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.

Longitudinal Changes in Corneal Cell and Nerve Fiber Morphology in Young Patients with Type 1 Diabetes with and without Diabetic Retinopathy: A 2-Year Follow-up Study.

Purpose: We have previously used in vivo corneal confocal microscopy (IVCCM) to demonstrate significant alterations in the corneal epithelial cells, stromal keratocytes, and subbasal nerves in young patients with type 1 diabetes mellitis (T1DM), especially those with diabetic retinopathy (DR). We have evaluated the change in corneal cellular and subbasal nerve morphology over 2 years in young patients with T1DM with or without DR. Methods: A total of 19 patients with T1DM, without (n = 12) and with (n = 7) DR and 19 age- and sex-matched healthy control subjects underwent quantification of corneal cellular and subbasal nerve plexus morphology by using IVCCM at baseline and after 2 years. Results: There was no significant change in corneal basal epithelial, posterior stromal keratocyte, or endothelial cell densities over 2 years. However, there was a significant reduction in corneal nerve branch (P = 0.03) and total nerve branch density (P = 0.04) in patients without DR and a significant reduction in corneal nerve fibre density (P = 0.004) in those with DR. Conclusions: IVCCM can detect a progressive loss of corneal nerve fibers in young patients with T1DM and may allow the identification of individuals at risk of neuropathy progression for more active risk factor reduction.

[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.

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.

Plasminogen activator activity in tears of pregnant women.

PURPOSE: Plasminogen activator activity (PAA) in tears of pregnant women was investigated at various gestation times to assess the availability of plasminogen activator for aiding potential corneal wound healing processes during pregnancy. METHODS: PAA was measured by a spectrophotometric method. The analysis used 91 tear samples from pregnant and non-pregnant women, supplemented with 10 additional tear PAA measurements from non-pregnant women obtained in a previous study. RESULTS: Tear levels of PAA in pregnant women formed a bimodal distribution. Either the tear PAA level was zero or non-zero during pregnancy. When non-zero, the tear PAA level was dissociated from gestation time and not different than non-pregnant and post-pregnant levels. The frequency of occurrence of zero level tear PAA increased with gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women in the first, second and third trimester, respectively. CONCLUSIONS: Overall, of the tear samples taken from women during pregnancy, a total of 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAA values throughout gestation equivalent to non-pregnant tear PAA values, suggesting local control of the source of PAA in tears. Given the importance of the plasminogen activator system in tears to wound healing in the cornea, and the high occurrence of zero tear PAA in our sample of pregnant women, elective corneal surgery would be contraindicated. If corneal surgery is nevertheless necessary, the tear PAA level would be worth checking and patients with low level should be closely observed 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 image-based changes in anterior segment parameters during accommodation induced by short-term reading.

PURPOSE: To analyze the effect of the accommodation on the anterior segment data (corneal and anterior chamber parameters) induced by short-time reading in a healthy, nonpresbyopic adult patient group. METHODS: Images of both eyes of nonpresbyopic volunteers were captured with a Scheimpflug device (Pentacam HR) in a nonaccommodative state. Fifteen minutes of reading followed and through fixation of the built-in target of Pentacam HR further accommodation was achieved and new images were captured by the device. Anterior segment parameters were observed and the differences were analyzed. RESULTS: Fifty-two healthy eyes of 26 subjects (range 20.04-28.58 years) were analyzed. No significant differences were observed in the keratometric values before and after the accommodative task (p = 0.35). A statistically significant difference was measured in the 5.0-mm-diameter and the 7.0-mm-diameter corneal volume (p = 0.01 and p = 0.03) between accommodation states. Corneal aberrometric data did not change significantly during short-term accommodation. Significant differences were observed between nonaccommodative and accommodative states of the eyes for all measured anterior chamber parameters. CONCLUSIONS: Among the parameters of the cornea, only corneal volume changed during the short-term accommodation process, showing some fine changes with accommodation of the cornea in young, emmetropic patients. The position of the pupil and the anterior chamber parameters were observed to change with accommodation as captured by a Scheimpflug device.

Analysis of optic disc damage by optical coherence tomography in terms of therapy in non-arteritic anterior ischemic optic neuropathy.

This study aimed to assess the relationship between the rate of nerve fiber loss in non-arteritic anterior ischemic optic neuropathy (NAION) and time delay before therapy. Total 24 patients received the same treatment within or after 2wk (early and late groups). There were significantly lower level of destruction of nerve fibers (P=0.0014) and significantly better visual field sensitivity (P=0.039) in early group. The results indicate that therapy should be started within 2wk. The degree of ischemic damage due to NAION correlates well with retinal nerve fiber layer thickness and the ischemia-induced decrease in visual field sensitivity.

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.

Ocular biomechanical measurements on post-keratoplasty corneas using a Scheimpflug-based noncontact device.

