Tear Mediators NGF along with IL-13 Predict Keratoconus Progression.

Purpose: To find immunomediator combinations which could sensitively indicate keratoconus progression.Methods: Tear samples of 42 patients with keratoconus were collected at baseline and at the end of a one-year follow-up. The concentrations of 13 mediators were measured by CBA. Based on Pentacam HR examination, eyes were divided into a non-progressive and a progressive group.Results: At the end of the follow-up, significant differences were observed in the release of IFNγ, IL-13, IL-17A, CCL5, MMP-13 and PAI-1 between the two groups. Changes in five Pentacam parameters correlated positively with changes in IFNγ, IL-13, IL-17A, CXCL8, CCL5, TIMP-1 and t-PA. We found that tear level of IL-13 in combination with NGF can predict the progression of keratoconus with 100% specificity and 80% sensitivity.Conclusion: The findings of our longitudinal study may underscore the importance of NGF and IL-13 tear levels in the prediction of keratoconus progression.

Effects of aging on corneal parameters measured with Pentacam in healthy subjects.

Our purpose was to prospectively analyze the age-related changes of corneal Scheimpflug parameters in healthy subjects. Thirty-five eyes of 35 volunteers (age 14-67 years) were investigated with an average interval of 3.6 years. Changes of corneal parameters (flattest keratometric reading at anterior (K1F) and posterior surface (K1B), steepest keratometric reading at anterior (K2F) and posterior surface, anterior astigmatism, posterior astigmatism (AstigB), flat axis of anterior and posterior astigmatism (AxisB), thinnest pachymetric value (PachyMin), corneal volume (CV10-mm)) were analyzed. K1F and K2F decreased significantly during observation and showed stronger decrease in younger than in older individuals. Higher values proved to be more stable. K1B decreased significantly and the degree of decrease was dependent on its baseline value and age: in young subjects low values increased, high values decreased. AstigB decreased significantly and showed a baseline-dependent significant increase from lower and a significant decrease from higher initial values. Over time, the mean AxisB shifted significantly. PachyMin and CV decreased significantly with age, especially from higher baseline values in younger subjects. The results of this longitudinal study suggest that both corneal surfaces change significantly with age. We demonstrate for the first time that age and baseline values influence age-related changes of corneal parameters.

Femtosecond laser-assisted keratoplasty combined with cataract extraction in a patient with keratoconus and oculocutaneous albinism.

In this study, we present a case of a 58-year-old male patient with oculocutaneous albinism, keratoconus, total cataract, and glaucoma originating from father-daughter incest. He underwent femtosecond laser-assisted keratoplasty with "open-sky" cataract extraction and posterior chamber intraocular lens implantation. One week after surgery his uncorrected visual acuity improved from hand motion to 20/200. Six months later corneal K values were 49.1 D in the flat and 50.0 D in the steep meridian. The graft had a central corneal thickness of 488 µm and was well fitted. The patient's quality of life improved substantially due to the surgery. To the best of our knowledge, this is the first report on the association of albinism with advanced keratoconus, total cataract, and glaucoma. Moreover, no previous report on femtosecond laser-assisted keratoplasty using VisuMax femtosecond laser system with "open-sky" cataract extraction is available in the literature. The VisuMax femtosecond laser-assisted keratoplasty ensures fast patient rehabilitation in such challenging cases.

Tear Mediators in Corneal Ectatic Disorders.

PURPOSE: To compare the concentrations of 11 tear mediators in order to reveal the biochemical difference between pellucid marginal degeneration (PMD) and keratoconus (KC). METHODS: We have designed a cross-sectional study in which patients with corneal ectasia based on slit-lamp biomicroscopy and Pentacam HR (keratometry values (K1, K2, Kmax), astigmatism, minimal radius of curvature (Rmin), corneal thickness (Apex and Min), indices (surface variation, vertical asymmetry, keratoconus, central keratoconus, height asymmetry and decentration)) were enrolled. Eyes of keratoconic patients were similar to the PMD patients in age and severity (K2, Kmax and Rmin). Non-stimulated tear samples were collected from nine eyes of seven PMD patients, 55 eyes of 55 KC patients and 24 eyes of 24 healthy controls. The mediators' (interleukin -6, -10, chemokine ligand 5, -8, -10, matrix metalloproteinase (MMP) -9, -13, tissue inhibitor of metalloproteinases (TIMP)-1, tissue plasminogen activator, plasminogen activator inhibitor, nerve growth factor) concentrations were measured using Cytometric Bead Array. RESULTS: MMP-9 was the only mediator which presented relevant variances between the two patient groups (p = 0.005). The ratios of MMP-9 and TIMP-1 were 2.45, 0.40 and 0.23 in PMD, KC and the controls, respectively. CONCLUSION: As far as we are aware, this is the first study that aims to reveal the biochemical differences between PMD and KC. Further studies of biomarkers to investigate the precise role of these mediators need to be defined, and it is important to confirm the observed changes in a larger study to gain further insights into the molecular alterations in PMD.

Scheimpflug Imaging Parameters Associated with Tear Mediators and Bronchial Asthma in Keratoconus.

