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.

Long-term follow-up of repeated corneal cross-linking for progressive keratoconus in young patients / Acompanhamento a longo prazo do retratamento com cross-linking corneano para ceratocone em progressão em pacientes jovens

ABSTRACT Objective: To evaluate the long-term safety and efficacy of repeated corneal cross-linking in eyes of children and adolescents with progressive keratoconus. Methods: This retrospective study included nine eyes of nine consecutive patients with progressive keratoconus who underwent repeated corneal cross-linking 3.9 (range of 1.6 to 5.6) years after a primary one. All patients were followed for a mean period of 9.11 (range of 6 to 11) years after first treatment and 5.44 (range of 4 to 9) years, after corneal cross-linking retreatment. Results: Nine eyes of nine patients (six male) with progressive keratoconus underwent primary corneal cross-linking from 2009 to 2011. Despite the stability achieved with the epi-off corneal cross-linking, keratoconus continued to progress after some time. Mean time to documented evidence of keratoconus progression after primary corneal cross-linking was 3.9 (range of 1.6 to 5.6) years. All eyes were retreated as soon as progression was noted. At the last follow-up visit, 5.44 (range of 4 to 9) years after repeated corneal cross-linking, there was a significant decrease of 2.02 D in mean maximum topographic K-value (p = 0.045) and 1.95D in mean topographic K-value (p = 0.007). Conclusion: Repeated corneal cross-linking seems to be a safe and effective procedure to halt keratoconus progression after a primary corneal cross-linking failure.

RESUMO Objetivo: Avaliar a segurança e a eficácia a longo prazo da repetição do cross-linking corneano em olhos de crianças e adolescentes com ceratocone progressivo. Métodos: Estudo retrospectivo que incluiu nove olhos de nove pacientes consecutivos com ceratocone progressivo, que foram submetidos a retratamento com cross-linking corneano de 3,9 (variação de 1,6 a 5,6) anos após tratamento primário com cross-linking corneano. Todos os pacientes foram acompanhados por um período médio de 9,11 (variação de 6 a 11) anos após o primeiro tratamento e 5,44 (variação de 4 a 9) anos após retratamento com cross-linking corneano. Resultados: Nove olhos de nove pacientes (seis homens) com progressão do ceratocone foram submetidos a cross-linking corneano primário de 2009 a 2011. Apesar da estabilidade alcançada com o epi-off cross-linking corneano, o ceratocone continuou a progredir após algum tempo. O tempo médio para evidência documentada de progressão do ceratocone após cross-linking corneano primário foi de 3,9 (intervalo de 1,6 a 5,6) anos. Todos os olhos foram retratados com cross-linking corneano, assim que a progressão foi observada. Na última consulta de acompanhamento, 5,44 (variação de 4 a 9) anos após a repetição do cross-linking corneano, houve diminuição significativa de 2,02 D na média da curvatura máxima (p = 0,045) e 1,95 D na média da curvatura média (p = 0,007). Conclusão: O retratamento com cross-linking corneano parece ser um procedimento seguro e eficaz para interromper a progressão do ceratocone após falha primária do cross-linking corneano.

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

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

Repetibilidade do estudo tomográfico da córnea com Scheimpflug rotacional, em olhos normais, olhos com ceratocone e olhos com ceratocone operados por crosslinking / Repeatability of the tomographic study of the cornea with a rotational Scheimpflug in normal eyes, eyes with keratoconus and eyes with crosslinking for keratoconus

