Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review.

This literature review will provide a critical narrative overview of the highlights and potential pitfalls of the reported animal models for limbal stem cell deficiency (LSCD) and will identify the neglected aspects of this research area. There exists significant heterogeneity in the literature regarding the methodology used to create the model and the predefined duration after the insult when the model is supposedly fully fit for evaluations and/or for testing various therapeutic interventions. The literature is also replete with examples wherein the implementation of a specific model varies significantly across different studies. For example, the concentration of the chemical, as well as its duration and technique of exposure in a chemically induced LSCD model, has a great impact not only on the validity of the model but also on the severity of the complications. Furthermore, while some models induce a full-blown clinical picture of total LSCD, some are hindered by their ability to yield only partial LSCD. Another aspect to consider is the nature of the damage induced by a specific method. As thermal methods cause more stromal scarring, they may be better suited for assessing the anti-fibrotic properties of a particular treatment. On the other hand, since chemical burns cause more neovascularisation, they provide the opportunity to tap into the potential treatments for anti-neovascularisation. The animal species (i.e., rats, mice, rabbits, etc.) is also a crucial factor in the validity of the model and its potential for clinical translation, with each animal having its unique set of advantages and disadvantages. This review will also elaborate on other overlooked aspects, such as the anaesthetic(s) used during experiments, the gender of the animals, care after LSCD induction, and model validation. The review will conclude by providing future perspectives and suggestions for further developments in this rather important area of research.

Assessment of the levels of some prognostic biomolecules (galectins, ACE2, SCUBE1/2/3) in COVID-19 patients.

Aim: Our aim was to investigate the differences between healthy people and COVID-19 patients in terms of some immunological biomolecules, especially including those related to the inflammation process. Materials & methods: A total of 180 participants (90 healthy controls and 90 COVID-19 patients) were included. The expression levels of eight different inflammation-related biomolecules were measured by the ELISA technique. Results: The mean levels of ACE2, ANG1-7, GAL3, GAL9, SCUBE1, SCUBE2 and SCUBE3 were elevated in COVID-19 patients when compared with healthy controls, while the mean level of GAL2 was lower in COVID-19 patients than controls. Conclusion: To understand the cytokine storm mechanism and related parameters, more detailed studies should be performed investigating more related biomolecules and related signaling pathways.

Developing a Novel Platelet-Rich Plasma-Laden Bioadhesive Hydrogel Contact Lens for the Treatment of Ocular Surface Chemical Injuries.

Permanent injury to corneal limbal stem cells after ocular surface chemical and thermal injuries is a major cause of corneal blindness. In this study, a PRP-laden GelMA hydrogel contact lens is manufactured which is aimed to support the limbal niche after ocular surface insults thereby preventing limbal stem cell failure. GelMA with varying platelet-rich plasma (PRP) concentrations (5%, 10%, and 20%) is photopolymerized using a visible light crosslinking system followed by characterizations of mechanical properties, growth factor release, enzymatic degradation, and in vitro cytotoxicity. The addition of 10% PRP into 10% GelMA hydrogel precursor solution results in the highest tensile and compressive modulus (38 and 110 kPa, respectively) and burst pressure (251±37.66 mmHg). Degradation time varies according to the concentration of the collagenase enzyme tested (0, 2.5, 5, and 40 µg/mL) and is most prolonged with 20% PRP. EGF and TGF-ß release profiles suggest an initial burst release followed by sustained release, most consistent in the 10% PRP sample. Although cell viability decreases on day 1, rapid recovery is observed and is approximately 120% after day 21. PRP-laden GelMA in the form of a contact lens may be a promising biomaterial-based treatment approach for the maintenance of limbal epithelial stem cells after ocular surface insults.

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.

Investigation of the Role of Convolutional Neural Network Architectures in the Diagnosis of Glaucoma using Color Fundus Photography.

