Crosstalk among miR-29, α-SMA, and TGFß1/ß3 in melatonin-induced exosome (Mel-prExo) treated human limbal mesenchymal stem cells (hLMSCs): An insight into scarless healing of the cornea.

Inflammatory mediators that infiltrate the corneal stroma after corneal infections, trauma or refractive surgery can trigger the transformation of corneal keratocytes into myofibroblasts, resulting in highly irregular collagen deposition and subsequently corneal scarring. Mesenchymal stem cells (MSCs) can be used as therapeutic agents to regenerate corneal and conjunctival tissue damage, regulate inflammation, and reduce the development of limbal stem cell failure. The use of MSC-derived exosomes as a cell-free therapeutic vector is a novel therapeutic approach. This study aimed to assess the effect of exosomes obtained from melatonin (Mel)-treated human limbal mesenchymal stem cells (hLMSCs) on naïve hLMSCs and to determine their influence on the antifibrotic and pro-regenerative pathways involved in corneal scarring. hLMSCs were treated with varying concentrations of Mel, followed by isolation and characterization of the procured exosomes (Mel-prExos). These exosomes were added to the cell culture media of naïve hLMSCs to examine their antifibrotic and pro-regenerative effects. The expression of miR-155, miR-29, TGFß1, TGFß3, PPARγ, and α-SMA miRNAs and genes were compared between Mel-treated hLMSCs and Mel-prExo-treated hLMSCs by using real-time PCR. We found that at 1 µM Mel and in the presence of Mel-prExos, TGFß1 was expressed 0.001-fold, while TGFß3 was expressed 0.6-fold. miR-29 expression was increased 38-fold in the control-Exo group compared to that in the control group. Changes in TGFß1/ß3 and α-SMA expression are associated with miR-29 and miR-155. This approach could prove beneficial for ocular surface tissue engineering applications.

Comparison of blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus and healthy subjects.

PURPOSE: To evaluate blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus (KC) and healthy subjects. SETTING: Eskisehir Osmangazi University, Eskisehir, Turkey. DESIGN: Cross-sectional study. METHODS: 100 KC patients (patient group) between the ages of 18 to 35 years and 200 healthy individuals (control group) in the same age range were included in the Eskisehir Osmangazi University Hospital Eye Clinic between October 2019 and March 2020. In all cases, a complete ophthalmologic examination and corneal tomography evaluation with a Pentacam Scheimpflug camera were performed. In blood samples, vitamin B12 and folic acid levels were measured using an electrochemiluminescence immunoassay analyzer, and homocysteine and riboflavin levels were measured using high-performance liquid chromatography. Chi-square tests were used in the analysis of categorical variables, and Mann-Whitney U and Kruskal-Wallis tests were used in the analysis of numerical variables. RESULTS: Homocysteine (13.0 ± 6.6 vs 12.1 ± 5.4 µmol/L, P = .190), vitamin B12 (313.5 ± 119.4 vs 322.9 ± 128.3 pg/mL, P = .619), and folic acid (7.0 ± 2.7 vs 7.4 ± 2.9 ng/mL, P = .230) levels were not different between KC (100 eyes of 100 subjects) and control (200 eyes of 200 subjects) groups. The mean riboflavin level was 84.0 ± 21.8 µg/L in the patient group and 183.6 ± 74.3 µg/L in the control group, with a significant difference between the 2 groups ( P < .001). Riboflavin levels were below 180 µg/L in 99% (n = 99) of the cases in the KC group and 53.5% (n = 107) in the control group ( P < .001). CONCLUSIONS: Low blood riboflavin levels in KC patients may be a possible risk factor in the pathogenesis of KC.

Risk factors for hypertensive phase after Ahmed glaucoma valve implantation.

