Alport Patients without Classic Ocular Symptoms Have Smaller Lens Diameter.

BACKGROUND The aim of this study was to present ophthalmological findings regarding Alport syndrome and report refractometry data and to present possible early signs of the syndrome. MATERIAL AND METHODS Seven patients suffering from Alport syndrome were referred to the Department of Ophthalmology at the University of Debrecen between January 1st, 2014, and December 31st, 2015. All patients underwent slit lamp evaluation and dilated fundus biomicroscopy, with special attention paid to lenticonus and retinal changes. IOL Master, Pentacam HR, and ultrasound biomicroscopy were performed to assess keratometry, corneal thickness, anterior chamber depth, lens size, and axial length data. RESULTS One patient out of seven had ocular symptoms. Posterior polymorphous corneal dystrophy (PPMD) and dot-and-fleck retinopathy were seen. Meanwhile, although keratoconus was not proven, remarkable astigmatism with high myopia was detected. The other six patients were found to have a significantly smaller lens diameter (an average of 7.82±0.66 mm, p=0.035) compared to normal controls (an average of 8.65±0.46 mm). Lenses also tended to be thicker in Alport patients (3.48±0.19 mm) compared to controls (3.4±0.2 mm), although the difference was not significant (p=0.394). The power of the lens also showed a significant difference (p=0.026), with Alport patients having lower lens power. CONCLUSIONS Alport syndrome patients without classical ophthalmological findings have smaller crystalline lens diameter and lower lens power. These signs may support the diagnosis of Alport syndrome. Ophthalmologists should not only seek for the known classic signs, but also the parameters of the crystalline lens, especially if genetic testing is not available.

Treat-and-Extend versus Monthly Regimen in Neovascular Age-Related Macular Degeneration: Results with Ranibizumab from the TREND Study.

PURPOSE: To evaluate the efficacy and safety of ranibizumab 0.5 mg treat-and-extend (T&E) versus monthly regimens in patients with neovascular age-related macular degeneration (nAMD) from the TReat and extEND (TREND) study. DESIGN: A 12-month phase 3b visual acuity (VA) assessor-masked, multicenter, randomized, interventional study. PARTICIPANTS: Six hundred fifty patients. METHODS: Treatment-naïve nAMD patients (age, ≥50 years) were randomized 1:1 to receive either a ranibizumab 0.5 mg T&E (n = 323) or monthly (n = 327) regimen. MAIN OUTCOMES MEASURES: The primary objective was to show noninferiority of ranibizumab 0.5 mg T&E versus monthly regimen, as assessed by the change in best-corrected VA (BCVA) from baseline to the end of the study. Secondary objectives included change in retinal central subfield thickness (CSFT) from baseline to the end of study, treatment exposure, and safety. RESULTS: Overall, 89.8% (T&E) and 90.2% (monthly) of patients completed the study. Patient demographic and baseline characteristics were well balanced between the 2 treatment groups. The T&E regimen was noninferior (P < 0.001) to the monthly regimen, with a least squares mean BCVA change from baseline of 6.2 versus 8.1 letters to the end of study, respectively. In both treatment groups, most BCVA improvements occurred during the first 6 months and were maintained until the end of the study. The mean change in CSFT from baseline to the end of study was -169.2 µm and -173.3 µm in the T&E and monthly groups, respectively. Fewer injections were required in patients receiving the T&E (8.7) versus monthly (11.1) regimen, with mean number of postbaseline visits of 8.9 and 11.2, respectively. Types and rates of adverse events were comparable between the treatment groups. CONCLUSIONS: Ranibizumab 0.5 mg administered according to a T&E regimen was statistically noninferior and clinically comparable with a monthly regimen in improving VA from baseline to the end of study. No new safety signals for ranibizumab were identified.

[New international consensus statement about the definition, classification, ethiology, diagnostics and therapy of dry eye (TFOS DEWS II)]. / Új nemzetközi konszenzusnyilatkozat a száraz szem definíciójáról, felosztásáról, etiológiájáról, diagnosztikájáról és terápiájáról.

