The Severity of Diabetic Retinopathy Corresponds with Corneal Nerve Alterations and Ocular Discomfort of the Patient.

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35-+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = -0.26, 95% CI: -0.44--0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-ß, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM.

Successive Acanthamoeba Corneal Isolates Identified in Poland Monitored in Terms of In Vitro Dynamics.

BACKGROUND: Amoebae of the genus Acanthamoeba cause a sight-threatening infection called Acanthamoeba keratitis. It is considered a rare disease in humans but poses an increasing threat to public health worldwide, including in Poland. We present successive isolates from serious keratitis preliminary examined in terms of the identification and monitoring of, among others, the in vitro dynamics of the detected strains. METHODS: Clinical and combined laboratory methods were applied; causative agents of the keratitis were identified at the cellular and molecular levels; isolates were cultivated in an axenic liquid medium and regularly monitored. RESULTS: In a phase-contrast microscope, Acanthamoeba sp. cysts and live trophozoites from corneal samples and in vitro cultures were assessed on the cellular level. Some isolates that were tested at the molecular level were found to correspond to A. mauritanensis, A. culbertsoni, A. castellanii, genotype T4. There was variability in the amoebic strain dynamics; high viability was expressed as trofozoites' long duration ability to intense multiply. CONCLUSIONS: Some strains from keratitis under diagnosis verification and dynamics assessment showed enough adaptive capability to grow in an axenic medium, allowing them to exhibit significant thermal tolerance. In vitro monitoring that was suitable for verifying in vivo examinations, in particular, was useful to detect the strong viability and pathogenic potential of successive Acanthamoeba strains with a long duration of high dynamics.

IgA-Based Secretory Response in Tears of COVID-19 Patients: A Potential Biomarker of Pro-Inflammatory State in Course of SARS-CoV-2 Infection.

Mucosal immunity, including secretory IgA (sIgA), plays an important role in the early defence against SARS-CoV-2 infection. However, a comprehensive evaluation of the local immune response in tears in relation to blood antibody reservoirs has not yet been conducted. A total of 179 symptomatic laboratory-confirmed COVID-19 patients were included in this single-centre study. Conjunctival swabs were analysed by a reverse transcription polymerase chain reaction for the detection of SARS-CoV-2 RNA. In parallel, tear samples collected by Schirmer test strips and plasma samples were analysed by ELISA to detect anti-S1 IgA levels. The concentrations of selected inflammatory cytokines in tears were determined by a magnetic bead assay. Anti-SARS-CoV-2 sIgA was present in the tears of 81 (45.25%) confirmed COVID-19 patients, and the tear IgA levels were correlated with the plasma IgA levels (Rs = +0.29, p = 0.0003). SARS-CoV-2 RNA in the conjunctival sac was identified in 18 COVID-19 patients (10%). Positive correlations between the tear IgA level and the concentrations of several cytokines TNF-α (Rs = +0.23, p = 0.002), IL-1ß (Rs = +0.25, p < 0.001), IL-2 (Rs = +0.20, p = 0.007), IL-4 (Rs = +0.16, p = 0.04), IL-5 (Rs = +0.36, p < 0.001), IL-6 (Rs = +0.32, p < 0.001), IL-8 (Rs = +0.31, p < 0.001), VEGF (Rs = +0.25, p < 0.001) and GM-CSF (Rs = +0.27, p < 0.001) were also found. Quantitative tear film-based sIgA could potentially serve as a rapid and easily accessible biomarker of external mucosal immunity to SARS-CoV-2. The concentration of sIgA is directly related to individual host immune responses to SARS-CoV-2 infection.

Evaluating Ocular Symptoms and Tear Film Cytokine Profiles in Symptomatic COVID-19 Patients.