Purpose. To determine associations between mediators in tears in the whole spectrum of keratoconus (KC); to explore connections between mediators and Scheimpflug parameters; to examine correlations between Scheimpflug parameters and bronchial asthma. Methods. Tear samples were collected from 69 patients and 19 controls. Concentrations of mediators-IL-6, -10; CXCL8, CCL5; MMP-9, -13; TIMP-1; t-PA, PAI-1-were measured by Cytometric Bead Array. Measured Pentacam parameters include keratometry values (K 1, K 2, K max), corneal thickness (Pachy Pupil, Apex, Min), and elevations and indices (including Belin-Ambrósio deviation (BAD-D)). Results. A number of significant positive associations were observed between pairs of mediator concentrations. Significant positive correlations were found between BAD-D and CXCL8/MMP-9 and K 2 and MMP-9. Significant negative associations were explored between Pachy Min and CXCL8/t-PA. Significant associations were found between pairs of mediators (IL-6 and CXCL8; CCL5 and CXCL8/MMP-9; TIMP-1 and MMP-9/-13/t-PA; t-PA and CXCL8/CCL5/PAI-1) and the severity of KC. Significant positive correlation between asthma and the severity of KC was explored. Conclusion. Cooperation of different mediators in tears all taking part in the complex pathomechanism of keratoconus was revealed. Our research verifies that inflammation plays a crucial role in the pathogenesis of KC. Additionally this study confirms the effect of bronchial asthma on keratoconus.

Association between mediators in the tear fluid and the severity of keratoconus.

PURPOSE: To study the association between different types of mediators in the tear fluid and topographic indices characterizing the severity of keratoconus (KC). METHODS: In this study, nonstimulated tear fluid samples were collected from 14 eyes of 11 patients with KC. The following indices were measured by corneal topography: maximum K value, average K value, Klyce/Maeda keratoconus index (KCI), Smolek/Klyce keratoconus severity index, opposite sector index, center/surround index, keratoconus prediction index and standard deviation of corneal power. The concentrations of interleukin (IL)-6, IL-13, CXCL8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5, regulated and normal T cell expressed and secreted), matrix metalloproteinase-9 (MMP-9), MMP-13, tissue inhibitor of metalloproteinase-1, nerve growth factor (NGF) and epidermal growth factor were measured by cytometric bead array technology. Release of mediators was calculated from their concentrations and the volume of tears collected over 2 min. RESULTS: Significant positive associations were found between CCL5, MMP-13 and NGF and several topographic indices. Significant negative correlations were found between IL-6 and KCI. Age-dependent associations were observed between IL-13, CXCL8, CCL5 and MMP-13 and the topographic data. CONCLUSION: Several correlations were observed between the mediators and the topographic indices, suggesting possible roles in the pathophysiology of KC. Our data indicate that some mediators have different effects on the severity of disease in an age-dependent manner.

Alterations of tear mediators in patients with keratoconus after corneal crosslinking associate with corneal changes.

Keratoconus (KC) is the most common primary corneal ectatic disease which has considerable importance in public health. Corneal collagen crosslinking (CXL) is a procedure to mitigate progression of KC and reduce demand for corneal transplantation. Although studies have proven the efficacy of CXL regarding corneal shape, none have investigated the effects of CXL on tear biomarkers which are useful tools to understand molecular mechanisms behind CXL. Our purpose was to determine the effect of CXL on tear mediators in patients with KC and analyze associations with corneal changes. Tear samples were collected pre-CXL from 26 eyes of 23 patients and during a 12-month follow-up. The mediators' concentration was measured by Cytometric Bead Array technology. Corneal topography parameters measured by Scheimpflug Camera included: Thinnest-corneal-thickness (ThCT), keratometry values (K1, K2), Radii-Minimum (Rmin), Keratoconus-Index (KI), Center-KI (CKI), Index-of-Height Asymmetry (IHA) and Index-of-Surface Variance (ISV). At baseline, KI was correlated negatively with chemokine (C-C motif) ligand 5 (CCL5) (p=0.015) and matrix metalloproteinase (MMP)-13 (p=0.007). At day 4, interleukin (IL)-6 and IL-8 increased, while IL-13, IL-17A, interferon (IFN)-γ, CCL5, MMP-13, epidermal growth factor (EGF), nerve growth factor (NGF) and plasminogen activator inhibitor (PAI-1) decreased significantly compared to pre-CXL concentrations (p≤0.02). At 6 months tissue plasminogen activator (t-PA) increased (p=0.02), while at 12 months Rmin increased (p≤0.004), and IL-6 and CXCL8 (p=0.005 and p=0.047) as well as K1, ISV and KI decreased. After 6 months CKI and ISV showed significant associations with IL-17A; CKI with IL-13 and ThCT with IL-13 (p≤0.02), while at 12 months there were reverse associations between ThCT and IL-6, IL-13, INFγ, CCL5 and PAI-1 (p≤0.02). Alterations of mediators in tear fluid after CXL associate with topographic changes highlight the fact that many mediators are involved in the complex mechanisms after CXL. Further studies on biomarkers to investigate the efficacy of CXL are needed.