clinical parameters and that a progression of the keratoconus can be avoided. In 80% of cases an average levelling of the curvature of approximately 2 dpt can be achieved, which leads not only to stabilization but also to an increase in visual acuity of approximately 1.2 lines. ASSESSMENT: In a Cochrane review from 2015 publications about complications and results were reviewed. Complication rates ranged from 1-10% depending on the initial situation, comorbidities and stage of the keratoconus. The most important complications are early epithelial wound healing problems as well as extremely rare perforations. PRACTICAL RECOMMENDATIONS: Corneal cross-linking is a well-established and safe procedure but is not free of complications.

[Predictive factors for visual outcome after corneal collagen crosslinking treatment in progressive keratoconus: One-year refractive and topographic results]. / Facteurs prédictifs de bonne réponse au crosslinking d'un kératocône évolutif : résultats réfractifs et topographiques à un an postopératoire.

PURPOSE: To assess the effects of preoperative patient characteristics on clinical outcomes of corneal collagen crosslinking (CXL) in patients with progressive keratoconus. PATIENTS AND METHODS: Fifty-four eyes of 41 patients underwent CXL for progressive keratoconus between June 2011 and December 2012. Corneal topography (Orbscan(®)) was assessed at 1, 3, and 6 months and 1 year after CXL treatment and compared with preoperative data. RESULTS: A significant improvement in 1-year postoperative best-corrected visual acuity (BCVA) (0.16±0.21 LogMar preoperatively versus 0.09±0.16 LogMar postoperatively, P=0.007) and in 3mm topographic central irregular astigmatism (P=0.04) was demonstrated with CXL. No significant change was noted for refractive astigmatism (P=0.69), or for 1-year postoperative Kmax (48.4 D±4.1 at baseline versus 48.5 D±4.1 postoperatively, P=0.46). Predictive factors for BVCA improvement were low preoperative BCVA, high refractive astigmatism and advanced keratoconus. Predictive factors for stability of postoperative Kmax values were early keratoconus, and central cone ("nipple" morphology of the cone mainly located in the central 3mm of the cornea). CONCLUSION: This retrospective study confirms the efficacy of CXL for progressive keratoconus, from a refractive as well as topographic standpoint. While cone localization or its eccentricity seems to explain the variability of CXL efficacy reported in the literature, cone severity appears to be the main predictive factor for a lack of topographic stability after CXL treatment but must be weighted by the preferential localization of the cone (3 or 5mm central corneal zone).

Understanding of the viscoelastic response of the human corneal stroma induced by riboflavin/UV-a cross-linking at the nano level.

PURPOSE: To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. METHODS: Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young's modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. RESULTS: The Young's modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). CONCLUSIONS: The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions.

Variación de la elevación anterior y posterior de la córnea tras el crosslinking corneal / Changes in the anterior and posterior elevation of the cornea after the corneal crosslinking

OBJETIVO: determinar las variaciones de la elevación anterior y posterior de la córnea con el tratamiento de crosslinking corneal en pacientes con queratocono en el Servicio de Córnea del Instituto Cubano de Oftalmología "Ramón Pando Ferrer". MÉTODOs: se realizó un estudio descriptivo, retrospectivo, a 30 ojos de 30 pacientes con queratocono a los cuales se les realizó el crosslinking corneal. Se recogieron los datos en el preoperatorio a los 6, 12 y 24 meses. Las variables estudiadas fueron: esfera mejor ajustada anterior, elevación anterior, esfera mejor ajustada posterior y elevación posterior. RESULTADOS: la esfera mejor ajustada anterior en el preoperatorio de 7,34 mm permaneció sin diferencia significativa en el posoperatorio y la elevación anterior mostró una reducción estadísticamente significativa de 20,73 µm en el preoperatorio a 14,90 µm al año y 15,93 µm a los 2 años. La esfera de mejor ajuste posterior de 5,94 mm no sufrió modificaciones en el posoperatorio, ni la elevación posterior media de 31,80 µm. CONCLUSIONES: después del crosslinking corneal la elevación anterior disminuye y la posterior se mantiene igual.