RESUMO Objetivo Avaliar a precisão da tomografia corneana com imagens de Scheimpflug (Pentacam® AXL, OCULUS, Wetzlar, Alemanha) nos padrões de escaneamento com 25 e 50 imagens, verificando sua repetibilidade e reprodutibilidade em olhos normais, com ceratocone e com ceratocone após crosslinking. Métodos Estudo prospectivo, transversal, misto, no qual foram incluídos os pacientes que tinham córneas normais, ou com ceratocone; e não tinham realizado cirurgias corneanas, com exceção do crosslinking. Foram excluídos os pacientes que tivessem realizado outras cirurgias, como implante de anel intracorneano ou transplante de córnea. Foram realizadas três medidas com 25 imagens e três medidas com 50 imagens em cada olho incluído no estudo. Resultados O estudo avaliou 54 olhos de 41 pacientes. Destes, dez (18,52%) olhos eram com córneas normais e sem cirurgia ocular prévia aleatoriamente selecionados de 5 pacientes; 22 (40,74%) olhos aleatoriamente selecionados de 18 pacientes com ceratocone, sem cirurgia ocular prévia; e 22 (40,74%) olhos com ceratocone de 18 pacientes operados por crosslinking. No estudo da repetibilidade, percebemos uma maior variação de valores em todos os índices nos pacientes com ceratocone comparados aos de pacientes com olhos normais, em grande parte dos parâmetros analisados. Conclusão Não houve diferença significativa entre os métodos de escaneamento por 25 e 50 imagens, sendo o escaneamento por 25 imagens mais conveniente. A presença de ceratocone teve impacto negativo na repetibilidade de ambos os tipos de exame, e foi grande a concordância entre os métodos nos três grupos estudados. O coeficiente de repetibilidade permite considerar a relevância clínica dos dados para avaliar a progressão de ceratocone.

ABSTRACT Objective To evaluate the accuracy of corneal tomography with Scheimpflug images (Pentacam® AXL, OCULUS, Wetzlar, Germany) in scanning patterns with 25 and 50 images, by analyzing their repeatability and reproducibility in normal eyes, eyes with keratoconus and with keratoconus after crosslinking. Methods Prospective, cross-sectional, mixed study including patients who had normal corneas, or who had keratoconus, who had not undergone corneal surgery, with the exception of crosslinking. Patients who had undergone surgery for intracorneal ring implantation or corneal transplantation were excluded. Three measurements were performed with 25 images and three measurements were performed with 50 images on each eye included in the study. Results The study evaluated a total of 54 eyes of 41 patients. Of these, 10 (18.52%) eyes had normal corneas, without previous eye surgery, 22 (40.74%) were eyes with keratoconus, without previous eye surgery, and 22 (40.74%) were eyes with keratoconus, with crosslinking for keratoconus. In the study of repeatability, we noticed a greater variation of values in all indices in patients with KC compared to those with normal eyes, in most of the parameters analyzed. Conclusion There is no significant difference between the scanning methods with 25 and 50 images. However, 25 scans has advantages that make it the main method suggested. The presence of keratoconus has a negative impact on the repeatability of both types of examination, and there is great agreement between the methods in the three groups studied. The high repeatability coefficient in some parameters suggests that these data should be used with care in the assessment of keratoconus progression.

Pediatric Crosslinking: Current Protocols and Approach.

Keratoconus (KC) is likely to be more aggressive in the pediatric population, with a higher risk of progression and visual loss. Several techniques have been proposed for corneal crosslinking (CXL) so far. The standard CXL (SCXL) technique, or the Dresden Protocol, originally developed by Wollensak et al., has been shown to be safe and effective in the pediatric KC group. With similar efficacy to the conventional method, the accelerated CXL (ACXL) protocols proposed a reduced UVA exposure time by increasing the intensity of UVA irradiation. Transepithelial CXL (TCXL), considered an "epithelium-on" method, emerged as a strategy to improve safety and reduce postoperative complications and discomfort. For thinner corneas, we can highlight the use of hypoosmolar riboflavin and new studies, such as contact lens-assisted CXL (CACXL), the epithelial-island CXL (EI-CXL), and the Sub400 protocol. In addition to the different protocols used, another factor that changes CXL results is the type of carrier used: dextran-based or hydroxypropyl methylcellulose-based (HPMC) riboflavin solutions. There are several ways to perform a CXL surgery, and it is still unclear which method is the safest and most effective in the pediatric group. This review of the literature in English, available in PubMed, provides an update on corneal CXL in the pediatric KC group, exploring the data on the techniques currently used and under investigation, including their advantages, efficacy, safety profiles, risks, and cost analyses.