Background: This study investigated the presence and duration of ophthalmic symptoms in the early phase of COVID-19 to assess the corresponding local immune response on the ocular surface. Methods: The study included data from 180 COVID-19 patients and 160 age-matched healthy controls. The main finding was the occurrence of ophthalmological manifestations at the time of admission to the hospital and during the preceding 7 days. Tear film concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay. Results: Among the COVID-19 patients, 12.64% had at least one ocular symptom at the time of admission, and 24.14% had symptoms within the preceding 7 days (p < 0.001 vs. controls). We found that the COVID-19 patients complained more frequently about eye tearing (p = 0.04) and eye pain (p = 0.01) than controls. A multivariate analysis of the patients and controls adjusted for age and sex revealed that COVID-19 was an independent factor associated with higher VEGF and IL-10 tear film concentrations (ß = +0.13, p = 0.047 and ß = +0.34, p < 0.001, respectively) and lower IL-1ß, IL-8, and GM-CSF levels (ß = −0.25, p < 0.001; ß = −0.18, p = 0.004; and ß = −0.82, p = 0.0 respectively). Conclusions: SARS-CoV-2 does not attract a strong local response of the conjunctival immune system; therefore, ophthalmic symptoms may not constitute a substantial element in the clinical picture of novel COVID-19 infection.

Increased proinflammatory cytokines in tears correspond with conjunctival SARS-CoV-2 positivity in symptomatic COVID-19 patients.

Tear fluid cytokine levels may serve as biomarkers of innate immune system response against SARS-CoV-2 infection. Therefore, our aim was to analyze panel of selected inflammatory cytokines in tears of COVID-19 patients in relation to presence of SARS-CoV-2 viral load in conjunctival secretions. In this study concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay in tear film collected from 232 symptomatic COVID-19 patients. SARS-CoV-2 ocular infection was confirmed based on positive conjunctival swab-based RT-PCR testing. Viral RNA in conjunctival sac was detected in 21 patients (9%). No relation between presence and the duration of ophthalmic symptoms and SARS-CoV-2 infection detected in conjunctival secretions was found. The tear film concentrations of IFN-γ, TNF-α, IL-5, IL-8 and GM-CSF were found to be significantly greater among patients with positive conjunctival swab results as compared to the group negative for SARS-CoV-2 in conjunctival sac. Our current data depict a group of inflammatory mediators in human tears, which may play a significant role in ocular pathology of SARS-CoV-2 conjunctival infection.

Comparative Analysis of Corneal Parameters in Swept-Source Imaging between DMEK and UT-DSAEK Eyes.

BACKGROUND: The need to provide a comparative analysis of corneal parameter changes compared to their preoperative values between Descemet membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) patients. METHODS: The study included 24 eyes after UT-DSAEK and 24 eyes after DMEK. Visual acuity, endothelial cell count (ECC), central corneal thickness (CCT), mean keratometry (MK), mean astigmatism (MA), astigmatism asymmetry (AA) and higher-order aberrations (HOAs) were assessed at baseline and 1, 3, 6 and 12 months after the surgery. RESULTS: From the 3rd month post operation, ECC was higher in the DMEK eyes than in the UT-DSAEK eyes (p = 0.01). In a bivariate analysis that was adjusted for age, DMEK was associated with a smaller decrease in posterior MK at the 1-month (ß = -0.49, p = 0.002), 3-month (ß = -0.50, p < 0.001), 6-month (ß = -0.58, p < 0.001) and 12-month (ß = -0.49, p < 0.001) follow-up visits. There were no significant differences in changes in anterior or combined surface MK throughout the observation period. Accordingly, no significant differences in changes in MA, AA or HOAs compared to the baseline values were identified between the eyes after DMEK and UT-DSAEK at any follow-up time point. CONCLUSIONS: UT-DSAEK seemed to be an easier and safer technique than DMEK while maintaining similar outcomes regarding irregular astigmatism and total keratometry values.

Changes in Corneal Parameters after DMEK Surgery: A Swept-Source Imaging Analysis at 12-Month Follow-Up Time.