OBJECTIVE: to determine the anterior and posterior corneal surface elevation in the corneal crosslinking surgical treatment applied to patients with keratoconus at the corneal service of "Ramón Pando Ferrer" Cuban Institute of Ophthalmology. METHODS: a retrospective and descriptive study of 30 eyes from 30 patients with progressive keratoconus who underwent the corneal collagen crosslinking. Data were collected preoperatively at 6, 12 and 24 months. The studied variables were best fit anterior sphere, anterior elevation, best posterior fit sphere and posterior corneal elevation. RESULTS: the preoperative best fit anterior sphere was 7,34 mm and there was no difference in the postoperative period. The anterior corneal surface elevation showed statistically significant reduction from 20,73 µm in the preoperative period to 14,90 µm in the first year and 15,93 µm in the second year after surgery. There was no changes either in the posterior best fit sphere of 5,94 mm or in the posterior elevation of 31,80 µm. CONCLUSIONS: after the corneal crosslinking, there is a reduction of the anterior elevation and the posterior elevation remains the same.

Variación de la elevación anterior y posterior de la córnea tras el crosslinking corneal / Changes in the anterior and posterior elevation of the cornea after the corneal crosslinking

Objetivo: determinar las variaciones de la elevación anterior y posterior de la córnea con el tratamiento de crosslinking corneal en pacientes con queratocono en el Servicio de Córnea del Instituto Cubano de Oftalmología Ramón Pando Ferrer. Métodos: se realizó un estudio descriptivo, retrospectivo, a 30 ojos de 30 pacientes con queratocono a los cuales se les realizó el crosslinking corneal. Se recogieron los datos en el preoperatorio a los 6, 12 y 24 meses. Las variables estudiadas fueron: esfera mejor ajustada anterior, elevación anterior, esfera mejor ajustada posterior y elevación posterior. Resultados: la esfera mejor ajustada anterior en el preoperatorio de 7,34 mm permaneció sin diferencia significativa en el posoperatorio y la elevación anterior mostró una reducción estadísticamente significativa de 20,73 µm en el preoperatorio a 14,90 µm al año y 15,93 µm a los 2 años. La esfera de mejor ajuste posterior de 5,94 mm no sufrió modificaciones en el posoperatorio, ni la elevación posterior media de 31,80 µm.Conclusiones: después del crosslinking corneal la elevación anterior disminuye y la posterior se mantiene igual(AU)

Objective: to determine the anterior and posterior corneal surface elevation in the corneal crosslinking surgical treatment applied to patients with keratoconus at the corneal service of Ramón Pando Ferrer Cuban Institute of Ophthalmology. Methods: a retrospective and descriptive study of 30 eyes from 30 patients with progressive keratoconus who underwent the corneal collagen crosslinking. Data were collected preoperatively at 6, 12 and 24 months. The studied variables were best fit anterior sphere, anterior elevation, best posterior fit sphere and posterior corneal elevation. Results: the preoperative best fit anterior sphere was 7,34 mm and there was no difference in the postoperative period. The anterior corneal surface elevation showed statistically significant reduction from 20,73 µm in the preoperative period to 14,90 µm in the first year and 15,93 µm in the second year after surgery. There was no changes either in the posterior best fit sphere of 5,94 mm or in the posterior elevation of 31,80 µm.Conclusions: after the corneal crosslinking, there is a reduction of the anterior elevation and the posterior elevation remains the same(AU)

An overview of corneal collagen cross-linking (CXL).