AIM: To analyse ocular biomechanical properties, central corneal thickness (CCT) and intraocular pressure (IOP) in post-keratoplasty eyes, as compared to normal subjects, with a new Scheimpflug-based technology. Moreover, biomechanical data were correlated with the size and age of the donor and recipient corneas. METHODS: Measurements were conducted on 46 eyes of 46 healthy patients without any corneal pathology (age: 53.83±20.8y) and 30 eyes of 28 patients after penetrating keratoplasty (age: 49.43±21.34y). Ten biomechanical parameters, the CCT and IOP were recorded by corneal visualization scheimpflug technology (CorVis ST) using high-speed Scheimpflug imaging. Keratometry values were also recorded using Pentacam HR system. Scheimpflug measurements were performed after 43.41±40.17mo (range: 11-128mo) after the keratoplasty and after 7.64±2.34mo (range: 5-14mo) of suture removal. RESULTS: Regarding the device-specific biomechanical parameters, the highest concavity time and radius values showed a significant decrease between these two groups (P=0.01 and P<0.001). None of other biomechanical parameters disclosed a significant difference. The CCT showed a significant difference between post-keratoplasty eyes as compared to normal subjects (P=0.003) using the CorVis ST device. The IOP was within the normal range in both groups (P=0.84). There were no significant relationships between the keratometric data, the size of the donor and recipient, age of the donor and recipient and biomechanical properties obtained by CorVis ST. CONCLUSION: The ocular biomechanics remain stable after penetrating keratoplasty according to the CorVis ST measurements. Only two from the ten device-specific parameters have importance in the follow-up period after penetrating keratoplasty.

Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy.

PURPOSE: The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. METHODS: A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). RESULTS: We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. CONCLUSIONS: Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

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.

Presence of Fleischer ring and prominent corneal nerves in keratoconus relatives and normal controls.

AIM: To examine the occurrence of commonly known clinical signs of keratoconus (KC), i.e. Fleischer ring, prominent corneal nerves and thinning, among unaffected family members of KC patients and healthy control individuals. METHODS: Data of both eyes of 117 relatives of KC patients having no manifest disease based on videokeratography indices (KC relatives), and 142 controls were used for Pearson correlation and t-test statistics. Correlation of Fleischer ring, prominent corneal nerves and central pachymetry data were tested with each other and with videokeratography indices (KSI, KISA, 3 and 6 mm Fourier asymmetry, and I-S). RESULTS: A moderate correlation was found between Fleischer ring and all examined topographical indices. Most important correlation was present with 6 mm Fourier asymmetry, and corneal pachymetry (r=0.272, P<0.001; r=-0.234, P=0.027, respectively). Similar correlations were found with prominent corneal nerves (r=0.234, P<0.001 for 6 mm Fourier asymmetry and r=-0.235, P=0.0265 for pachymetry). KC family members who exhibited Fleischer ring or prominent nerves had thinner and more asymmetric corneas than those without Fleischer ring or prominent corneal nerves (P<0.05 for pachymetry and topographic indices with t-test and Mann-Whitney rank sum test). Though rarely, Fleischer ring and prominent corneal nerves occurred among normal controls, indicating the existence of forme fruste cases in the normal population. Control subjects, who had corneal Fleischer ring or prominent nerves had corneas more similar to KC than other controls (t-test: increased KSI and KISA, P=0.048 and 0.012, respectively). CONCLUSION: In KC family members and healthy individuals, Fleischer ring and prominent corneal nerves are associated with features of KC and may suggest a possibility of forme fruste KC. Searching for the possible presence of Fleischer ring or prominent nerves on the cornea may help in the decision whether or not to diagnose subclinical KC in a borderline case.

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.

Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers.

Background. It is estimated that 347 million people suffer from diabetes mellitus (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The progression of DR can be slowed down with early diagnosis and treatment. Therefore our aim was to develop a novel automated method for DR screening. Methods. 52 patients with diabetes mellitus were enrolled into the project. Of all patients, 39 had signs of DR. Digital retina images and tear fluid samples were taken from each eye. The results from the tear fluid proteomics analysis and from digital microaneurysm (MA) detection on fundus images were used as the input of a machine learning system. Results. MA detection method alone resulted in 0.84 sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87 sensitivity and 0.68 specificity values were achieved. The combined data analysis integrated the features of the proteomics data along with the number of detected MAs in the associated image and achieved sensitivity/specificity values of 0.93/0.78. Conclusions. As the two different types of data represent independent and complementary information on the outcome, the combined model resulted in a reliable screening method that is comparable to the requirements of DR screening programs applied in clinical routine.

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.

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.

A novel proteotoxic stress associated mechanism for macular corneal dystrophy.

Macular corneal dystrophy is a rare autosomal recessive eye disease affecting primarily the corneal stroma. Abnormal accumulation of proteoglycan aggregates has been observed intra- and extracellularly in the stromal layer. In addition to the stromal keratocytes and corneal lamellae, deposits are also present in the basal epithelial cells, endothelial cells and Descemet's membrane. Misfolding of proteins has a tendency to gather into aggregating deposits. We studied interaction of molecular chaperones and proteasomal clearance in macular dystrophy human samples and in human corneal HCE-2 epithelial cells. Seven cases of macular corneal dystrophy and four normal corneal buttons collected during corneal transplantation were examined for their expression patterns of heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62. In response to proteasome inhibition the same proteins were analyzed by western blotting. Slit-lamp examination, in vivo confocal cornea microscopy and transmission electron microscopy were used for morphological analyses. Heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62 were upregulated in both the basal corneal epithelial cells and the stromal keratocytes in macular corneal dystrophy samples that coincided with an increased expression of the same molecules under proteasome inhibition in the HCE-2 cells in vitro. We propose a novel regulatory mechanism that connects the molecular chaperone and proteasomal clearance system in the pathogenesis of macular corneal dystrophy.

Effects of awakening and the use of topical dexamethasone and levofloxacin on the cytokine levels in tears following corneal transplantation.

OBJECTIVES: To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. METHODS: Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. RESULTS: At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. CONCLUSIONS: Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.