Bence Lajos Kolozsvári

Assessment and reproducibility of anterior chamber depth measurement with anterior segment optical coherence tomography compared with immersion ultrasonography

PURPOSE: To measure anterior chamber depth (ACD) with an anterior segment optical coherence tomography (AS‐OCT) and a standard ultrasonic (US) axial scan (A‐scan) device using an immersion technique and to assess repeatability, reproducibility, and correlations of the measurements. SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Sixty healthy eyes of 41 patients were enrolled in a study. The central ACD was measured 5 times with AS‐OCT (Visante, Carl Zeiss Meditec) using its chamber tool and 5 times with a US A‐scan device (UltraScan Imaging System, Alcon Laboratories) using an immersion method. The measurements were performed consecutively by 2 independent observers. RESULTS: The mean ACD measured with AS‐OCT was 3.12 mm ± 0.33 (SD) by observer 1 and 3.11 ± 0.33 mm by observer 2 (P = .78). The repeatability was 0.8% ± 0.4% and 1.9% ± 1.4%, respectively. The reproducibility was 0.23%. The reliability coefficient with AS‐OCT was 99.6%. The mean ACD measured with immersion US A‐scan was 2.98 ± 0.33 mm by observer 1 and 2.95 ± 0.34 mm by observer 2 (P = .68). The repeatability was 6.4% ± 3.8% by observer 1 and 8.5% ± 4.9% by observer 2. The reproducibility was 0.88%. The reliability coefficient was 87.1% for US A‐scan measurements. The difference between ACD values with AS‐OCT and values with US A‐scan was statistically significant (P = .02). The correlation (r) between AS‐OCT and US A‐scan was 0.732 (P<.0001) by observer 1 and 0.802 (P<.0001) by observer 2. CONCLUSIONS: Anterior chamber measurements were significantly deeper with AS‐OCT than with US immersion A‐scan. Repeatability of ACD measurements was better with AS‐OCT than with immersion US, and reproducibility was equal with the 2 methods.

Anterior chamber depth measurements in phakic and pseudophakic eyes: Pentacam versus ultrasound device.

PURPOSE: To compare anterior chamber depth (ACD) measurements with a new optical device with those taken with a standard ultrasound (US) device in emmetropic phakic and pseudophakic eyes. SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Forty‐two phakic and 42 pseudophakic patients with normal axial lengths (mean 22.91 mm ± 1.21 [SD]) were enrolled in the study. The ACD was measured 3 times with Scheimpflug‐based Pentacam (Oculus) and then 3 times with a standard A‐scan US device (AL‐2000, Tomey). The data were then analyzed. RESULTS: In the phakic group, the mean ACD was 2.87 ± 0.4 mm with the Pentacam and 2.89 ± 0.49 mm with ultrasound A‐scan (US) (P = .84). In the pseudophakic group, the mean ACD was 3.41 ± 0.28 mm and 3.97 ± 0.45 mm, respectively (P<.001). The correlation between measurements was significant in both the phakic and pseudophakic groups (r = .547/P<.001 and r = .404/P = .01, respectively). CONCLUSIONS: In phakic eyes, ACD measured with the Pentacam and with US was the same. However, in pseudophakic eyes, the difference was significantly lower when the ACD was measured with the Pentacam. Therefore, in pseudophakic patients, further evaluation of ACD data with the Scheimpflug‐based system is necessary.

Keratometry evaluations with the Pentacam high resolution in comparison with the automated keratometry and conventional corneal topography