Corneal collagen cross-linking (CXL) was first described over a decade ago and is now considered to be one of the most important surgical innovations of modern ophthalmology. Prior to its introduction, no interventions were available to arrest, or slow down ectatic disease progression, with corneal transplantation required in the majority of cases. Unlike earlier treatments of corneal ectasias that attempted to only improve the consequences of the disease, CXL aims to address the corneal biomechanical weakening itself. The long-term safety and efficacy of CXL have been established in several studies that have documented significant improvements in all outcome measures (visual acuity, spherical equivalent, astigmatism, and keratometric findings). The emerging combination of CXL with other interventions (termed 'CXL plus') optimizes the visual and topographic outcomes. This, along with the expansion of the techniques' indications for other clinical conditions, such as microbial keratitis, highlights the continuous improvement of the initial technique and confirms its wide acceptance. Overall, CXL has already demonstrated much promise and has several clinical indications, representing a clear example of recent advances in ocular therapy.

The results of corneal cross-linking in the treatment of keratoconus.

GOAL: To estimate corneal cross-linking (CXL) in keratoconus not only as a treatment to heal and increase the corneal stability then to consider it as a refractive procedure. METHODS: 28 eyes of 22 patients with progressive keratokonus were enrolled in prospective comparative study. Average follow up was 9 +/- 2 months (range 5 to 12 months). RESULTS: 6 months later uncorrected visual acuity (UCVA) was 0,2 (range 0,1 -0,5) and was significant higher to UCVA one month after the operation but not different to the results of UCVA before the CXL and three months later. The visual acuity with spectacles or hard contact lenses (BCVA) 6 months after CXL was 0,8 (range 0,57 -1,0) and was extremely higher then before the intervention (p=0,003), one month after CXL (p= 0,001) and significantly higher three months later (p=0,011). CONCLUSION: the CXL shows evident reduction in spherical equivalent refraction, cylinder and max K.

Structural response of human corneal and scleral tissues to collagen cross-linking treatment with riboflavin and ultraviolet A light.

High success rates in clinical trials on keratoconic corneas suggest the possibility of efficient treatment against myopic progression. This study quantitatively investigated the in vitro ultrastructural effects of a photooxidative collagen cross-linking treatment with photosensitizer riboflavin and UVA light in human corneo-scleral collagen fibrils. A total of 30.8 × 2 mm corneo-scleral strips from donor tissue were sagittally dissected using a scalpel. The five analytic parameters namely fibril density, fibril area, corneo-scleral thickness, fibril diameter, and fibril arrangement were investigated before and after riboflavin-UVA-catalyzed collagen cross-linking treatment. Collagen cross-linking effects were measured at the corneo-scleral stroma and were based on clinical corneal cross-linking procedures. The structural response levels were assessed by histology, digital mechanical caliper measurement, scanning electron microscopy, and atomic force microscopy. Riboflavin-UVA-catalyzed collagen cross-linking treatment led to an increase in the area, density, and diameters of both corneal (110, 112, and 103 %) and scleral (133, 133, and 127 %) stromal collagens. It also led to increases in corneal (107 %) and scleral (105 %) thickness. Collagen cross-linking treatment through riboflavin-sensitized photoreaction may cause structural property changes in the collagen fibril network of the cornea and sclera due to stromal edema and interfibrillar spacing narrowing. These changes were particularly prominent in the sclera. This technique can be used to treat progressive keratoconus in the cornea as well as progressive myopia in the sclera. Long-term collagen cross-linking treatment of keratoconic and myopic progression dramatically improves weakened corneo-scleral tissues.

Efectividad del crosslinking del colágeno corneal en el tratamiento del queratocono / Effectiveness of the corneal collagen crosslinking in the treatment of keratoconus

Objetivo: determinar la efectividad del tratamiento de crosslinking del colágeno corneal en pacientes con queratocono progresivo en el Instituto Cubano de Oftalmología Ramón Pando Ferrer.Métodos: estudio descriptivo, retrospectivo, en 30 pacientes (30 ojos) con queratocono progresivo que se les realizó el crosslinking del colágeno corneal. Se recogieron los datos en el preoperatorio, al mes, 3 meses, 6 meses y al año. Las variables estudiadas fueron: edad, sexo, estadio del queratocono, mejor agudeza visual corregida, equivalente esférico, queratometría máxima topográfica, algunos índices topográficos de diagnóstico de queratocono, el coma y la paquimetría óptica...

