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    Conjunctival impression cytology and tear film parameters in patients with multiple sclerosis
    (Springer, 2022) Belviranli, Selman; Oltulu, Pembe; Uca, Ali Ulvi; Gundogan, Ali Osman; Mirza, Enver; Altas, Mustafa; Turk, Nazli
    Purpose To evaluate conjunctival impression cytology (CIC) findings and tear film parameters in patients with multiple sclerosis (MS) compared with controls. Methods Thirty-three patients with MS (MS group) and 33 age- and sex-matched healthy subjects (control group) were included in this cross-sectional comparative study. CIC grades, tear break-up time (TBUT), Schirmer 1 test results, and Ocular Surface Disease Index (OSDI) scores were compared between the two groups, and correlations between CIC grade, TBUT, Schirmer 1 test result, OSDI score, Expanded Disability Status Scale score, and disease duration were analyzed. Results Mean CIC grade was higher in the MS group than in the control group (1.48 +/- 0.71 and 0.39 +/- 0.56, respectively; p < 0.001). In the MS group, CIC of the 14 participants (42.4%) was grade 2-3. In the control group, CIC of the only one participant (3.3%) was grade 2, and none of them was grade 3. TBUT (8.12 +/- 3.16, 13.06 +/- 4.23 s in MS and control groups, respectively; p < 0.001) and Schirmer 1 test results (8.45 +/- 5.75, 17.36 +/- 10.89 mm in MS and control groups, respectively; p < 0.001) were lower, and OSDI score (36.36 +/- 19.19, 13.70 +/- 15.36 in MS and control groups, respectively; p < 0.001) was higher in the MS group compared to the control group. Conclusion In patients with MS, objective findings of dry eye, subjective symptoms related to dry eye, and CIC abnormalities, including high grades of conjunctival squamous metaplasia and goblet cell loss, are more common. Patients with MS should be monitored for ocular surface alterations and dry eye disease.
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    Evaluation of inflammatory biomarkers in patients with keratoconus
    (Sage Publications Ltd, 2022) Oltulu, Refik; Katipoglu, Zeynep; Gundogan, Ali Osman; Mirza, Enver; Belviranli, Selman
    Objective: To investigate the monocyte-to-HDL-cholesterol ratio (MHR), neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), eosinophil-to-lymphocytes ratio (ELR), platelet distribution width (PDW), red blood cell distribution width (RDW), mean platelet volume (MPV), MPV to platelet count ratio (MPV/PC), and RDW to platelet ratio (RPR) that are accepted as inflammatory markers in patients with keratoconus. Methods: In this study, 43 patients with keratoconus and 43 healthy individuals as the control group were retrospectively evaluated. High density lipoprotein cholesterol (HDL-c), lymphocyte, neutrophil, eosinophil, monocyte, platelet, MPV, PDW, and RDW values were obtained with complete blood count performed on the peripheral blood samples. Results: Absolute monocyte (593 +/- 182 vs 492 +/- 177; p < 0.05) and neutrophil (4860 +/- 1553 vs 3954 +/- 1297; p < 0.01) counts were statistically significantly higher in the keratoconus groups compared to the control group. MHR (13.18 +/- 5.02 vs 9.88 +/- 4.45; p < 0.01) and NLR (2.30 +/- 0.87 vs 1.77 +/- 0.61; p < 0.01) were statistically significantly higher and LMR (4.07 +/- 1.67 vs 5.18 +/- 2.06; p < 0.01) was significantly lower in the keratoconus group. As a result of univariate logistic regression analysis, it was observed that MHR and NLR were statistically significant relationship with keratoconus (p = 0.02 and p = 0.021) (Odds ratio = 5.41 (95% CI: 1.169-6.669) and Odds ratio:5.28 (95% CI: 1.024-6.321); respectively). No statistically significant difference was found between the groups in terms of PLR, ELR, RDW, MPV, PDW, MPV/PC, and RPR. Adjusting for age and gender, multivariate regression analysis revealed that MHR was the most significant parameter to demonstrate relationship with keratoconus (p = 0.025) (Odds ratio = 4.99 (95% CI: 1.019-6.332)). Conclusion: MHR and NLR values considered as inflammatory markers were statistically significantly higher and LMR value was significantly lower in the keratoconus group. Among these values, MHR was the most reliable parameter.