Severe long-term progressive corneal remodeling after bilateral simultaneous prophylactic crosslinking and topography-guided surface ablation with mitomycin.

To report a case of a 20-year-old woman who developed massive and progressive corneal remodeling in both eyes after bilateral PRK with mitomycin and CXL as an elective refractive procedure for mild keratoconus. The patient had 6 years of follow up, initially presenting with focal steepening of up to 20 diopters on both eyes one-and-a-half- years postoperatively that spontaneously reversed over the next five years while the high order aberrations worsened. At the present time, the patient depends on bilateral scleral contact lenses for her day-to-day activities. The use of combined elective PRK with mitomycin and prophylactic CXL could lead to progressive corneal deformation. Additional reports would help to establish the role of this combination procedure among the armamentarium to visually rehabilitate patients with keratoconus.

High-Resolution Wavefront-Guided Photorefractive Keratectomy and Accelerated Corneal Crosslinking for Stabilization and Visual Rehabilitation of Keratoconus Eyes.

PURPOSE: To evaluate the visual and refractive outcomes after high-resolution wavefront-guided (HRWG) surface ablation with corneal crosslinking (CXL) in keratoconus eyes. PATIENTS AND METHODS: In this prospective, interventional case series, 47 eyes of 28 progressive keratoconus patients older than age 18 were enrolled. All patients underwent HRWG photorefractive keratectomy (PRK) with simultaneous accelerated CXL. The study parameters were manifest refraction spherical equivalent (MRSE), keratometric outcomes, uncorrected (UDVA) and corrected distance visual acuity (CDVA) at postoperative 6 and 12 months. RESULTS: There was improvement in mean MRSE from -2.39±1.89 D preoperatively to -0.13 ± 0.68 D at 12 months, with corresponding improvement in UDVA from 0.77 ± 0.35 logMAR to 0.08 ± 0.12 logMAR and CDVA from 0.10 ± 0.11 logMAR to 0.02 ± 0.04 logMAR. Preoperative flat and steep keratometry (K) were 4wct 32.49 ± 1.67 D and 45.94 ± 2.10 D, respectively, and at postoperative 12 months were 41.36 ± 2.08 D and 42.65 ± 2.78 D, respectively. At postoperative 12 months, visual and refractive outcomes were maintained. Comparisons between preoperative and postoperative 12 month timepoints were statistically significant for all parameters. CONCLUSION: Simultaneous wavefront-guided PRK followed by CXL is a promising treatment for the visual rehabilitation of keratoconus patients.

Actualización sobre factores de riesgo asociados a daño corneal post Cross-Linking / Update on risk factors associated with corneal damage post Cross-Linking

El Cross-Linking corneal es un procedimiento utilizado en oftalmología principalmente para el tratamiento del queratocono, la ectasia corneal más frecuente. A pesar de su baja tasa de complicaciones, no es una técnica exenta de ellas. Entre las principales complicaciones se encuentran el haze y el melting corneal, ambas poseen una fisiopatología que no está totalmente esclarecida. Se realizó una revisión bibliográfica sobre la asociación entre el uso de quinolonas y el daño corneal frente a la exposición de luz UV. También se plantearon factores inherentes al paciente que se han relacionado al aumento de complicaciones. Se determinó que la radiación UV produce daños en aquellos tejidos sometidos previamente a tratamiento con quinolonas siendo de suma importancia la correcta anamnesis para seleccionar a los candidatos al procedimiento. (AU)

Corneal Cross-Linking is a procedure used in ophthalmology mainly for the treatment of keratoconus, the most frequent corneal ectasia. Despite its low complication rate, it is not an exempt technique. Among the main complications are haze and corneal melting, both have a pathophysiology that is not fully clarified. A bibliographic review of the association between the use of quinolones and corneal damage versus UV light exposure was performed. Inherent patient factors that have been related to increased complications were also raised. It was determined that UV radiation causes damage to these tissues, sometimes prior to quinolone treatment, with the correction of the anamnesis being of utmost importance to select the candidates for the procedure.