Objective: to determine the effectiveness of corneal collagen crosslinking in patients with progressive keratoconus performed at Ramón Pando Ferrer Cuban Institute of Ophthalmology.Methods: a retrospective and descriptive study was performed in 30 patients (30 eyes) with progressive keratoconus, who underwent the corneal collagen crosslinking. Data were collected preoperatively on one month, 3 months, 6 months and one year. The studied variables were age, sex, stage of keratoconus, best corrected visual acuity, spherical equivalent, maximum topographic keratometry, some topographic indexes of keratoconus diagnosis, coma and optical pachymetry...

Efectividad del crosslinking del colágeno corneal en el tratamiento del queratocono / Effectiveness of the corneal collagen crosslinking in the treatment of keratoconus

Objetivo: determinar la efectividad del tratamiento de crosslinking del colágeno corneal en pacientes con queratocono progresivo en el Instituto Cubano de Oftalmología Ramón Pando Ferrer.Métodos: estudio descriptivo, retrospectivo, en 30 pacientes (30 ojos) con queratocono progresivo que se les realizó el crosslinking del colágeno corneal. Se recogieron los datos en el preoperatorio, al mes, 3 meses, 6 meses y al año. Las variables estudiadas fueron: edad, sexo, estadio del queratocono, mejor agudeza visual corregida, equivalente esférico, queratometría máxima topográfica, algunos índices topográficos de diagnóstico de queratocono, el coma y la paquimetría óptica...

Objective: to determine the effectiveness of corneal collagen crosslinking in patients with progressive keratoconus performed at Ramón Pando Ferrer Cuban Institute of Ophthalmology.Methods: a retrospective and descriptive study was performed in 30 patients (30 eyes) with progressive keratoconus, who underwent the corneal collagen crosslinking. Data were collected preoperatively on one month, 3 months, 6 months and one year. The studied variables were age, sex, stage of keratoconus, best corrected visual acuity, spherical equivalent, maximum topographic keratometry, some topographic indexes of keratoconus diagnosis, coma and optical pachymetry...

Potential apoptotic effect of ultraviolet-A irradiation during cross-linking: a study on ex vivo cultivated limbal epithelial cells.

AIM/BACKGROUND: To study the effects of ultraviolet-A (UV-A) irradiation, in the presence or absence of riboflavin, on ex vivo cultured limbal epithelial cells (LECs). METHODS: The study was carried out in a super specialty ophthalmic hospital. Ex vivo cultured LECs were grown on denuded amniotic membranes and exposed to similar levels of UV-A radiation used during corneal cross-linking (CXL), in the presence or absence of the photosensitiser, riboflavin. These cells were then used for extraction of RNA, cDNA conversion, and antibody staining. Quantitative PCR and immunofluorescence staining were performed to evaluate the apoptotic state of treated and non-treated LECs. Statistical analyses were evaluated using a Student's t test. RESULTS: We found that bcl-2, an antiapoptotic gene, was downregulated, whereas, bax, a proapoptotic gene, was upregulated. After LECs were exposed to UV-A radiation, a significant upregulation of both caspase 3 and caspase 9 was observed in treated cells when compared with untreated LECs. CONCLUSIONS: These results indicate that exposure of LECs to UV-A dosages similar to those used in the CXL procedure promotes the expression of genes known to promote apoptosis. In the presence of riboflavin, the damage caused by UV-A treatment was marginalised, but not totally blocked.

Refractive, topographic, and visual outcomes of same-day corneal cross-linking with Ferrara intracorneal ring segments in patients with progressive keratoconus.

