Model Systems for Evidencing the Mediator Role of Riboflavin in the UVA Cross-Linking Treatment of Keratoconus.

Riboflavin under UVA radiation generates reactive oxygen species (ROS) that can induce various changes in biological systems. Under controlled conditions, these processes can be used in some treatments for ocular or dermal diseases. For instance, corneal cross-linking (CXL) treatment of keratoconus involves UVA irradiation combined with riboflavin aiming to induce the formation of new collagen fibrils in cornea. To reduce the damaging effect of ROS formed in the presence of riboflavin and UVA, the CXL treatment is performed with the addition of polysaccharides (dextran). Hyaluronic acid is a polysaccharide that can be found in the aqueous layer of the tear film. In many cases, keratoconus patients also present dry eye syndrome that can be reduced by the application of topical solutions containing hyaluronic acid. This study presents physico-chemical evidence on the effect of riboflavin on collagen fibril formation revealed by the following methods: differential scanning microcalorimetry, rheology, and STEM images. The collagen used was extracted from calf skin that contains type I collagen similar to that found in the eye. Spin trapping experiments on collagen/hyaluronic acid/riboflavin solutions evidenced the formation of ROS species by electron paramagnetic resonance measurements.

Ultrasound biomicroscopy as a vital tool in occult phacomorphic glaucoma.

Ultrasound is a fundamental tool used in all medical specialties, including ophthalmology. Nowadays, ultrasound biomicroscopy (UBM), a method with higher resolution, allows the investigation of in vivo details of the anterior segment of the eye at microscopic resolution. The examination is especially useful in patients with secondary glaucoma that involves a lens component such as phacomorphic glaucoma and occult phacomorphic glaucoma (OPG). The purpose of this paper was to familiarize audience with UBM and the importance of this investigation in OPG, by presenting a series of cases in which performing an UBM was vital because it provided the information needed in order to safely accomplish a curative surgical treatment that preserved our patients' visual acuity.

Overexpression of Tear Inflammatory Cytokines as Additional Finding in Keratoconus Patients and Their First Degree Family Members.

Keratoconus is a progressive corneal ectasia that may lead to severe visual impairment due to the irregular astigmatism caused by corneal thinning. In addition to its association with atopy, eye rubbing, or genetic component, late reports suggest the involvement of inflammation in the pathogenesis of the disease. Our aim was to determine the concentration of IL-4, IL-6, IL-10, RANTES, IFN gamma, and TNF alpha in the tear film of patients with keratoconus and their first degree family members. We analyzed forty-eight participants in an observational cross-sectional study. The diagnosis of keratoconus had to be confirmed in addition to a minimum of 47 D corneal refractive power by corneal topography readings provided by a Placido-based topography system and analysis of the pattern: irregular astigmatism with an asymmetric "bow-tie." As for the other groups, the most important diagnosis criteria were a normal topographic pattern with a regular astigmatism. 17 keratoconus patients, 16 relatives, and 15 controls were recruited after clinical assessment as part of the research. The cytokine's mean values were similar in the keratoconus group and the relatives' samples but significantly higher compared to the controls. Important differences were found in IL-4 levels between keratoconus patients and relatives and between relatives and controls (mean difference of 302.42, p < 0.0016 and 219.16, p < 0.033, Tukey's HSD procedure). In the keratoconus group, using the CORR procedure, we found statistically strong correlations of IL-6 lacrimal concentrations with the disease stage (r = 0.56, p < 0.01), keratometry (r = 0.55, p < 0.02), pachymetry (r = -0.64, p < 0.048), and corneal hysteresis (r = -0.53, p < 0.02). Cytokine overexpression may be relevant for the inflammatory etiology of keratoconus. In conclusion, in the case of some first degree family members, the elevated tear biomarkers may represent a supplementary risk factor.

The importance of corneal biomechanics in assessing first degree family members of keratoconus patients.

Aim: to determine the values of biomechanical parameters (corneal hysteresis - CH, corneal resistance factor - CRF and keratoconus match index - KMI) in patients with keratoconus and their first degree family members. The purpose of the present study was to investigate the importance of assessing corneal biomechanics in subjects at risk of developing the primary ectasia. Materials and methods: 48 participants divided into three groups were analyzed in an observational study after a complete ophthalmological exam with the primary focus on Ocular Response Analyzer. Results: The mean values of CH, CRF, and KMI in the group of relatives were lower compared with the controls but higher when compared with keratoconus patients. We noted significant differences of CH and CRF between all three groups, while in the case of KMI, only the keratoconus group presented statistically significant differences compared with the relatives, respectively with the healthy subjects. Conclusions: the decreased values of CH and CRF may raise the question whether corneal biomechanics could be an adjuvant tool in the screening of a first-degree family member of a keratoconus patient in the attempt of the early detection of a possible forme fruste keratoconus.

Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus.

Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus.

Stem potentialities of the human iris - An in situ immunohistochemical study.

According to recent findings multiple human tissues harbor stem cells which, in turn, have different levels of stemness. We performed an immunohistochemical study on paraffin-embedded samples to test if the in situ stromal cells of the iris of the human eye (EI) have immune stem/progenitor phenotypes. Eviscerated post-traumatic eyes from eight patients were studied. These irises were found to contain fibroblastoid stromal cells with a CD34+/CD45+/CD105+/CD117+/DOG1+/PDGFR-α+/vimentin+/nestin-/collagen III- phenotype. These were assumed to be possible stem/progenitor cells involved in physiological processes of iridial stromal maintenance. All the vascular endothelia were CD34+/CD105+/vimentin+. Newly formed nestin+ endothelia were also found; this finding was supported by evidence of filopodia-projecting CD34+ endothelial tip cells, which demonstrated active processes of sprouting angiogenesis. The phenotype of the stromal cells also suggests a role of the circulating fibrocytes in iridial regenerative processes.