Analysis of the ocular surface functional unit in episodic migraine.

AIM: Migraine is a chronic neurovascular disease that affects the trigeminovascular system. The purpose of this study was to evaluate corneal subbasal nerve fibers, dendritic cells and to measure tear film parameters in migraine. PATIENTS AND METHODS: 87 eyes of 44 patients suffering from migraine with a mean age of 33.23 ± 11.41 years were included in our study. 25 age-matched controls (mean age of 30.16 ± 12.59 years; P = 0.162) were recruited. The corneal subbasal plexus and the dendritic cells (DC) were analyzed using in vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module; Heidelberg Engineering GmbH), and the tear film was imaged using LacryDiag (Quantel Medical, France). RESULTS: Regarding the subbasal nerve fibers of the cornea, none of the examined parameters differed significantly in migraine patients from controls. We found a significant increase in the corneal DC density (P < 0.0001) and DC area (P < 0.0001) in migraine patients compared to healthy volunteers. DC density showed a positive correlation with the monthly attack frequency (r = 0.32, P = 0.041) and the DC area a negative correlation with corneal nerve branch density (r = -0.233, P = 0.039), nerve fiber length (r = -0.232, P = 0.04) and total branch density (r = -0.233, P = 0.039). Using LacryDiag a significant loss of Meibomian gland area could be detected on the superior eyelid (P = 0.005) in migraine. CONCLUSIONS: Our results suggest the presence of neuroinflammation in the cornea of migraine patients affecting the peripheral trigeminal system. Dendritic cells surrounding the subbasal plexus may be involved in the activation and modulation of pain in migraine.

Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them.

An imbalance of homeostasis in the retina leads to neuron loss and this eventually results in a deterioration of vision. If the stress threshold is exceeded, different protective/survival mechanisms are activated. Numerous key molecular actors contribute to prevalent metabolically induced retinal diseases-the three major challenges are age-related alterations, diabetic retinopathy and glaucoma. These diseases have complex dysregulation of glucose-, lipid-, amino acid or purine metabolism. In this review, we summarize current knowledge on possible ways of preventing or circumventing retinal degeneration by available methods. We intend to provide a unified background, common prevention and treatment rationale for these disorders and identify the mechanisms through which these actions protect the retina. We suggest a role for herbal medicines, internal neuroprotective substances and synthetic drugs targeting four processes: parainflammation and/or glial cell activation, ischemia and related reactive oxygen species and vascular endothelial growth factor accumulation, apoptosis and/or autophagy of nerve cells and an elevation of ocular perfusion pressure and/or intraocular pressure. We conclude that in order to achieve substantial preventive or therapeutic effects, at least two of the mentioned pathways should be targeted synergistically. A repositioning of some drugs is considered to use them for the cure of the other related conditions.

Protective Effects of Pituitary Adenylate-Cyclase-Activating Polypeptide on Retinal Vasculature and Molecular Responses in a Rat Model of Moderate Glaucoma.

Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model.

Analysis of microvascular and neurodegenerative complications of mild COVID-19.

PURPOSE: To examine retinal and corneal neurodegenerative and retinal microvascular changes in patients after mild or asymptomatic COVID-19 disease compared to age-matched controls. METHODS: Thirty-five (35) patients after PCR-proven SARS-CoV-2 infection and 28 age-matched controls were enrolled. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal subbasal nerve plexus was quantified. Vessel density for superficial (SCP) and deep capillary plexus (DCP) and structural OCT parameters were recorded. RESULTS: Significantly lower nerve branch density (P = 0.0004), nerve fiber area (P = 0.0001), nerve fiber density (P = 0.0009), nerve fiber length (P < 0.0001), and total nerve branch density (P = 0.002) values were observed in patients after COVID-19 compared to healthy controls. VD of the temporal SCP was significantly different between the two groups (P = 0.019). No other SCP and DCP vessel density parameter differed significantly between the two groups. CONCLUSIONS: Our results suggest that peripheral neurodegenerative changes may occur even after mild or asymptomatic SARS-CoV-2 infection. No relevant microvascular changes were seen with OCT angiography and structural OCT parameters did not show any signs of optic neuropathy in post-COVID patients. In vivo confocal microscopy seems to be an important tool in monitoring peripheral neuropathy in patients after COVID-19.

Metabolomic Analysis of Serum and Tear Samples from Patients with Obesity and Type 2 Diabetes Mellitus.

Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were collected. The concentration of 23 amino acids and 10 biogenic amines in serum and tear samples was analyzed. Statistical analysis and Pearson correlation analysis along with network analysis were carried out. Compared to controls, changes in the level of 6 analytes in the obese group and of 10 analytes in the T2D group were statistically significant. For obesity, the energy generation, while for T2D, the involvement of NO synthesis and its relation to insulin signaling and inflammation, were characteristic. We found that BCAA and glutamine metabolism, urea cycle, and beta-oxidation make up crucial parts of the metabolic changes in T2D. According to our data, the retromer-mediated retrograde transport, the ethanolamine metabolism, and, consequently, the endocannabinoid signaling and phospholipid metabolism were characteristic of both conditions and can be relevant pathways to understanding and treating insulin resistance. By providing potential therapeutic targets and new starting points for mechanistic studies, our results emphasize the importance of complex data analysis procedures to better understand the pathomechanism of obesity and diabetes.

Comparative analysis of two optical biometry devices: high wavelength swept source OCT versus partial coherence interferometry.

PURPOSE: To study the reproducibility of measurements performed with a recently developed multimodal high resolution swept source optical coherence tomography (SSOCT) and to make comparisons with a partial coherence interferometry (PCI) biometer. METHODS: One hundred and fifty-two eyes of 152 subjects were involved in this study with a mean age of 65.71 ± 13.86 years (26-85 years). Anterior surface keratometry (K), anterior chamber depth (ACD), white-to-white (WTW) and axial length (AL) values were recorded by the SSOCT (ANTERION, Heidelberg Engineering Ltd, Germany) and PCI (IOLMaster 500, version 5.5, Carl Zeiss Meditec, Germany). Intraocular lens (IOL) power was calculated based on ANTERION and IOLMaster keratometry values by using five traditional vergence formulas. RESULTS: Anterior surface simulated keratometry values did not differ significantly between the IOLMaster and ANTERION (P > 0.05). AL measurements were successful in 95% of the cases both with the SSOCT and PCI. No significant difference was disclosed between the two instruments (P = 0.229). For WTW measurements, a significant difference was observed between the two optical biometers (P < 0.0001). The difference between PCI and SSOCT in IOL powers was statistically significant for SRK/T, Hoffer and Holladay formulas (P < 0.001). CONCLUSION: Our results implicated an overall good reproducibility of anterior keratometry, AL, ACD and WTW measurements for IOLMaster and ANTERION. The discrepancies between their measurements resulted in significant difference in the calculated IOL power for SRK/T, Hoffer and Holladay formulas, but not for Haigis formula.

Reliability and clinical applicability of a novel tear film imaging tool.

PURPOSE: The aim of our research was to investigate the reliability and clinical applicability of a modern tear film imaging tool by comparing the inter- and intragrader difference. The further goal was to compare the non-invasive tear break-up time (NIBUT) measured with the LacryDiag® device with traditional tear film break-up time (TBUT). METHODS: Comprehensive ophthalmological examination was performed, including LacryDiag® (Quantel Medical, France) (lower tear meniscus height measuring (LTMH), superior and inferior eyelid meibography (MeibS MeibI), interferometry (INT), NIBUT), slit lamp examination, and TBUT. Two independent, well-trained graders selected and analyzed the LTMH, MeibI, MeibS, and INT. The second grader reanalyzed the data 1 month later. Intra- and inter-examiner reliabilities were evaluated using intraclass correlation coefficients (ICC), while for categorical variable, Cohen's kappa statistics were provided. The Bland-Altman plot was used for visualization of the agreement between measurements. RESULTS: Fifty healthy volunteers were examined. For LTMH both the inter- and intragrader variabilities were excellent. Between two graders, the ICC of MeibI was poor; however, between two graders, the ICC of MeibS was good, and the intragrader variability in MeibI and MeibS was excellent. For the INT, both intra- and intergrading were in fair and moderate agreement, although the intragrader agreement was higher. Comparing the NIBUT and TBUT, the agreement was slight. CONCLUSION: Based on our results, examination of a patient during follow-up should be performed by the same examiner, because of the slight agreement. The LacryDiag® is a non-invasive, easy-to-use device, which can examine the tear film and save the recordings for easier follow-up.

In vivo corneal confocal microscopy and optical coherence tomography on eyes of participants with type 2 diabetes mellitus and obese participants without diabetes.

PURPOSES: To examine corneal nerve and retinal nerve characteristics of participants with type 2 diabetes mellitus (T2DM) compared with obese participants without diabetes to discover potential nerve vulnerabilities. METHODS: All participants underwent a complete medical examination including a physical examination and blood sample tests. The ophthalmologic examination included best-corrected visual acuity, intraocular pressure, Schirmer test, tear film breakup time, slit-lamp examination, dilated fundus photography, in vivo corneal confocal microscopy (IVCCM), and optical coherence tomography (OCT). RESULTS: The study cohort consisted of 83 eyes of 83 individuals: a group of 44 participants with T2DM, and a control group of 39 obese participants with no history of diabetes. Comparing measurements on the two groups, participants with T2DM had lower values with statistical significance for retinal nerve fiber layer (RNFL) nasal superior thickness (p = 0.010) and three corneal nerve (CN) parameters: fiber length (p = 0.025), total branch density (p = 0.013), and fiber area (p = 0.009). There was a borderline significant difference in CN fiber width (p = 0.051) and RNFL nasal inferior thickness (p = 0.056). No other significant differences were observed in the IVCCM and OCT parameters. No statistically significant correlation was found between CN and RNFL parameters. CONCLUSIONS: Progression from a pre-diabetic obese state to a T2DM condition might entail a loss or diminishment of certain corneal nerve fibers or retinal nerve fibers, but not necessarily a loss of both corneal and retinal nerve fibers simultaneously. Using IVCCM and OCT together enables monitoring of both corneal and retinal health of the eye.