PURPOSE: To report refractive, topographic, and visual outcomes 12 months after same-day treatment with corneal cross-linking (CXL) and Ferrara intracorneal ring segments (ICRS) in eyes with progressive keratoconus (KC) and contact lens intolerance. METHODS: This was a case series of 7 eyes (7 patients) with progressive mild to moderate keratoconus and contact lens intolerance undergoing implantation of Ferrara ICRS immediately followed by corneal cross-linking. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refractive error, pachymetry, and keratometry were evaluated at 3, 6, and 12 months of follow-up. RESULTS: Mean follow-up was 11.7 ± 3.6 months (range, 5-17 months). Mean preoperative UCVA and BSCVA were 0.10 ± 0.07 (range, 0.05-0.2) and 0.56 ± 0.08 (range, 0.5-0.7), respectively. One year after the treatment, mean UCVA and BSCVA measured 0.60 ± 0.24 (range, 0.32-0.9) and 0.82 ± 0.25 (range, 0.5-1.2), respectively. The mean spherical equivalent decreased significantly (P < 0.05) with 3.5 diopters (D). Mean K values (average keratometry of the cornea) decreased from 46.81 ± 2.13 D (range, 44-51 D) to 43.97 ± 2.22 D (range, 42-47.5 D) 1 year after the treatment. The average preoperative thinnest pachymetry measured 462 ± 46 µm (range, 410 ± 546 µm) and did not change significantly after the treatment. In patient 1, the inferior ICRS was removed 5 months postoperatively because of implant migration. CONCLUSIONS: The combined treatment of corneal cross-linking and Ferrara ICRS is a safe procedure that may be considered in patients with progressive mild to moderate KC and contact lens intolerance.

Ultra B2 - Promoção de ligações covalentes do colágeno corneal (Corneal cross-linking) no tratamento de ceratocone: resultados preliminares / Corneal Cross-linking for the treatment of keratoconus: preliminary results

OBJETIVO: Apresentar os resultados visuais e ceratométricos, seis meses após tratamento foto-terapêutico com luz ultravioleta (UV) e vitamina B2 (Ultra B2), em pacientes com ceratocone progressivo. MÉTODOS: Vinte e cinco olhos de 20 pacientes (15 homens e 5 mulheres) com ceratocone progressivo, determinado pelo aumento de curvatura em exames seriados de topografia corneal, nos últimos seis meses foram avaliados. Acuidade visual não corrigida (UVA), acuidade visual melhor corrigida com óculos (BSCVA), equivalente esférico (SEQ), cilindro refrativo manifesto e a curvatura máxima (max K) pré e pós-operatórios (1, 3 e 6 meses) foram determinadas. Todos os pacientes foram submetidos ao tratamento Ultra B2 usando riboflavina (vitamina B2) e a luz ultravioleta (UV, 370 nm). O epitélio corneal foi removido após assepsia, colocação de blefarostato e anestesia tópica com proparacaína, por meio de solução de álcool hidratado (20 por cento) utilizada por 30 segundos. A córnea foi saturada com vitamina B2 por 15 minutos; em seguida, foi irradiada por luz UV por 30 minutos. Ao final do procedimento, foi colocada lente de contato terapêutica (LCT), mantida até a epitelização total. RESULTADOS: Houve melhora na UVA após o primeiro mês (de 0,15 ± 0,15 para 0,23 ± 0,20), com contínua mudança no terceiro e sexto mês pós-operatório, atingindo a diferença estatisticamente significante nesse período (p=0,025 e p=0,037 respectivamente). BSCVA melhorou de 0,41 ± 0,27 para 0,49 ± 0,29 no sexto mês, sem atingir a diferença estatisticamente significante. A progressão do ceratocone após o procedimento não foi notada em nenhum paciente, em comparação com o avanço topográfico nos 6 meses precedentes. Após 6 meses do procedimento, max K diminuiu em mais que 2,00 D (de 53,02 ± 8,42 para 50,88 ± 6,05 D), SEQ em menos que 1 D (de -3,27 ± 4,08 para -2,68 ± 3,02 D) e o cilindro refrativo em menos que 0,5 D (de -2,29 ± 1,77 para -1,86 ± 0,92), sem atingir diferença estatisticamente...