Purpose: To determine the reliability and repeatability of keratometry (K) measurements obtained with the Pentacam high resolution (HR), automated keratometry, and corneal topography systems. Methods: The right eyes of 46 healthy subjects were examined prospectively. Keratometry measurements in the flat (Kf) and steep (Ks) meridians were taken by 2 independent investigators with the Pentacam HR (Oculus, Wetzlar, Germany) followed by automated keratorefractometry (KR-8100; Topcon, Tokyo, Japan), and corneal topography (TMS-4; Tomey, Erlangen, Germany). Results: The mean K readings of the Pentacam HR, automated keratometry, and corneal topography were 43.40/43.34 diopter (D), 43.99/43.98 D, and 43.80/43.83 D, respectively. The difference between the values was statistically significant (P < 0.0001, repeated measures analysis of variance). Strong significant correlation was observed between the Pentacam HR and keratometry (Kf: r = 0.952/0.954; Ks: r = 0.845, Spearman rank test), and Pentacam HR and corneal topography (Kf: r = 0.933/0.930; Ks: r = 0.838/0.829) (P < 0.0001). No significant difference was presented between the 2 investigators for any of the instruments (P = 0.215–0.983). Moreover, high correlation was found between the K readings of the observers (interoperator intraclass correlation coefficients ranged from 0.95 to 0.99). Conclusions: The Pentacam HR provided reliable K measurements in clinical practice in comparison with an automated keratometer and a corneal topographer. Based on the results, for patient follow-up, one keratometry device is recommended.

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.

Effect of contact lens wear on the release of tear mediators in keratoconus.

Objectives: The release of different cytokines and mediators in tears of patients with keratoconus (KC) wearing contact lenses (CLs) may contribute to the pathology of KC. Methods: Cohort study was established in patients with KC wearing rigid gas permeable (RGP) CL (group I), patients with ametropia wearing silicone hydrogel (Si-Hi) CL (group II) and ametropic patients wearing RGP CL (group III). Results: Our findings indicate that before CL wear, the release of epidermal growth factor (EGF) and tissue-type plasminogen activator (t-PA) was attenuated, whereas matrix metalloproteinase (MMP)-9, interleukin (IL)-6, chemokine (C-C motif) ligand 5 (CCL5), IL-13, and plasminogen activator inhibitor (PAI)-1 were enhanced in KC compared with ametropes. An increasing linear trend over time was found for MMP-9, EGF, and CXCL8 in KC and MMP-9, MMP-13, IL-6, and CXCL8 in group III. Significant differences were observed in the linear trend over time between groups I and III for MMP-13 and tissue inhibitor of metalloproteinases (TIMP)-1; between groups I and II for MMP-9 and CXCL8; and between groups III and II for MMP-9, CXCL8, and MMP-13. In KC, the release of MMP-9 at week 6 and nerve growth factor (NGF) at 10 min was higher, but NGF at week 2 was lower than that in group II. The release of MMP-13 and NGF at week 2 and 6 were lower in the KC group as compared with group III, and similarly, with IL-6 and CXCL8 at week 2 and PAI at all time points. Conclusions: Contact lens wear can influence the levels and dynamics of various mediators in the tears of patients with KC that might have an impact on the progression of the disease.

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.

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.

Paired opposite Clear Corneal Incision: Time-Related Changes of its Effect and Factors on which those Changes Depend:

Purpose To assess astigmatism induced by paired opposite clear corneal incision (OCCI) compared to single incisions and to investigate factors on which its effect depends. Methods The study comprised 326 eyes from 326 patients. In patients with <1.0 D corneal astigmatism, clear corneal incision was performed (CC group, n = 245), and in those with >1.0 D preoperative corneal astigmatism, a second, opposite clear corneal incision was made (OCCI group, n = 81). Both groups consisted of superior, temporal, and oblique subgroups according to the steepest meridian. Prior to the surgery, and after surgery, repeated keratometry was performed and surgically induced astigmatism (SIA) was calculated using vector analysis. Results Two weeks after the surgery, the SIA was 0.67 ± 0.44 D in the CC group and 1.15 ± 0.65 D in the OCCI group; 9 weeks after the operation, it was 0.61 ± 0.43 D in the CC group and 0.99 ± 0.57 D in the OCCI group (p<0.001). The SIA showed no significant postoperative change in our groups. Conclusions Opposite clear corneal incision reliably induces about 1.0 D of corneal astigmatism on the steep meridian in proportion to the rate of preoperative astigmatism. Its magnitude is independent of the location of the incisions and its effect remains unchanged during the postoperative period.

Myopia and Late-Onset Progressive Cone Dystrophy Associate to LVAVA/MVAVA Exon 3 Interchange Haplotypes of Opsin Genes on Chromosome X

Purpose Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes). Methods A multigenerational family with X-linked high myopia and cone dystrophy was investigated. Results Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively. Conclusion Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.

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.