Objectives: To evaluate the performance of convolutional neural network (CNN) architectures to distinguish eyes with glaucoma from normal eyes. Materials and Methods: A total of 9,950 fundus photographs of 5,388 patients from the database of Eskisehir Osmangazi University Faculty of Medicine Ophthalmology Clinic were labelled as glaucoma, glaucoma suspect, or normal by three different experienced ophthalmologists. The categorized fundus photographs were evaluated using a state-of-the-art two-dimensional CNN and compared with deep residual networks (ResNet) and very deep neural networks (VGG). The accuracy, sensitivity, and specificity of glaucoma detection with the different algorithms were evaluated using a dataset of 238 normal and 320 glaucomatous fundus photographs. For the detection of suspected glaucoma, ResNet-101 architectures were tested with a data set of 170 normal, 170 glaucoma, and 167 glaucoma-suspect fundus photographs. Results: Accuracy, sensitivity, and specificity in detecting glaucoma were 96.2%, 99.5%, and 93.7% with ResNet-50; 97.4%, 97.8%, and 97.1% with ResNet-101; 98.9%, 100%, and 98.1% with VGG-19, and 99.4%, 100%, and 99% with the 2D CNN, respectively. Accuracy, sensitivity, and specificity values in distinguishing glaucoma suspects from normal eyes were 62%, 68%, and 56% and those for differentiating glaucoma from suspected glaucoma were 92%, 81%, and 97%, respectively. While 55 photographs could be evaluated in 2 seconds with CNN, a clinician spent an average of 24.2 seconds to evaluate a single photograph. Conclusion: An appropriately designed and trained CNN was able to distinguish glaucoma with high accuracy even with a small number of fundus photographs.

Biometric Determinants of Epithelial Thickness Profile Across a Wide Range of Refractive Errors.

INTRODUCTION: To evaluate the corneal epithelial thickness (CET) profiles and their correlations with axial length (AL) and anterior corneal radius of curvature (Rm F) across different refractive error groups. METHODS: A total of 1225 eyes of 616 normal patients were included. CET mapping, AL, and Rm F were obtained using spectral-domain optical coherence tomography, optical biometry, and Scheimpflug corneal tomography, respectively. In the CET map, one central (2 mm), eight paracentral (2-5 mm), and eight peripheral (5-6 mm) quadrants were evaluated separately. The subjects were divided into four groups based on their refractive status: hyperopia (spherical equivalent [SE] ≥ +0.50 D), emmetropia (SE > -0.50 D and < +0.50 D), low myopia (SE ≤ -0.50 D and > -3.0 D), and moderate-high myopia (SE ≤ -3.0 D) groups. Linear mixed model analysis with Bonferroni correction was used to compare CET according to refractive error groups. The correlations between the CET profile and the AL and Rm F were analyzed. RESULTS: The central CET was 53.7 ± 3.3 µm in hyperopia (n = 34), 53.2 ± 2.9 µm in emmetropia (n = 353), 52.8 ± 2.9 µm in low myopia (n = 677), and 52.0 ± 3.1 µm in moderate-high myopia (n = 161). Although thinning was observed in CET in all quadrants from hyperopia to moderate-high myopia, it was only significant in the superior and superonasal quadrants at the 2-5 mm and 5-6 mm-diameter rings. While AL and CET were significantly positively correlated (r range 0.17-0.28) in the moderate-high myopia group, Rm F and CET were significantly positively correlated (r range 0.08-0.10) in the low and moderate-high myopia groups. CONCLUSION: CET varied according to different refractive error groups and was positively correlated with AL and Rm F, particularly in the moderate-high myopia group.

Belin ABCD Progression Display Identifies Keratoconus Progression Earlier Than Conventional Metrics.

PURPOSE: To compare the progression rate and time to progression determined using the Belin ABCD Progression Display (BAPD) with conventional metrics in patients with keratoconus (KC). DESIGN: Retrospective comparison of progression assessment. METHODS: Patients 18 years and older and 35 years and younger with at least 1 year of follow-up and 3 Pentacam (Oculus, Inc) visits were included in the study. Progression was evaluated by selecting either the first visit or the first 2 visits individually as the baseline on the BAPD, and the red gate was used to determine progression (variability in any A, B, and C parameters ≥95% CI or any 2 parameters ≥80% CI). An increase of ≥1 diopter in corneal astigmatism and curvature parameters and a ≥2% reduction in thickness parameters constituted progressive disease. RESULTS: Two hundred seventy-seven eyes of 155 patients were included. The 2 baseline visit criteria identified the highest progression (n = 186 [67.2%]), followed by the single baseline visit (n = 158 [57%]), minimum corneal thickness (n = 114 [41.2%]), central corneal thickness (n = 111 [40.1%]), maximum keratometry (n = 76 [27.4%]), corneal astigmatism (n = 55 [19.9%]), back mean keratometry (n = 50 [18.1%]), and front mean keratometry (n = 31 [11.2%]) criteria. The median time to progression was shortest using the single baseline visit criterion (11 months), followed by the 2 baseline visits (11.6 months), minimum corneal thickness (12.1 months), maximum keratometry (12.3 months), corneal astigmatism (14.8 months), central corneal thickness (16.6 months), back mean keratometry (18.4 months), and front mean keratometry (24.4 months) criteria. In a subgroup analysis, progression could be identified 4 to 7 months earlier with the BAPD in eyes that were also progressive for maximum keratometry and central corneal thickness. CONCLUSIONS: BAPD detects progression at a higher rate and earlier than conventional parameters.