PURPOSE: To present early visual and keratometric results for corneal cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus. METHODS: Twenty-five eyes of twenty patients (15 males and 5 females) with a progressive keratoconus in the previous 6 months were followed. Unaided visual acuity (UVA), best spectacle corrected visual acuity (BSCVA), spherical equivalent (SEQ), manifest cylinder, and maximal corneal curvature (max K) values were followed at 1, 3 and 6 months. All patients were submitted to corneal cross-linking using riboflavin (vitamin B2) as the photosensitizer and ultraviolet light (UV, wavelength 370 nm). Epithelium was removed with 20 percent alcohol, cornea was soaked with vitamin B2 for 15 min, and then irradiated with UV light for 30 min, after which a bandage contact lens (BCL) was placed. RESULTS: UVA increased after one month (from 0.15 ± 0.15 to 0.23 ± 0.20), and went on increasing at 3 and 6 months, reaching statistical significance (p=0.025 e p=0.037, respectively). BSCVA increased from 0.41 ± 0.27 to 0.49 ± 0.29 at month six, without reaching statistical significance at any time point. Progression of keratoconus stopped in all patients, in contrast with progression in all of them in the six-month period prior to the surgery. Max K decreased by more than 2 D (from 53.02 ± 8.42 to 50.88 ± 6.05 D), SEQ less that 1 D (from -3.27 ± 4.08 to -2.68 ± 3.02 D), while refractive cylinder decreased less than 0.5 D (from -2.29 ± 1.77 to -1.86 ± 0.92 D), without reaching a statistically significant difference. None of the eyes lost any line of BSCVA, 12 maintained the preoperative BSCVA, 7 gained one line, 5 gained two lines, and 1 patient gained three lines of BSCVA. CONCLUSIONS: Corneal cross-linking with riboflavin and UV light seems to be a safe (no loss of BSCVA) and effective (anatomical and optical properties maintained) procedure, which has shown to stop the progression of the keratoconus...

[Collagen crosslinking with riboflavin and UVA-light in keratoconus]. / Kollagen-Crosslinking mit Riboflavin und UVA-Licht beim Keratokonus.

Reduced corneal mechanical stability in keratoconus and similar corneal diseases can be treated by photooxidative crosslinking of the corneal collagen. This method is currently undergoing clinical evaluation worldwide. To achieve high absorption of the irradiation energy in the cornea, riboflavin at a concentration of 0.1% and UVA light at a wavelength of 370 nm corresponding to the relative maximum of absorption of riboflavin (vitamin B2) is used. These therapeutic parameters were experimentally tested and have been proven clinically. Current data demonstrate that the therapeutic crosslinking procedure is safe when the important theoretical and clinical parameters are observed, and that progression of keratoconus can be prevented. In all, 80% of the published cases show a decrease in corneal curvature of about 2 D, which leads not only to stabilisation but also to an increase in visual acuity.

[Biophysical principles of collagen cross-linking]. / Biophysikalische Grundlagen der Kollagenvernetzung.

BACKGROUND: The reduced mechanical stability of the cornea in keratoconus or in keratectasia after Lasik may be increased by photooxidative cross-linking of corneal collagen. The biophysical principles are compiled for the safe and effective application of this new treatment method. METHODS: The setting of the therapy parameters should be elucidated from the absorption behaviour of the cornea. The safety of the method for the endothelium cells and the lens will be discussed. The induced cross-links are shown to be the result of changes in the physico-chemical properties of the cornea. RESULTS: To reach a high absorption of the irradiation energy in the cornea, riboflavin of a concentration of 0.1% and UV light of a wavelength of 370 nm, corresponding to the relative maximum of absorption of riboflavin, were used. An irradiance of 3 mW/cm(2) and an irradiation time of 30 min lead to an increase of the mechanical stiffness. The endothelium cells will be protected due to the high absorption within the cornea, that means the damaging threshold of the endothelium cells will not be reached in a 400 microm thick stroma. As evidence for cross-links we can consider the increase of the biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibres. CONCLUSIONS: The therapy parameters were tested experimentally and have been proven clinically in the corneal collagen cross-linking. These parameters should be respected to reach a safe cross-linking effect without damage of the adjacent tissues.