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats.

Glaucoma is associated with increased intraocular pressure (IOP), causing the apoptosis of retinal ganglion cells (RGCs) and the loss of their axons leading to blindness. Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in several neural injuries, including retinopathies. The aim of this study was to investigate the effects of PACAP1-38 eye drops in a model of glaucoma. IOP was elevated bilaterally by injections of microbeads to block the aqueous humor outflow. The control groups received the same volume of saline. Animals were treated with PACAP1-38 (1 µg/drop, 3 × 1 drop/day) or vehicle for 4 weeks starting one day after the injections. Retinal morphology by histology and optical coherence tomography, function by electroretinography, and IOP changes were analyzed. Animals were sacrificed 8 weeks after the injections. Microbeads injections induced a significant increase in the IOP, while PACAP1-38 treatment lowered it to normal levels (~10 mmHg). Significant retinal degeneration and functional impairment were observed in the microbead-injected group without PACAP1-38 treatment. In the microbeads + PACAP1-38 group, the retinal morphology and functionality were close to the normal values. In summary, our results show that PACAP1-38, given in form of eye drops, is neuroprotective in glaucoma, providing the basis for potential future therapeutic administration.

Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study.

PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test. RESULTS: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU. CONCLUSIONS: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.

Wound-Healing Markers Revealed by Proximity Extension Assay in Tears of Patients following Glaucoma Surgery.

Tears are a constantly available and highly valuable body fluid collectable by non-invasive techniques. Although it can give information on ocular status and be used for follow-ups, tear analysis is challenging due to the low amount of sample that is available. Proximity extension assay (PEA) allows for a sensitive and scalable analysis of multiple proteins in a single run from a one-µL sample, so we applied this technique and examined the amount of 184 proteins in tears collected at different time points after trabeculectomy. The success rate of this surgical intervention highly depends on proper wound healing; therefore, information on the process is indispensable. We observed significantly higher levels of IL-6 and MMP1 at the early time points (day one, two, and four) following trabeculectomy, and the protein amounts went back to the level observed before the surgery three months after the intervention. Patients with or without complications were tested, and proteins that have roles in the immune response and wound healing could be observed with altered frequency and amounts in the cases of patients with complications. Our results highlight the importance of inflammation in wound-healing complications, and at the same time, indicate the utility of PEA in tear analysis.

[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.

A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration-Like Lesions at the Peripheral Retina.

PURPOSE: Our understanding of the relevance of peripheral retinal abnormalities to disease in general and in age-related macular degeneration (AMD) in particular is limited by the lack of detailed peripheral imaging studies. The purpose of this study was to develop image grading protocols suited to ultra-widefield imaging (UWFI) in an aged population. DESIGN: A cross-sectional study of a random population sample in which UWFI was introduced at the 12-year review of the Reykjavik Eye Study in Iceland. PARTICIPANTS: Five hundred seventy-six subjects 62 years of age or older. METHODS: Ultra-widefield (up to 200°) color and autofluorescence images were obtained using the Optos P200CAF laser scanning ophthalmoscope (Optos plc, Dunfermline, Scotland). The images were graded at Moorfields Eye Hospital Reading Centre primarily based on the International Classification for AMD. Macular and peripheral changes were graded using a standardized grid developed for this imaging method. MAIN OUTCOME MEASURES: Presence or absence of hard, crystalline, and soft drusen; retinal pigment epithelial changes; choroidal neovascularization (CNV); atrophy; and hypoautofluorescence and hyperautofluorescence were graded in the peripheral retina. RESULTS: Of the eyes examined, 81.1% had AMD-like changes in the macula alone (13.6%), periphery alone (10.1%), and both periphery and macula (57.4%). There was no AMD-like CNV or pigment epithelial detachment in the periphery except in those cases in which these clearly originated from the macula. Seven patients had AMD-like atrophy in the periphery without end-stage disease in the macula. One patient with end-stage disease in the macula had normal periphery results on the color images. While analyzing the eyes, we detected pathologic appearances that were very reliably identified by graders. CONCLUSIONS: Phenotyping the retinal periphery using the categories defined by the International Classification confirmed the presence of wide-ranging AMD-like pathologic changes even in those without central sight-threatening macular disease. Based on our observations, we propose here new, reliably identifiable grading categories that may be more suited for population-based UWFI.