Ten years have passed since the publication of the DEWS Report that summarized the information based on scientific literature concerning dry eye disease. Hundreds of papers have been published since then and time has come for a new summary. Organized by the Tear Film & Ocular Surface Society, 12 working groups summerized former and recent data. The DEWS II Report was created. The authors of the present publication summarize the most important changes in definition, classification, diagnostics, and therapy concerning dry eye disease. They also disclose the relevant changes on which the non-ophthalmologist specialists have to be informed. The DEWS II Report published by TFOS consists of 11 chapters. Completely new chapters deal with the role of sensation/pain and iatrogenic dry eyes. Orv Hetil. 2018; 159(20): 775-785.

[Femtosecond laser-assisted keratoplasty]. / Femtoszekundumlézeres keratoplasztika.

INTRODUCTION AND AIM: To present our results on femtosecond laser-assisted penetrating keratoplasty. PATIENTS AND METHOD: Twenty-five eyes of 25 patients underwent surgery with the following indications: pseudophakic bullous keratopathy (n = 10), keratoconus (n = 4), corneal dystrophy (n = 5), corneal scar (n = 4), band keratopathy (n = 2). Trephination of both the donor and recipient corneas were performed with VisuMax femtosecond laser device (Carl Zeiss Meditec AG, Jena, Germany). In each case, trephinaton of the donor tissue was performed first with an artificial anterior chamber (Moria, Antony, France). For the surgical plan and in the postoperative period we obtained different corneal imaging modalities. The corneal power was measured with corneal topography (TMS-4, Tomey, Nürnberg, Germany) and Scheimpflug tomography (Pentacam HR, Oculus, Wetzlar, Germany). The central corneal thickness was evaluated with Pentacam and corneal endothelial cell density was measured with specular microscopy (SP3000P, Topcon, Tokyo, Japan). The corneal structure was imaged with anterior segment optical coherence tomography (Visante, Carl Zeiss Meditec AG). All measurements were performed every 3 months in the first year and yearly thereafter. The follow-up period was 3 years in every case. RESULTS: The corrected decimal visual acuity showed an improvement from a preoperative 0.1 ± 0.1 to a postoperative 0.71 ± 0.18 value at the end of the follow-up period (p = 0.03). All corneal grafts maintained their transparency, there were no immunological rejection during the follow-up. Topographical astigmatism was 4.5 ± 3.1 D in the first month; it showed a decreasing tendency, but there was no significant change in the 3-year period. The mean central corneal thickness changed with 60 µm during the follow-up; there was no significant difference between the first month (564 ± 52 µm) and the third year (596 ± 64 µm) mean pachymetry values (p = 0.1). The mean endothelial cell density decreased first, then remained stable, but did not change significantly from the first (1641 ± 433 cells/mm2) to the last postoperative visit (1220 ± 391 cells/mm2, p = 0.1). CONCLUSIONS: In the case of femtosecond laser-assisted penetrating keratoplasty, trephination of the donor and recipient cornea is performed automatically in a highly precise fashion. The accurate cutting surface provides excellent wound apposition and healing. Both anatomical and functional rehabilitation of patients undergoing surgery are favourable and fast. Orv Hetil. 2018; 159(17): 671-676.

Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene.

PURPOSE: NEUROD1 is a tissue-specific basic helix loop helix (bHLH) protein involved in the development and maintenance of the endocrine pancreas and neuronal elements. Loss of NEUROD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. Heterozygous loss-of-function mutations in NEUROD1 have previously been described as a cause of maturity-onset diabetes of the young (MODY) and late-onset diabetes. To date, homozygous loss-of-function NEUROD1 mutations have only been detected in two patients. Both mutations caused permanent neonatal diabetes and severe neurologic defects, including visual impairment. However, a detailed ophthalmological phenotype of this novel syndrome has not yet been reported. Our aim was to characterize the ophthalmological phenotype associated with the previously reported homozygous c.427_428CT mutation in the NEUROD1 gene. METHODS: The female patient was investigated on multiple occasions between 2009 (age 14) and 2014 (age 19), including visual acuity testing, automated perimetry, funduscopy, anterior-segment imaging, optical coherence tomography of the posterior pole, standard full-field electroretinography, and fundus-autofluorescence imaging. RESULTS: The patient had nyctalopia, blurry vision, and visual field constriction from early childhood. Her best corrected visual acuity ranged between 20/25 and 15/25 during the investigation period. Perimetry showed concentric constriction of the visual field, sparing only the central 30 degrees in both eyes. The anterior segment did not show any morphological changes. Optical coherence tomography revealed total absence of the photoreceptor layer of the retina outside the fovea, where a discoid remnant of cone photoreceptors could be detected. Neither setting of the standard full-field electroretinography could detect any electrical response from the retina. Color fundus photos presented peripheral chorioretinal atrophy and central RPE mottling. A hyperreflective parafoveal ring was detected on fundus autofluorescent photos, a characteristic sign of hereditary retinal dystrophies. CONCLUSIONS: To the best of our knowledge, this is the first report on the ophthalmological phenotype associating with a homozygous NEUROD1 null mutation in humans. Our results indicate that the loss of NEUROD1 has similar functional and anatomic consequences in the human retina as those described in mice. The present description can help the diagnosis of future cases and provide clues on the rate of disease progression.