PURPOSE: To assess the time course changes in corneal topographic parameters during the one-year follow-up after Descemet membrane endothelial keratoplasty (DMEK) surgery. MATERIALS AND METHODS: Twenty-one patients (24 eyes) who underwent DMEK surgery were evaluated. Best corrected visual acuity (BCVA), endothelial cell count (ECC), central corneal thickness (CCT), mean keratometry (MK), mean astigmatism (MA), astigmatism asymmetry (AA), and higher-order aberration (HOA) were assessed at baseline and 1, 3, 6 and 12 months after the surgery using CASIA2 anterior segment swept-source OCT (Tomey, Japan). RESULTS: In patients who underwent DMEK surgery, BCVA improved gradually at the subsequent visits during the 12-month follow-up. A significant reduction in ECC and CCT at the 1st month was noted, which remained stable until the 6th month postoperatively. Anterior and total MK values remained unchanged, whereas changes in posterior keratometry were noticeable until the 6th month after surgery. A significant reduction in the anterior, posterior, and total astigmatism magnitude as well as astigmatism asymmetry was observed during the first 6 months after surgery. A gradual anterior, posterior, and total HOA decrease was documented until the 12th month after surgery. Negative correlations between baseline values of CCT, MK, MA, AA, and HOA and postoperative variations in those parameters at consecutive follow-up time points were observed. Accordingly, negative correlations between baseline CCT and postoperative changes in corneal topographic parameters after surgery were found. CONCLUSION: The stabilization of most corneal topographic parameters takes place within 6 months after the procedure, whereas HOA reduction and BCVA improvement gradually occur during the first year after surgery. Preoperative values of corneal topographic parameters strongly determine their changes detected after DMEK surgery, which may suggest that early therapeutic intervention results in better visual outcomes.

The circulating vascular endothelial growth factor is only marginally associated with an increased risk for atherosclerosis.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) is a protein that plays a role in the formation and function of blood vessels, promotes increased vascular permeability or migration of monocytes through endothelial layers. We have tested the hypothesis that plasma levels of VEGF-A may be associated with biochemical and radiological parameters as a marker of cardiovascular risk in Caucasian patients with early-onset CAD. METHODS: The study group included 100 patients: 75 men not older than 50 years and 25 women not older than 55 years at the moment of CAD diagnosis. The control group (patients without CAD) comprised 50 healthy cases. ELISA test was used to measure plasma concentrations of VEGF. Doppler ultrasound of carotid and peripheral arteries was carried out in each patient. Serum glucose, complete lipid profile, ApoA1, ApoB, Lp(a) and blood count were measured in each case. RESULTS: Only very weak correlations of plasma VEGF levels with biochemical cardiovascular risk factors in the CAD subjects have been demonstrated. In the study group, VEGF concentration was significantly positively correlated with the same blood parameters as white blood cells, platelets, plateletcrit, apolipoprotein B, total and LDL cholesterol fraction. The plaque of common carotid arteries and bifurcation was present in 39% of CAD patients, however, there was no significant association between VEGF plasma concentration and any measured parameters in Doppler ultrasound of carotid and peripheral arteries. CONCLUSIONS: The circulating VEGF is only marginally associated with an increased risk for atherosclerosis.

Associations between IL-6 and Echo-Parameters in Patients with Early Onset Coronary Artery Disease.

BACKGROUND: Over the last two decades, many studies have investigated the association between interleukin 6 (IL-6) and pathogenesis and progression of coronary artery disease (CAD). Patients with CAD manifested at a young age are a particularly interesting group. They differ from older patients, not only in terms of the severity of coronary artery atherosclerosis, but also risk factor profiles, short- and long-term prognosis after myocardial infarction (MI). The role of IL-6 in younger patients with CAD is less well-known. Therefore, our study aimed to analyze the relationship between IL-6 level and other inflammations, atherosclerosis, and cardiac function parameters in early onset CAD patients. METHODS: The study covered 100 patients with early onset CAD and a group of 50 healthy participants. Plasma levels of IL-6 and basic biochemical parameters, anthropometric, echocardiographic, and arteries Doppler ultrasound measurements were performed. RESULTS: We did not observe a significant difference in IL-6 concentration in plasma between patients with early onset CAD and a control group, but IL-6 level was negatively correlated with echocardiographic measurements of ascending aorta diameter, left ventricular shortening fraction, and right ventricular end-diastolic diameter in our patients. CONCLUSIONS: In patients with early onset CAD, plasma IL-6 level is associated with other inflammation parameters and with cardiac function, potentially contributing to right ventricular remodeling and left ventricular systolic dysfunction. This suggests possible prognostic benefits of long-time observation of IL-6 level after the acute coronary syndrome.