Dysregulation of Receptor for Advanced Glycation End Products (RAGE) Expression as a Biomarker of Keratoconus

Background. Because of the implications of Receptor for Advanced Glycation End Products (RAGE) in keratoconus (KC), we describe a differential expression of RAGE transcripts and proteins in corneal tissues and tears of KC and healthy patients. Methods. Using a case-controlled study, corneal epitheliums and tears of KC and healthy subjects were obtained during corneal collagen cross-linking and photorefractive keratectomy (PKR) and during usual consultations. Quantitative reverse transcription (RT-qPCR) and Western-Blot were performed to analyze RAGE transcripts and proteins’ expression in corneal tissues and tears. Results. One hundred and six patients were included in this study. The characteristics of the patients were as follows: 56 KC (25 corneal epithelium and 31 tears) and 50 control subjects (25 corneal epithelium and 25 tears). Transcripts of RAGE, HMGB1, and S100 family ligands were quantified by RT-qPCR, identifying a significantly higher expression of RAGE and HMGB1 in the healthy group than in the KC group ( p = 0.03 and 0.04, respectively). Western Blot showed a significantly higher fl-RAGE expression in KC corneal epithelium than control ( p < 0.001 ) and lower s-RAGE expression in KC tears than control ( p = 0.04 ). Conclusions. Linked with the inflammatory process occurring in KC pathophysiology, we propose for the first time that the RAGE expression (total and truncated forms of receptor and ligands) in KC corneal tissues and tear samples provides viable biomarkers.

Keratoconus in Children. Мodern Treatment Options

Objective: to evaluate the results of corneal collagen crosslinking in children with keratoconus.Patients and methods. Since 2017, 125 children aged 4 to 17 years have been under observation, who have applied to the Eye Microsurgery named after Academician S.N. Fedorov with complaints of reduced visual acuity and, in some cases, the inability to select optical correction. All patients were examined, including using high-tech methods (Sheimpflug camera, OCT). Based on the anamnesis and the data obtained, the diagnosis of keratoconus stage I–III was made. Corneal collagen crosslinking was performed in 30 patients with stage II–III.Results. The study included 30 eyes of 30 patients (21 (68 %) boys, 9 (32 %) girls) with a median age — 16 (15; 17) years (12 to 17 years), who underwent accelerated “epi-off” crosslinking. No intra-and postoperative complications were observed. 12 months after CXL, there was a slowdown in the progression of keratoconus in children (minimum corneal thickness before surgery 460.00 (445.00; 477.00), after surgery 457.00 (441.00; 477.00), p = 0.112; K1 before surgery 44.60 (43.20; 46.90), after surgery 44.60 (42.90; 46.50), p = 0.481; K2 before surgery 48.30 (47.30; 51.25), after surgery 48.20 (47.21; 49.20), p = 0.779; elevation of the posterior surface before surgery 25.00 (18.00; 42.00), after surgery 26.00 (21.00; 42.00), p = 0.074, and increased visual acuity (NCOZ from 0.30 (0.05; 0.40) to 0.30 (0.20; 0.40) (p = 0.039) and MCOZ from 0.60 (0.40; 0.80) to 0.60 (0.50; 1.00) (p = 0.010)).Conclusion. 1. Keratoconus is also found in the child population. 2. Timely cross-linking of corneal collagen can slow the progression of keratoconus in children

Ultraviolet crosslinking of corneal collagen in patients with thin cornea. Literature review

For the treatment of progressive keratoconus in the early stages, corneal collagen crosslinking is currently actively used. This technique is based on the stabilization of the pathological process by increasing the biomechanical properties of the own cornea. The thickness of the cornea less than 400 microns significantly limits the possibility of a standard cross-linking procedure performing.The article analyzes the literature data on the use of various methods of corneal crosslinking with a corneal thickness of less than 400 microns, which signifi cantly limits the possibilities of the standard procedure.It is known, that during crosslinking, at the initial stage, de-epithelialization of the cornea is performed, which, in the postoperative period, leads to a pronounced corneal syndrome. This determined the direction of the fi rst modifi cations of the technique associated with the use of partial de-epithelialization or its complete absence. Later, during cross-linking of “thin” corneas, techniques with the use of additional covering materials were actively used in order to replenish the missing corneal tissue of the patient during the UV irradiation procedure. Among them are the use of a soft contact lens without an ultraviolet fi lter, the use of a corneal lenticule obtained after SMILE surgery, the use of a protective fl ap of the donor cornea obtained using a femtosecond laser from the residual stroma of the corneal disc after descemet membrane transplantation or posterior lamellar keratoplasty. The variety of the proposed modifications and the ongoing search for better options indicate the demand for this technology and the need for further research, taking into account the individual characteristics of the patient’s ectasia.