Repeatability data and agreement of keratometry with the VERION system compared to the IOLMaster.

PURPOSE: To analyze the repeatability of keratometric and white-to-white (WTW) distance measurements with the VERION Measurement Module (Alcon Laboratories, Inc., Fort Worth, TX) and to compare the measured data to the results of the IOLMaster (Carl Zeiss Meditec, Jena, Germany). METHODS: Three images were captured with the VERION and the flattest and steepest keratometric data, the astigmatism axis, and the WTW distance were recorded. Subsequently, the axial length, the keratometric data with axis, and the WTW distance were measured with an IOLMaster. The repeatability data of the keratometric value of the VERION System, converted to cross cylinder J0 and J45 vector components, were analyzed. The agreement data for keratometry obtained by the VERION System and the differences regarding keratometric data and WTW distance compared to IOLMaster were calculated. RESULTS: The measurements were conducted in 50 eyes of 50 healthy volunteers (median age: 50.32 years, range: 19.34 to 85.3 years). The flattest and the steepest keratometric data, the diopter of astigmatism, the J0 and J45 vector components, and WTW distance did not differ significantly between devices (P > .05). Intraclass correlation coefficients (range: 0.863 to 0.994) and Cronbach's alpha values (range: 0.950 to 0.998) were high for all parameters measured by the VERION System. CONCLUSIONS: The VERION System has high repeatability and agreement with the IOLMaster, making it suitable as an alternative tool in clinical practice.

Vascular Endothelial Growth Factor in Tear Samples of Patients with Systemic Sclerosis.

BACKGROUND: Systemic sclerosis is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. Changes in levels of proangiogenic cytokines had already been determined largely in serum. Our aim was to assess the levels of VEGF in human tears of patients with SSC. PATIENTS AND METHODS: Forty-three patients (40 female and 3 men, mean (SD) age 61 (48-74) years) with SSc and 27 healthy controls were enrolled in this study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples. RESULTS: The average collected tear fluid volume developed 10.4 µL (1.6-31.2) in patients and 15.63 µL (3.68-34.5) in control subjects. The average total protein level was 6.9 µg/µL (1.8-12.3) in tears of patients and control tears contained an average of 4.132 µg/µL (0.1-14.1) protein. In patients with SSc the average concentration of VEGF was 4.9 pg/µL (3.5-8.1) and 6.15 pg/µL (3.84-12.3) in healthy samples. CONCLUSIONS: Total protein production was increased because of the smaller tear volume. Decreased VEGF in tear of SSc patients can be explained also by the decreased tear secretion of patients.

Analysis of surgically induced astigmatism on the posterior surface of the cornea.