Late progressive corneal flattening, haze and visual loss after eccentric crosslinking for Pellucid marginal degeneration.

PURPOSE: Pellucid marginal degeneration (PMD) is a rare disease that is often mistaken for keratoconus but can similarly be treated with corneal collagen crosslinking (CXL). We report a case followed though 6 years of progressive irregular corneal flattening and thinning in both eyes (OU) after eccentric CXL for PMD. OBSERVATION: A 46-year-old man with bilateral PMD and corrected distance visual acuity (CDVA) of 20/20 (-2.00x80) in the right eye (OD) and 20/30 (+3.50-5.25x105) in the left eye (OS) underwent conventional 9 mm eccentric CXL in OU and intrastromal corneal ring implantation in the OS. An uneventful first year postoperative follow-up showed stabilization of the ectasia. In subsequent years, progressive inferior flattening was observed with decreased CDVA, corneal thinning and worsening of the haze. At the last follow-up, his CDVA was 20/40 (+5.00-2.00x55) OD and 20/60 (+6.00-1.50x80) OS. CONCLUSION AND IMPORTANCE: The current report highlights the notion that mid- and long-term evaluations of customized crosslinking techniques may reveal progressive flattening and corneal irregularity.

Correlation between corneal stromal demarcation line depth and topographic outcomes after two pulsed-light-accelerated crosslinking protocols.

PURPOSE: To report the visual and topographic outcomes of two pulsed-light-accelerated CXL (A-CXL) protocols at a 12-month follow-up and their correlation with the corneal stromal demarcation line (DL) depth. PATIENTS AND METHODS: Retrospective comparative cohort of patients with documented progressive keratoconus were included. Two epi-off pulsed-light [1s on-1s off] A-CXL protocols were compared: irradiance 30*8 and 45*5:20 (fluence 7.2 J/cm2). UDVA, CDVA, spherical equivalent (SE), topographic astigmatism, Kmin, Kmax, Km, central corneal thickness (CCT), thinnest pachymetry (TCT) and endothelial cell density (ECD) were measured preoperatively and months 1, 3, 6 and 12 postoperative. Corneal DL was measured 1 month postoperatively using anterior segment optical coherence tomography. RESULTS: Fifty eyes (27 patients): 22 eyes in group A-CXL (30*8), 28 eyes in group A-CXL (45*5:20). Mean age (years) was 19.04±4.71 and 20.32±4.57. DL depth (µm) at month 1 was 200.63±10.01 µm and 184.53±19.68 µm for group A-CXL (30*8) and group A-CXL (45*5:20), respectively (p<0.001). Significant improvement in CDVA, topographic astigmatism, Kmin, Kmax and Km was observed in both groups (no significant difference between groups) and no significant changes were observed in CCT, TCT and ECD with regard to baseline. Over 85% of the eyes in both protocols achieved stabilization or improvement in maximum K at the end of the follow-up. No significant correlations between DL and any visual or topographic outcomes were observed at 12 months. CONCLUSION: No correlation between DL depth and visual or topographic outcomes was observed on either protocol. Although significant improvement on CDVA, topographic astigmatism, Kmin, Kmax and Km was observed in both groups at 12 months, further research is needed to assure safety and effectiveness at stabilizing keratoconus progression.