Preliminary Characterization of Predictive Factors of the Visual Change after Epi-On and Epi-Off Corneal Collagen Crosslinking Techniques

Purpose. To investigate the potential predictive factors of the visual change achieved with accelerated epi-on and epi-off corneal collagen crosslinking (CXL) in keratoconus. Methods. This retrospective comparative study analyzed 67 eyes treated with an accelerated epithelium-on (epi-on group) and epithelium-off (epi-off group) CXL. The clinical outcomes were evaluated and compared during a 1-year follow-up. Likewise, the relationship of the change achieved with both CXL techniques in the corrected distance visual acuity (CDVA) with different preoperative data was investigated. Results. The mean CDVA change at 3 months postoperatively was −0.04 ± 0.19 and −0.07 ± 0.25 in the epi-on and epi-off groups, respectively ( p = 0.809). In the epi-on group, this change was significantly correlated with the preoperative apical (r = −0.375, p = 0.045) and central corneal thickness (r = −0.402, p = 0.031). In the epi-off group, the CDVA change was significantly correlated with not only the preoperative apical (r = 0.402, p = 0.028) and central corneal thickness (r = 0.367, p = 0.046) but also with some topometric and aberrometric indices (r ≤ −0.374, p ≤ 0.042). Furthermore, the change in CDVA in the epi-on group could be predicted from age, preoperative refractive astigmatism J45 component, anterior corneal asphericity, and posterior corneal high order aberration root mean square ( p = 0.002, R2 = 0.503). In the epi-off group, the CDVA change could be predicted from the preoperative minimum corneal thickness and magnitude of the vertical anterior corneal primary coma component ( p = 0.001, R2 = 0.446). Conclusions. Clearly, different predictive factors of the visual change induced with the accelerated epi-on and epi-off CXL techniques are present, suggesting a different mechanism of action for stiffening the cornea and inducing changes in this structure.

Mueller Matrix-Based Approach for the Ex Vivo Detection of Riboflavin-Treated Transparent Biotissue

Corneal collagen cross-linking is an established procedure for the treatment of certain eye diseases which is applied to enhance the mechanical stability of such biotissue without deteriorating its functionality. However, being transparent, the optical analysis of the outcome of such treatments is cumbersome and relies on relatively expensive experimental equipment. We aim to apply the Mueller matrix polarimetry for the detection of photo-induced collagen cross-linking in transparent biotissue after treatment with riboflavin and UV irradiation. A simple Mueller matrix polarimetry setup could provide a fast and non-invasive analysis of transparent media to sensitively detect small photo-induced cross-linking effects in biotissue. We demonstrated the current capabilities of the approach on non-planar porcine cornea samples ex vivo. We reported the distinction between untreated and riboflavin-treated samples. The differences observed were correlated with the variation of certain Mueller matrix elements and parameters derived from the decomposition. The measurement data show variation in the cross-linked and non-cross-linked samples, although the effect of the UV treatment on the riboflavin-treated samples was not at the same level of significance yet and needs further investigation. The Mueller matrix measurement represents a promising approach for the detection of the effects of corneal collagen cross-linking. Further studies with a larger sample number are required to validate this approach. In the future, this could enable the reliable and non-invasive detection of photo-induced effects in biotissue and open the possibility for in vivo application, e.g., in eye disease treatment or the detection of scar collagen development.

Corneal Epithelial Remodeling After Femtosecond Laser-Assisted in Situ Keratomileusis Combined with Intraoperative Accelerated Corneal Collagen Crosslinking for Myopia: A Retrospective Study

Background This study analyzed regional corneal thickness remodeling, biomechanical properties, and visual outcomes after femtosecond laser-assisted in situ keratomileusis combined with intraoperative accelerated corneal collagen crosslinking (LASIK Xtra) for myopia. Methods This retrospective study comprised 21 consecutive patients (18 women and 3 men; 42 eyes) who were treated with LASIK Xtra. All treatments were performed with ultraviolet-A (energy, 2.7 J/cm2; irradiance, 30 mW/cm2), using continuous (90 s) illumination. Postoperative values of corneal biometrics and visual outcomes were compared with preoperative values. Corneal thickness changes were evaluated using anterior segment optical coherence tomography. All patients were followed up for 12 months postoperatively. Preoperative and postoperative data were compared statistically using the paired t-test for normally distributed parameters and the Wilcoxon rank-sum test and Friedman analysis of variance with Bonferroni correction for non-normally distributed data. Results Uncorrected distance visual acuity (UDVA) significantly improved at 6 months after surgery (P < 0.001). The central and inner regional corneal epithelial thickness significantly increased after LASIK Xtra (P < 0.05 for all), while peripheral corneal epithelial thickness remained stable at 12 months after surgery. There was also a statistically significant decreased in the stromal thickness at most locations (P < 0.05 for all), except in the outer superior and outer superior-temporal regions. Conclusion LASIK Xtra provided predictable postoperative UDVA, corneal curvature, and corneal biomechanical stability. Since the retrospective study results depended on the cohort members’ past information, it is inferred and confirmed that regular corneal thickness remodeling occurred after treatment.