PURPOSE: To measure surgically induced astigmatism (SIA) on the posterior surface of the cornea using Scheimpflug-based keratometry on eyes with with-the-rule astigmatism. METHODS: Repeated Scheimpflug-based keratometry was obtained preoperatively and a mean of 8.65 weeks postoperatively following superior clear corneal incisions. Differences in the keratometric values and SIA were determined on the anterior and posterior surfaces separately and the data were analyzed. RESULTS: The study included 88 eyes of 88 patients (age range: 46.4 to 87.5 years), with the steepest total corneal meridian between 75° and 105°. Preoperatively, the magnitude of the anterior and posterior corneal astigmatism was 0.74 ± 0.44 and 0.29 ± 0.14 diopters (D), respectively, which was greater than 0.5 D in 10 eyes (11.36%). The difference between preoperative and postoperative keratometric data on the posterior surface was significant, as was the difference between the preoperative and postoperative posterior astigmatism. The mean magnitude of posterior corneal SIA was 0.32 ± 0.29 D, which was 0.5 D or greater in 22 eyes (25.00%). A statistically significant correlation was observed between the diopter of the preoperatively measured posterior corneal astigmatism and the postoperative SIA on the posterior surface (r = 0.34, P = .001). The correlation was not significant between SIA on the anterior and posterior surfaces (r = 0.10, P = .36). CONCLUSIONS: SIA on the posterior surface of the cornea may have a significant role, especially in cases of toric intraocular lens implantation. Posterior corneal astigmatism and SIA may have a significant clinical impact on more precise planning of cataract surgeries.

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.

Three novel germ-line VHL mutations in Hungarian von Hippel-Lindau patients, including a nonsense mutation in a fifteen-year-old boy with renal cell carcinoma.

BACKGROUND: Von Hippel-Lindau disease is an autosomal dominantly inherited highly penetrant tumor syndrome predisposing to retinal and central nervous system hemangioblastomas, renal cell carcinoma and phaeochromocytoma among other less frequent complications. METHODS: Molecular genetic testing of the VHL gene was performed in five unrelated families affetced with type I VHL disease, including seven patients and their available family members. RESULTS: Molecular genetic investigations detected three novel (c.163 G > T, c.232A > T and c.555C > A causing p.Glu55X, p.Asn78Tyr and p.Tyr185X protein changes, respectively) and two previously described (c.340 + 1 G > A and c.583C > T, resulting in p.Gly114AspfsX6 and p.195GlnX protein changes, respectively) germline point mutations in the VHL gene. Molecular modeling of the VHL-ElonginC-HIF-1alpha complex predicted that the p.Asn78Tyr amino acid exchange remarkably alters the 77-83 loop structure of VHL protein and destabilizes the VHL-HIF-1alpha complex suggesting that the mutation causes type I phenotype and has high risk to associate to renal cell carcinoma. The novel p.55X nonsense mutation associated to bilateral RCC and retinal angioma in a 15-year-old male patient. CONCLUSION: We describe the earliest onset renal cell carcinoma in VHL disease reported so far in a 15-year-old boy with a nonsense VHL mutation. Individual tailoring of screening schedule based on molecular genetic status should be considered in order to diagnose serious complications as early as possible. Our observations add to the understanding of genotype-phenotype correlation in VHL disease and can be useful for genetic counseling and follow-up of VHL patients.

Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study.

OBJECTIVE: To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME). DESIGN: Twenty-four-month, open-label, multicenter, Phase IIIb extension study. PARTICIPANTS: Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension. METHODS: All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension. MAIN OUTCOME MEASURES: Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA. RESULTS: Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 µm, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 µm, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 µm, and 4.3, respectively), with an average of 4.1 ranibizumab injections. CONCLUSIONS: Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Analysis of age-dependence of the anterior and posterior cornea with scheimpflug imaging.

PURPOSE: To assess keratometric and higher-order aberrations of the anterior and posterior cornea and their age-related changes. METHODS: This study investigated one healthy eye of 227 patients (mean age: 55.15 ± 21.2 years; range: 16 to 90 years; 135 right eyes, 92 left eyes). Images were captured from each eye with Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany) using automatic mode. Keratometric, astigmatism data, and corneal higher-order aberrations were analyzed. RESULTS: With respect to laterality, no deviance was found in any of the parameters (P > .05). Mean refractive error was 0.52 ± 0.23 diopters. The level of astigmatism decreased significantly with advancing age for both the anterior and posterior corneal surfaces (P < .05). The overall root mean square of the higher-order aberration increased continuously with age (r = 0.517; P < .01), which can be explained by the combined effect of the increased in both the anterior and posterior corneal root mean square higher-order aberrations. Of the higher-order aberrations, the constant increase of the primary and secondary spherical aberration with aging (P < .01) is caused by the spherical aberration growth of the anterior surface. Apart from these, only the vertical coma aberration of the posterior surface and the vertical trefoil aberrations of both the anterior and posterior surfaces showed a significantly positive correlation with aging (P < .05). CONCLUSIONS: Corneal astigmatism showed a significant decrease with aging. Of the higher-order aberrations, primary and secondary spherical aberrations, vertical coma, and vertical trefoil significantly increase with age, whereas other higher-order aberrations show no correlation with aging.