Effect of accelerated corneal crosslinking on ocular response analyzer waveform-derived parameters in progressive keratoconus / Efeito do crosslimking corneano acelerado nos parâmetros derivados da forma de onda do analisador de resposta ocular no ceratocone progressivo

ABSTRACT Purpose: To evaluate the effect of accelerated corneal crosslinking on corneal biomechanics with an ocular response analyzer in patients with progressive keratoconus. Methods: In this retrospective study, 50 eyes of 45 patients with progressive keratoconus who underwent accelerated corneal crosslinking were evaluated with ocular response analyzer waveform parameters before and one year after corneal crosslinking. Paired two-tailed Student's t-test was performed to compare the parameters before vs. after corneal crosslinking. Results: Mean patient age was 17.6 ± 3.6 (range 9-25) years. A significant increase was observed in p1 area, p2 area, h2, and dive2 values. No significant difference in corneal hysteresis, corneal resistance factor, or other waveform-derived parameters was observed at one year postoperatively. Conclusion: For estimating the effect of accelerated corneal crosslinking on corneal biomechanics, parameters such as p1 area, p2 area, h2, and dive2 are more sensitive than corneal hysteresis and corneal resistance factor. These results may help us to find out which corneal crosslinking method is most effective for stiffening the cornea.

RESUMO Objetivo: Avaliar o efeito do cross-linking corneano acelerado na biomecânica corneana com analisador de resposta ocular em pacientes com ceratocone progressivo. Métodos: Neste estudo retrospectivo, 50 olhos de 45 pacientes com ceratocone progressivo submetidos à cross-linking corneano acelerado foram avaliados com os parâmetros da forma de onda do analisador de resposta ocular antes e um ano após o tratamento com cross-linking corneano. O teste t de Student pareado bicaudal foi realizado para comparar os parâmetros antes e depois do cross-linking corneano. Resultados: A média de idade dos pacientes foi de 17,6 ± 3,6 (variação de 9 a 25) anos. Um aumento significativo foi observado nos valores de p1area, p2area, h2 e dive2. Nenhuma diferença significativa foi encontrada na histerese da córnea, fator de resistência da córnea ou outros parâmetros derivados da forma de onda foi observada em um ano de pós-operatório. Conclusão: Para estimar o efeito do cross-linking corneano acelerado na biomecânica corneana, parâmentros como p1area, p2area, h2 e dive2 são mais sensíveis que histerese da córnea e fator de resistência corneana. Esses resultados podem nos ajudar a descobrir qual método cross-linking corneano é mais eficaz no enrijecimento da córnea.

Two-year follow-up of corneal cross-linking and refractive surface ablation in patients with asymmetric corneal topography.

AIMS: To evaluate the safety and efficacy of corneal cross-linking (CXL) followed by photorefractive keratectomy (PRK) for refractive correction in patients with bilateral asymmetric topography. METHODS: Forty-four patients (88 eyes) were enrolled in this prospective randomised clinical trial. CXL with subsequent PRK after 6 months was performed in one eye (study group), and PRK alone was performed in contralateral eyes (control group). Patients were followed for 24 months after PRK. Outcome measures investigated included visual acuity (VA), refraction, aberrometry, topography, pachymetry and endothelial cell count. Groups were compared with linear mixed regression and repeated measures logistic regression. Multiple comparison adjustment with the Holm procedure was performed. RESULTS: At baseline, the logMAR VA (best spectacle corrected) in study and control groups was 0.12±0.13 (mean±SD) and 0.08D±0.14, respectively, and axial inferior-superior index (IS) (topographic IS) in study and control groups were 0.59D±0.31D and 0.58D±0.32D, respectively. After 24 months, a mean under correction of -0.50D was observed in both groups. Change from baseline in logMAR VA in study and control groups was 0.00D±0.08D and -0.02D±0.10D, respectively. Frequency of haze at 30 months in study and control group eyes was, respectively, 18.2% and 4.6% (p=0.05). There was no statistical difference between groups in spherical aberration and coma after adjustment for multiple comparisons. CONCLUSIONS: Non-simultaneous CXL followed by PRK may be performed safely, and refractive results over a 2-year follow-up are highly similar in virgin and previously cross-linked corneas. Despite using mitomycin C, corneal haze can be significantly higher in the first year after PRK in eyes pretreated with CXL.