Relative quantification of human ß-defensins by a proteomics approach based on selected reaction monitoring.

RATIONALE: A targeted proteomics method based on selected reaction monitoring (SRM) is a relevant approach for the analysis of multiple analytes in biological samples. Defensins are phylogenetically conserved small antimicrobial peptides contributing to innate host defense and exhibiting low immunogenicity, resistance to proteolysis and a broad range of antimicrobial activities. The goal of the present study was to develop and optimize SRM-based targeted proteomics methods for the detection of human ß-defensins 1-4 in various biological fluids. METHODS: An SRM-based targeted proteomics method was developed and validated for the detection of human ß-defensins 1-4. The supernatants of resting and IL-1ß-stimulated Caco2, HT-29 and SW-1116 colonic epithelial cells (CEC), cell lysates of CECs and tear samples of human healthy individuals were analyzed and the feasibility of the developed method was validated by ELISA and dot-blot analysis complemented by RT-qPCR. RESULTS: Our results demonstrate that the developed SRM method offers an alternative approach for the cost-effective and rapid analysis of human ß-defensins in samples with biological relevance. CONCLUSIONS: A semi-quantitative targeted mass spectrometry method was developed and validated for the relative quantification of ß-defensins 1-4 in cell culture supernatants and body fluid analyses.

Astigmatism and maternal myopia as important factors affecting success rate of DIMS lens treatment.

OBJECTIVE: To assess the efficacy of myopia control spectacle lenses (defocus incorporated multiple segments/DIMS) in slowing myopia progression among a diverse Central European paediatric population and investigate the contribution of baseline parameters on treatment outcomes. METHODS AND ANALYSIS: This retrospective observational study included 62 individuals aged 4-17 years (mean±SD: 10.21±2.70) with progressing myopia but without ocular pathology with a range of -0.88 to -8.25 D spherical equivalent refraction (SER) (-3.73±1.56), coupled with astigmatism up to -3.25 D cylindrical. All participants were prescribed DIMS (Hoya MiyoSmart) spectacles. Key outcome variables were cycloplegic SER, measured for all participants and axial length (AL), assessed in a subset of patients, recorded at baseline, 6 months and 12 months. Quality of life assessments were conducted at baseline, at 2 weeks, and 3, 6, 9 and 12 months. Additionally, parental myopic dioptre was recorded when applicable. RESULTS: At the 12-month mark, myopia progression in patients (mean±SE: -0.40±0.05) mirrored findings from prior European DIMS studies, but with 50% of patients showing no progression. A multivariate analysis of covariance model revealed that baseline astigmatism and younger age adversely affected therapy outcomes in both SER and AL, while severe maternal myopia led to greater SER progression. In contrast, only young age but not astigmatism was associated with AL increase in a comparable group of children with myopia, part of the LIFE Child Study, wearing single-vision spectacles. Patients reported consistent satisfaction with treatment, with minimal side effects, which diminished over the year. CONCLUSION: In the European population, astigmatism, young age and severe maternal myopia are risk factors for suboptimal outcomes following DIMS therapy. Further research is necessary to elucidate the impact of astigmatism on myopic defocus therapy.

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.

Ocular Manifestations of Hurler-Scheie Syndrome: Recurrence of Host Disease in the Corneal Transplant.

Introduction: Hurler-Scheie syndrome is a type of mucopolysaccharidosis I (MPS). In MPS I the decreased activity of alpha-L-iduronidase lysosomal enzyme leads to glycosaminoglycan (GAG) deposition in the intra- and extracellular matrix. Excessive amounts of GAG can accumulate in most layers of the cornea, including epithelial cells, stromal keratocytes, and endothelial cells. Case Presentation: A 25-year-old female patient suffering from Hurler-Scheie syndrome with multiple ocular manifestations is reported. Due to significant bilateral corneal opacification, penetrating keratoplasty was performed on both eyes. Histopathologic examination of the corneal buttons showed disorganized collagen fibers with heterogenous thickness and many granule-containing keratocytes with excessive cytoplasm. Despite receiving enzyme replacement therapy, in vivo confocal microscopy revealed characteristic vacuoles in the basal epithelium and corneal stroma 96 months after transplantation. High resolution anterior segment optical coherence tomography demonstrated hyperreflective opacities superficial and deeper in the stroma which was consistent with recurrence of host disease in the graft. Conclusion: To the best of our knowledge, this is the first documented Hurler-Scheie syndrome case of recurrence after penetrating keratoplasty demonstrated by in vivo confocal microscopy. Additionally, this patient manifested severe ocular involvement of MPS which might be an explanation of the progressive course of corneal opacification after transplantation.