Repeatability of ocular biomechanical data measurements with a Scheimpflug-based noncontact device on normal corneas.

PURPOSE: To analyze the repeatability of a new device measuring ocular biomechanical properties, central corneal thickness (CCT), and intraocular pressure (IOP) and to investigate these parameters and their correlations in healthy eyes. METHODS: Three consecutive measurements were performed on each eye using the CorVis ST device (Oculus Optikgeräte, Inc., Wetzler, Germany). Ten specific parameters, CCT, and IOP were measured. Biometric data were recorded with IOLMaster (Carl Zeiss Meditec, Jena, Germany). RESULTS: This study comprised 75 eyes of 75 healthy volunteers (mean age: 61.24 ± 15.72 years). Mean IOP was 15.02 ± 2.90 mm Hg and mean CCT was 556.33 ± 33.13 µm. Intraclass correlation coefficient (ICC) was 0.865 for IOP and 0.970 for CCT, and coefficient of variation was 0.069 for IOP and 0.008 for CCT. ICC was 0.758 for maximum amplitude at highest concavity and 0.784 for first applanation time, and less than 0.6 for all other parameters. The device-specific data showed no significant relationship with age and axial length. Flattest and steepest keratometric values and IOP showed a significant correlation with the 10 device-specific parameters. CONCLUSIONS: The CorVis ST showed high repeatability for only IOP and pachymetric values. Single measurements are not reliable for the 10 device-specific parameters. The device allows for conducting clinical examinations and screening for surgeries altering ocular biomechanical properties with some form of averaging of multiple measurements.

Increased level of platelet P-selectin in nonarteritic anterior ischemic optic neuropathy.

PURPOSE: P-selectin receptor is expressed in platelets and endothelial cells in a cell-activation-dependent manner. Platelet P-selectin (CD62) levels may become elevated in a number of vasoocclusive diseases, including arteriosclerosis, atherothrombosis, and diabetes mellitus (DM). Nonarteritic anterior ischemic optic neuropathy (NAION) is associated with a sudden loss of vision due to the vascular insufficiency of ciliary arteries supplying the optic nerve. In this study, our aim was to investigate the presence of increased platelet reactivity in the development of NAION. METHODS: Twenty-one NAION patients, 39 healthy control subjects, and 44 patients suffering from diabetes mellitus (DM) were examined in our case-control, pilot study. Platelet activation was investigated by flow cytometric analysis of the mean fluorescence intensity (MFI) of CD62 on platelets. These results were compared among the different study groups. RESULTS: NAION patients showed considerably although not significantly (p = 0.2017) higher P-selectin MFI values (71.98 ± 40.30) versus healthy subjects (55.48 ± 20.95), insulin-dependent DM patients (50.02 ± 13.08), and non-insulin-dependent DM subjects (54.72 ± 24.74). However, logistic regression analysis resulted in a statistically significant adjusted effect on the odds of NAION when CD62 MFI values were logarithmically transformed (OR: 3.86, 95 % CI: 1.10 to 13.53, p = 0.0346). CONCLUSION: Elevated platelet CD62 positivity may be related to NAION, suggesting a possible role of enlarged platelet activity in the generation of this type of ischemic optic neuropathy.

Tear fluid proteomics multimarkers for diabetic retinopathy screening.