Trans-epithelial accelerated corneal cross-linking for keratoconus in children.

The aim of the study is to evaluate the safety and efficacy of trans-epithelial accelerated corneal cross-linking (TE-ACXL) in children with progressive keratoconus. Retrospective, case-series of 23 eyes of 14 children who underwent TE-ACXL. Evaluations were performed at baseline and 1, 3, 6, 12 and 18mo postoperatively. Mean follow-up time of 23.82±3.15mo and mean age was 13.7±1.4y (range 11 to 16y). Mean preoperative uncorrected distance visual acuity changed from 0.92±0.45 logMAR (20/160) to 0.71±0.40 logMAR (20/100) (P=0.001). Mean keratometry (Km) changed from 53.87± 6.03 to 53.00±5.81 (P=0.001). Pachymetry did not have significant changes at last follow-up (P=0.30). The mean preoperative sphere was -5.58±2.48 and -4.89±4.66 D (P=0.11) at last follow-up; refractive cylinder from -5.58±2.48 to -5.02±2.23 (P=0.046). In conclusion, tomographic and refractive stability are shown in over 91% of eyes with pediatric progressive keratoconus who underwent TE-ACXL.

Phototoxic Effect of Topical Fluoroquinolones Administered Before Corneal Crosslinking in a Murine Model.

PURPOSE: Corneal crosslinking by UV light (UV-CXL) has become a popular treatment for keratoconus and corneal ectasia. Fluoroquinolones (FQs), commonly administered topically before UV-CXL, are known to be phototoxic to the skin and lens. The purpose of this study was to investigate phototoxic effects of topical FQ treatment on murine corneas before UV-CXL, in which the corneal epithelium was kept intact. METHODS: Murine corneas were treated with various antibiotics with or without riboflavin before UV-CXL. At 24 h, the animals were sacrificed, and the corneas were analyzed for histologic evidence of inflammation and apoptosis and for expression of apoptosis markers BAX and caspases 3 and 9 and for expression of matrix metalloproteinase 9 (MMP-9). Spectrofluorometric analysis was performed. RESULTS: Corneas treated with topical FQ with or without riboflavin before UV-CXL showed mild corneal stromal inflammation, apoptosis by both terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased expression of BAX gene and caspases 3 and 9 by densitometric analysis. Untreated corneas, corneas treated with azithromycin before UV-CXL, and corneas undergoing UV-CXL without any antibiotic or riboflavin pretreatment showed normal histology, no staining for apoptosis, and no increased production of apoptosis markers by polymerase chain reaction. CONCLUSIONS: The phototoxic effects of FQs on the cornea may lead surgeons to consider another antibiotic class for prophylaxis against infectious keratitis in UV-CXL. These effects, along with the known cytotoxic effects of FQs independent of UV radiation, may contribute to some of the complications of corneal UV-CXL. Dosage studies may be warranted.

Characterization of Rabbit Corneas Subjected to Stromal Stiffening by the Açaí Extract (Euterpe oleracea).

PURPOSE: In this study, we characterized rabbit corneas subjected to corneal cross-linking (CXL) with açaí extract compared with a riboflavin photo-stimulated procedure. MATERIALS AND METHODS: The corneas of the slaughterhouse rabbits were divided into three groups: control, consisting of untreated corneal samples; riboflavin/UVA, where corneas were treated with 0.1% riboflavin photo-stimulated at 365 nm as the standard protocol; and açaí, where the samples were subjected to 4% açaí extract for 0.5-2 h. After the CXL procedure, corneas of the three groups were characterized by analyzing their elastic modulus and thermal denaturation profile. RESULTS: The elastic modulus at 3% strain showed an approximately threefold increase in the riboflavin/UVA group and 10.5 times in the corneas treated with 4% açaí extract for 2 h, compared with the control group (p < 0.01). The denaturation temperature values of the two groups of crosslinked corneas increased significantly (p < 0.05) and were more pronounced in the açaí group. CONCLUSIONS: The açaí extract was effective in promoting CXL in rabbit corneas as characterized by the different techniques.