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    Expression of placental growth factor, neuropilin-1, and neuropilin-2 in primary pterygium tissue
    (Springer, 2023) Gundogan, Ali Osman; Oltulu, Refik; Belviranli, Selman; Oltulu, Pembe
    Purpose The aim of this study was to evaluate the expression of placental growth factor (PLGF), neuropilin-1 (NP-1), and neuropilin-2 (NP-2) molecules in primary pterygium tissue compared with normal conjunctival tissue.Methods The records of 42 patients who underwent excision surgery with autografts for primary pterygium (pterygium group) and 20 patients who underwent conjunctival nevus excision surgery (control group) in the same period were reviewed retrospectively. The samples obtained from the pterygium tissues in the pterygium group and the clean conjunctival tissues adjacent to the nevus in the control group were collected from the archive. Immunohistochemical stains of the primary antibodies-1/100 diluted PLGF, NP-1, and NP-2 (Abcam Cambridge Science Park, UK)-were applied to all groups. Staining intensities and the percentage of positive cells in epithelial, endothelial, stromal, and inflammatory cells were analyzed by an experienced pathologist.Results The positivity rates of PLGF and NP-2 expression in epithelial, endothelial, stromal, and inflammatory cells were found to be higher in the pterygium group than in the control group (PLGF: p < 0.001, p < 0.001, p = 0.001, and p < 0.001, respectively; NP-2: p < 0.001 for all). Staining intensities for PLGF and NP-2 were higher in the pterygium group than in the control group (PLGF: p < 0.001, p < 0.001, p = 0.005, and p < 0.001, respectively; NP-2: p < 0.001, p < 0.001, p = 0.001, and p < 0.001, respectively). However, no significant differences were found in any cell type in terms of NP-1 expression positivity rates (p = 0.730, p = 0.121, p = 0.524, and p = 0.624, respectively) or staining intensity (p = 0.716, p = 0.147, p = 0.147, and p = 0.780, respectively).Conclusion PLGF and NP-2 levels were found to be higher in pterygium tissue, while there was no difference in NP-1. These results indicate the possible roles of NP-2 and PLGF in primary pterygium.
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    Impact of unilateral trigeminal neuralgia on bilateral ocular surface alterations
    (Wiley, 2022) Altas, Mustafa; Oltulu, Pembe; Uca, Ali Ulvi; Belviranli, Selman; Gundogan, Ali Osman; Mirza, Enver; Oltulu, Refik
    Objective To evaluate ocular surface alterations in both eyes of patients with unilateral trigeminal neuralgia (TN) compared with controls. Background Corneal nerves mainly originate from the trigeminal nerve, and neurosensory abnormalities are important factors in ocular surface alterations and dry eye etiopathogenesis. Methods Twenty-four patients with idiopathic unilateral TN and 24 healthy controls with similar sex and age distributions were included in this cross-sectional study conducted from February 15 to September 15, 2021. The eyes on the affected sides of the patients with TN were treated as Group 1, their contralateral eyes as Group 2, and the right eyes of the controls as Group 3. All participants were evaluated for tear film and ocular surface using the Schirmer 1 test, tear breakup time (TBUT), Ocular Surface Disease Index (OSDI) score, and conjunctival impression cytology grading. Results The mean (SD) ages of the patients with TN (17 of 24 females, 70.8%) and controls (15 of 24 females, 62.5%) were 49.7 (11.7) and 48.5 (9. 