BACKGROUND: The aim of the project was to develop a novel method for diabetic retinopathy screening based on the examination of tear fluid biomarker changes. In order to evaluate the usability of protein biomarkers for pre-screening purposes several different approaches were used, including machine learning algorithms. METHODS: All persons involved in the study had diabetes. Diabetic retinopathy (DR) was diagnosed by capturing 7-field fundus images, evaluated by two independent ophthalmologists. 165 eyes were examined (from 119 patients), 55 were diagnosed healthy and 110 images showed signs of DR. Tear samples were taken from all eyes and state-of-the-art nano-HPLC coupled ESI-MS/MS mass spectrometry protein identification was performed on all samples. Applicability of protein biomarkers was evaluated by six different optimally parameterized machine learning algorithms: Support Vector Machine, Recursive Partitioning, Random Forest, Naive Bayes, Logistic Regression, K-Nearest Neighbor. RESULTS: Out of the six investigated machine learning algorithms the result of Recursive Partitioning proved to be the most accurate. The performance of the system realizing the above algorithm reached 74% sensitivity and 48% specificity. CONCLUSIONS: Protein biomarkers selected and classified with machine learning algorithms alone are at present not recommended for screening purposes because of low specificity and sensitivity values. This tool can be potentially used to improve the results of image processing methods as a complementary tool in automatic or semiautomatic systems.

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.

Optical coherence tomography for biofilm detection in chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease that seems to be associated with the presence of microbial biofilms and corresponding subepithelial inflammatory reactions. Optical coherence tomography (OCT) might be applied to detect bacterial and fungal biofilms in patients with CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of six patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27 patients (81.5 %) with CRSwNP and in none of six negative controls. In our series, OCT scan showed an obvious association with the findings of H.E. and Gram staining and was allocated to be a good predictor of biofilm existence. On OCT images, biofilms were displayed as distinct superficial layers with high optical density. It was found that microscopic architecture of biofilms was strongly associated with the integrity of nasal mucosa and to the cellular pattern of subepithelial inflammatory reaction. This study confirmed the presence of microbial biofilms in patients with CRSwNP according to OCT scans and histological analysis. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected preoperatively. In conclusion, single application of OCT analysis or combination with conventional histological protocols provides a robust and reliable method for the detection of bacterial and fungal biofilms in CRSwNP. Level of evidence 3b, individual case-control study.

[Contact lens-related keratitis]. / A kontaktlencse-viselés következtében kialakuló keratitisekrol.

Nowadays, keratitis, corneal infection due to wearing contact lens means an increasingly serious problem. Neglected cases may lead to corneal damage that can cause blindness in cases of otherwise healthy eyes. Early diagnosis based on the clinical picture and the typical patient history is an important way of prevention. Prophylaxis is substantial to avoid bacterial and viral infection that is highly essential in this group of diseases. Teaching contact lens wearers the proper contact lens care, storage, sterility, and hygiene regulations is of great importance. In case of corneal inflammation early accurate diagnosis supported by microbiological culture from contact lenses, storage boxes or cornea is very useful. Thereafter, targeted drug therapy or in therapy-resistant cases surgical treatment may even be necessary in order to sustain suitable visual acuity.

Fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 are strongly expressed in the epithelium of human granular and lattice type I corneal dystrophies.

PURPOSE: To determine the extracellular matrix proteins involved in the formation of human granular and lattice type I corneal stromal dystrophies, the expression patterns of fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 were compared in human corneal stromal dystrophy samples. METHODS: Ten cases of granular dystrophy, 7 cases of lattice dystrophy, and 6 normal corneal buttons collected during corneal transplantation were examined for their expression patterns of fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 by immunohistochemistry. RESULTS: Highly elevated fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 were observed in the epithelial layer of both granular and lattice type I dystrophies. Fibrillin-2, tenascin-C, and matrilin-4 in the granular dystrophy and all antibodies in the lattice dystrophy showed statistically significant staining in the corneal stroma (p<0.05). Interestingly, fibrillin-2, matrilin-2, and matrilin-4 stained significantly in amyloid plaques of lattice type 1 dystrophy. CONCLUSIONS: Fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 may be markers of the pathogenesis of either granular or lattice type I corneal dystrophy, as revealed by immunohistochemical analysis. Each molecule seems to be involved in the regeneration and reorganization of the corneal matrix in granular and lattice type I dystrophies.

Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy.

In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial - and NSC-associated markers both after direct fixation and repetitive passages. In conclusion, the adult human eye may harbor two different populations of neuroepithelial stem/progenitor cells; a non-glial population located in the proximal pars plana around peripheral cysts in addition to a population with Müller glia characteristics. Yet, we only found that the glial population was able to respond to retinal injury by targeted migration into the vitreous.