Corneal Cross-Linking (with a Partial Deepithelization) in Keratoconus with Five Years of Follow-Up.

We performed a retrospective interventional case series including 80 eyes of 48 patients with keratoconus (KC) who were treated with modified corneal cross-linking (CXL) for KC (with a partial deepithelization in a pattern of stripes). The average follow-up was 5.8 years (with a minimum of 5 years). At the last follow-up visit, compared with preoperative values, there were no significant changes in spherical equivalent, average keratometry, corneal thickness, corneal hysteresis, or corneal resistance factor. The distance-corrected visual acuity was 20/39 preoperatively and 20/36 postoperatively (P = 0.3). The endothelial cell count decreased by 4.7% (P < 0.005). These findings suggest that this modified corneal CXL technique is a safe and effective alternative to halt the progression of KC up to five years after the procedure. However, some concerns remain as to whether this technique can affect in some degree the corneal endothelial cells.

Tratamiento de queratitis micótica con voriconazol y crosslinking corneal: reporte de un caso / Successful treatment of fungal keratitis with voriconazole and crosslinking: a case report

La queratitis micótica es una causa importante de morbilidad y discapacidad visual, especialmente en los países en vía de desarrollo. Se considera una entidad de difícil manejo, con evolución usualmente tórpida, debido a diversos factores, dentro de los cuales destacan la agresividad de la infección, la dificultad para orientar una terapia basada en los resultados de las pruebas microbiológicas, la ausencia de un protocolo terapéutico estandarizado respaldado por estudios con buen nivel de evidencia, que garantice cubrimiento adecuado contra todos los tipos de hongos, disminucíon de la progresión de la infección, y mejoría clínica. Actualmente ante la presencia de casos con evolución tórpida tras el manejo médico se recurre a otras asociaciones en busca de buenos resultados, es ahí donde juega un papel importante el uso de crosslinking corneal como terapia adyuvante en el manejo de casos refractarios o que no tengan una adecuada evolución con la terapia habitual tópica. Presentamos el caso de un paciente joven de sexo masculino, quien fue tratado exitosamente con una terapia combinada consistente en Voriconazol tópico, sistémico y ante la no adecuada respuesta, se recurrió a un crosslinking corneal, lo cual se encuentra en concordancia con diversos reportes y estudios publicados en la literatura, que sugieren que el Voriconazol combinado con crosslinking corneal, podrían ser considerados una alternativa eficiente en el manejo de casos difíciles o que no tengan buena respuesta a la terapia antimicótica tradicional, teniendo en cuenta que aún hay mucho por investigar en este campo.

Fungal keratitis is an important cause of morbidity and visual disability primarily in developing countries. It is considered as a difficult to manage entity, usually with a torpid progression due to various factors, among these factors are the aggressiveness of the infection, the difficulty for orienting a therapy based on the results of the microbiological tests, the absence of a standardized therapeutic protocol backed by studies with a good level of evidence that guarantees adequate covering against all types of fungus, reduction of the infection progression and clinical improvement. Currently in response to cases with torpid progression after medical management you resort to other combinations in search of good results, this is where the use of corneal crosslinking plays an important role as adjuvant therapy in the treatment of refractory cases or in those cases that don´t have an adequate progress with the habitual topical therapy. We hereby present the case of a male young patient who was successfully treated with a combined therapy consisting of topic Voriconazole, systemic and in the presence of a non-adequate response, we resorted to a corneal crosslinking, which is in line with different reports and studies published in the literature that suggest that the Voriconazole combined with corneal crosslinking might be considered as an effective alternative in the treatment of intractable cases or cases that do not have a good response to the traditional antifungal therapy, bearing in mind that there is still too much research to be done in this field.