PURPOSE: To investigate the risk factors and the clinical characteristics of the hypertensive phase (HP) after Ahmed glaucoma valve (AGV) implantation. METHODS: This retrospective study included 60 eyes of 57 patients who underwent AGV implantation and with at least 1-year follow-up. HP was defined as intraocular pressure (IOP) > 21 mmHg in the first 3 months after the surgery. Independent samples t-test and Chi-square test were used to compare differences in patients with the HP and the non-HP groups. Univariable and multivariable logistic regression analyses were used to determine the risk factors for the development of the HP. Statistical significance was assumed at p < 0.05 level. RESULTS: HP was observed in 31 eyes (51.7%) with an average peak IOP of 27.6 ± 4.5 mmHg (range 22-40 mmHg). The resolution of HP was noted in 27 eyes (87.1%) at the 3rd month postoperative visit. The number of glaucoma medications at the last postoperative visit and IOP values from 1 month to 1 year were significantly higher in the HP group (all p < 0.05). Patients with traumatic glaucoma showed the highest rate (83.3%) of HP development. In the multivariable analysis, a preoperative IOP > 30 mmHg (p = 0.03, OR:5.82; reference: ≤ 25 mmHg) and younger age (41-64 years, p = 0.02, OR:8.49; ≤ 40 years, p = 0.001, OR:19.62; reference: ≥ 65 years) were independently associated with the occurrence of HP. CONCLUSION: Hypertensive phase was observed in half of the patients undergoing AGV implantation. A higher mean preoperative IOP and younger age were risk factors for HP development. Although the majority resolved at the 3-month visit, eyes with HP had higher mean IOPs and required more IOP lowering medications.

The relationship of retinopathy of prematurity with brain-derivated neurotrophic factor, vascular endotelial growth factor-A, endothelial PAD domain protein 1 and nitric oxide synthase 3 gene polymorphisms.

BACKGROUND: In addition to risk factors such as low birth weight and uncontrolled oxygen therapy, genetic predisposition is also thought to play a role in the development of retinopathy of prematurity (ROP). In our study, we aimed to analyze single-nucleotide polymorphisms (SNPs) in VEGFA, EPAS1, BDNF and NOS3 genes in infants who develop ROP. MATERIALS AND METHODS: Seventy-five mild-moderate and 73 severe ROP cases were included in this study. Eleven different SNPs regions that located in VEGFA, EPAS1, BDNF and NOS3 genes were analysed by SnapShot technique and compared between two groups by the multiple logistic regression analysis. RESULTS: Statistically significant results were obtained in 8 of the 11 SNPs. It was observed that the excess of mutant alleles in four (VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744) of these regions increased ROP severity and treatment requirement (p < .001, p < .001, p = .022, p = .004, respectively) while the excess of mutant alleles in the other four regions (VEGFA rs833061, BDNF rs7929344, EPAS1 rs1867785 and rs1868085) showed that ROP severtiy was milder and eliminated the need for treatment (p < .001, p = .019, p = .017, p = .017, respectively). CONCLUSIONS: Considering the results of our study, it was seen that besides the known environmental and demographic factors in ROP pathogenesis, genetic predisposition also had an effect on the clinic and course of ROP. Polymorphisms of VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744 were found to be associated with severe ROP. More studies involving different populations cases are needed to confirm these findings and enlighten the etiology of ROP.

[Three Candida auris Case Reports from Istanbul, Turkey]. / Türkiye Istanbul'dan Bildirilen Üç Candida auris Olgusu.

Candida auris is a fungal pathogen that was first identified in 2009. Since its definition, it has spread globally and has caused life-threatening nosocomial infections. Increases in the number of immunocompromised individuals, empirical use of broad-spectrum antimicrobials and widespread use of catheterizations are the predisposing factors in the development of infection. There are problems for the identification of C.auris with the routine methods. In this case report, infections with C.auris, isolated for the first time from three patients in our hospital's intensive care units (ICU) between November 2020-January 2021, were presented. The first case was a 46-year-old male patient with laryngeal carcinoma who developed cardiopulmonary arrest during anesthesia induction in the tumor operation, and was followed up in the ICU. C.auris growth was detected in the blood and intravenous (IV) catheter tip cultures on the 66th day of admittance. Cure achieved on the 24th day under caspofungin treatment as no growth was determined. Second case was a 71-year-old female patient admitted to the emergency department with shortness of breath and general condition disorder that developed after COVID-19 infection and hospitalized in ICU with the diagnosis of pneumonia and acute renal failure. In the 16th day of admittance C.auris growth was detected in blood and from catheter tip cultures and the patient died in the 18th day. The third case was a 49-year-old male patient, followed up in ICU with the diagnosis of subarachnoid hemorrhage after he admitted to the emergency department with confusion. In the 35th day of admittance, 100000 CFU/ mL C auris growth was detected in urine culture. The patient was accepted as asymptomatic fungiuria and followed up in the ICU. It was determined that the three patients were intubated, had urinary and femoral venous catheters and were being followed under wide spectrum antibiotherapy when the growth of C.auris was detected. Isolates identified as C.auris by MALDI-TOF Microflex LT/SH Smart MS in the Medical Microbiology Laboratory were then confirmed by conventional methods and DNA sequencing in the National Mycology Reference Laboratory. Antifungal susceptibility tests were performed by broth microdilution method. Fluconazole MIC values were >256 mg/ml for all cases. Long-term survival in hospital environments, colonization on skin, resistance to disinfectants of C.auris, facilitate the spread of the fungi and resistance to antifungals lead to treatment failures. In this case report, it was aimed to draw attention to the infections with C.auris, its diagnosis and risk factors.