6) years, respectively. The median [25th, 75th percentile] Schirmer 1 test results in Groups 1, 2, and 3 were 5.0 [4.0, 14.0], 7.0 [3.2, 11.7], and 10.0 [6.0, 15.7] mm, respectively, with no statistically significant differences between Groups 1 and 2 (p = 0.697), Groups 1 and 3 (p = 0.133), or Groups 2 and 3 (p = 0.129). The median TBUT scores in Groups 1, 2, and 3 were 7.0 [5.0, 10.0], 8.0 [5.2, 10.0], and 12.5 [8.0, 13.0] s, respectively, showing reduced times for both Groups 1 and 2 versus Group 3 (median difference = -3.0 [95% CI: -5.0, -1.0], p = 0.001, and median difference = -3.0 [95% CI: -5.0, -2.0], p = 0.001, respectively). Conjunctival impression cytology grades were significantly higher in Groups 1 and 2 versus Group 3 (median difference = 2.0 [95% CI: 1.0, 2.0], p < 0.001, and median difference = 1.0 [95% CI: 1.0, 2.0], p < 0.001, respectively). The median OSDI score in TN patients (30.2 [25.0, 34.9]) was significantly higher than in the controls (8.3 [0.0, 18.7]), with a median difference of 20.8 (95% CI: 14.7, 27.1), p < 0.001. Conclusion Even if pain is unilateral in patients with TN, there are significant abnormalities in conjunctival cytology and tear functions in both eyes. There seem to be various pathophysiological mechanisms of TN that affect the bilateral ocular surface and lead to significant alterations.
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    Quantitative assessment of the effect of SARS-CoV-2 on the corneal sub-basal nerve plexus of post-COVID-19 patients using in vivo confocal microscopy
    (Springernature, 2023) Mirza, Enver; Belviranli, Selman; Gundogan, Ali Osman; Adam, Mehmet; Oltulu, Refik
    Objectives To investigate whether SARS-CoV-2 causes morphological changes in the corneal sub-basal nerve plexus (CSNP) of post-COVID-19 patients using in vivo confocal microscopy (IVCM). Methods A total of 70 participants were included in the study and were divided into three groups. Post-COVID-19 patients with neurological manifestations were considered Group 1 (n = 24), and post-COVID-19 patients without neurological manifestations were considered Group 2 (n = 24). Healthy control participants were considered Group 3 (n = 22). The parameters of the CSNP, including nerve fibre density (NFD), nerve branch density (NBD), and nerve fibre length (NFL), were investigated in all participants using IVCM. Additionally, corneal sensitivity was tested by corneal esthesiometry. Results The mean NFD, NBD, and NFL values of Group 1 (16.12 +/- 4.84 fibre/mm(2), 27.97 +/- 9.62 branch/mm(2), and 11.60 +/- 2.89 mm/mm(2)) were significantly lower than those of Group 2 (19.55 +/- 3.01 fibre/mm(2), 40.44 +/- 7.16 branch/mm(2), and 15.92 +/- 2.08 mm/mm(2)) and Group 3 (25.24 +/- 3.75 fibre/mm(2), 44.61 +/- 11.80 branch/mm(2), and 17.76 +/- 3.32 mm/mm(2)) (p < 0.05 for all). Except the mean NFD value (p < 0.001), there were no significant differences in terms of the mean NBD and NFL values between Group 2 and Group 3 (p = 0.445, p = 0.085). The value of the mean corneal sensitivity was significantly higher in Group 3 (59.09 +/- 1.97 mm) compared to Group 1 (55.21 +/- 1.02 mm) and Group 2 (55.28 +/- 1.18 mm) (p < 0.001, p < 0.001) but there was no significant difference between Group 1 and Group 2 (p = 1.000). Conclusion In post-COVID-19 patients, the mean parameters of CSNP were lower than in the control group. These differences were more pronounced in patients who had neurological manifestations of COVID-19.