Advances in the diagnosis and treatment of keratoconus.

Keratoconus had traditionally been considered a rare disease at a time when the imaging technology was inept in detecting subtle manifestations, resulting in more severe disease at presentation. The increased demand for refractive surgery in recent years also made it essential to more effectively detect keratoconus before attempting any ablative procedure. Consequently, the armamentarium of tools that can be used to diagnose and treat keratoconus has significantly expanded. The advances in imaging technology have allowed clinicians and researchers alike to visualize the cornea layer by layer looking for any early changes that might be indicative of keratoconus. In addition to the conventional geometrical evaluation, efforts are also underway to enable spatially resolved corneal biomechanical evaluation. Artificial intelligence has been exploited in a multitude of ways to enhance diagnostic efficiency and to guide treatment. As for treatment, corneal cross-linking treatment remains the mainstay preventive approach, yet the current main focus of research is on increasing oxygen availability and developing new strategies to improve riboflavin permeability during the procedure. Some new combined protocols are being proposed to simultaneously halt keratoconus progression and correct refractive error. Bowman layer transplantation and additive keratoplasty are newly emerging alternatives to conventional keratoplasty techniques that are used in keratoconus surgery. Advances in tissue engineering and regenerative therapy might bring new perspectives for treatment at the cellular level and hence obviate the need for invasive surgeries. In this review, we describe the advances in the diagnosis and treatment of keratoconus primarily focusing on newly emerging approaches and strategies.

Prevalence and risk factors for keratoconus in a university-based population in Turkey.

PURPOSE: To determine the prevalence of keratoconus (KC) in the students and faculty members (aged ≥18 and ≤30 years) studying/working at the Medical and Health Sciences faculties of Eskisehir Osmangazi University. SETTING: Eskisehir Osmangazi University, Eskisehir, Turkey. DESIGN: Prevalence study. METHODS: Subjects were randomly selected to undergo KC screening using a proportional stratified sampling method. Of the 648 invited subjects, 585 (90.3%) responded to the invitation. The demographic data, medical/family history, and habits of the subjects were collected using a standardized questionnaire. Subjects were classified as KC, ectasia susceptibility, and normal based on the corneal tomography. The chi-square and Kruskal-Wallis tests were used for the analysis of categorical variables and parametric values, respectively. Risk factors for KC were determined using logistic regression analysis. RESULTS: Of the enrolled 585 subjects, the prevalence of KC was 2393/100 000 (2.4%, 95% CI: 1.3% to 4%), whereas that of ectasia susceptibility was 1538/100 000 (1.5%, 95% CI: 0.7% to 2.9%). Although the prevalence was much higher in males (4%, 95% CI: 1.7% to 7.7%) than in females (1.6%, 95% CI: 1.1% to 4.4%), the difference was not statistically significant (P = .09). Most (78.6%, n = 11) patients with KC were unaware of their disease. Eye rubbing (odds ratio [OR]: 3.53, P = .024) and consanguineous marriage (OR: 12.87, P = .032) were independent risk factors for KC. CONCLUSIONS: To the authors' knowledge, this is the first population-based KC prevalence study in a randomized sample conducted in Turkey. The prevalence of KC in Turkey was much higher than in European countries but similar to neighboring countries in the Middle East. Eye rubbing and history of consanguineous marriage were significant risk factors.

The Relationship Between Vasoproliferative Tumor and Uveitis in a Multiple Sclerosis Patient: A Case Report and Review of the Literature

Vasoproliferative retinal tumor (VPRT) is a rare, benign lesion with a variable clinical course depending on the individual. Favorable outcomes are obtained with early diagnosis and treatment of patients with VPRT. In this case report, we present a case of concomitant VPRT and multiple sclerosis along with our management of uveitis and secondary glaucoma that presumably developed following cryotherapy for VPRT.