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.

Superiority of Baseline Biomechanical Properties over Corneal Tomography in Predicting Keratoconus Progression

Objectives: To determine corneal biomechanical and tomographic factors associated with keratoconus (KC) progression. Materials and Methods: This study included 111 eyes of 111 KC patients who were followed-up for at least 1 year. Progression was defined as the presence of progressive change between the first two consecutive baseline visits in any single parameter (A, B, or C) ≥95% confidence interval or two parameters ≥80% confidence interval for the KC population evaluated by the Belin ABCD progression display. The eye with better initial tomographic findings was chosen as the study eye. Analyzed Pentacam parameters were maximum keratometry (Kmax), minimum pachymetry (Kmin), central corneal thickness, thinnest corneal thickness, 90° vertical anterior and posterior coma data in Zernike analysis, and Belin Ambrosio Enhanced Ectasia Display Final D value. Corneal hysteresis (CH) and corneal resistance factor (CRF) were analyzed together with the waveform parameters obtained with Ocular Response Analyzer (ORA). Factors related to KC progression were evaluated using t-tests and logistic regression tests. Statistical significance was accepted as p<0.05. Results: There were 44 (mean age: 27.1±8.5 years, female: 25) and 67 (mean age: 31.1±9.1 years, female: 36) patients in the progressive and non-progressive groups, respectively. Although Pentacam parameters along with CH and CRF were similar between the two groups, ORA waveform parameter derived from the second applanation signal p2area was statistically significantly lower in the progressive group (p=0.02). Each 100-unit decrease in p2area increased the likelihood of keratoconus progression by approximately 30% in the logistic regression analysis (ß=0.707, p=0.001, model r2=0.27). Conclusion: Parameters derived from the second applanation signal of ORA may be superior to conventional ORA parameters and corneal tomography in predicting KC progression.

Awareness and Attitudes Toward Cornea Donation in a Turkish Population: A Web-Based Survey.

OBJECTIVES: With low supply and high demand for donor corneas, we surveyed Turkish participants on level of knowledge, awareness, and willingness toward cornea donation. MATERIALS AND METHODS: Our prepared internet-based questionnaire on awareness and attitudes toward cornea donation was structured into 6 parts (parts 1-2 examined socio-demographic data and existing chronic eye diseases, parts 3-4 evaluated level of knowledge on cornea donation and willingness to donate, parts 5-6 questioned whether level of cornea donation was sufficient within the country). For univariate analyses, the chi-square test (Fisher exact where appropriate) was used. We used stepwise logistic regression analyses to evaluate factors associated with willingness to donate (α = 0.05). RESULTS: Of 2301 surveyed participants, 980 (42.6%) claimed to have knowledge on cornea donation/ - transplantation, with 1297 (56.4%) having willingness toward donation. Bachelor level or higher education (odds ratio = 1.33, 95% CI, 1.10-1.61; P = .004); being a health care professional (odds ratio = 1.55, 95% CI, 1.21-1.97; P = .001), university student (odds ratio = 1.53, 95% CI, 1.25-1.87; P < .001), or artist professional (odds ratio = 5.25, 95% CI, 1.12-24.6; P = .05); presence of chronic eye disease (odds ratio = 1.22, 95% CI, 1.03-1.45; P = .02); and self-reported awareness of donation/transplantation (odds ratio = 2.14, 95% CI, 1.78-2.58; P < .001) were independently associated with willingness to donate. The major disclosed reason for unwillingness was "lack of knowledge" (48.5%, n = 269); the 2 most common self-perceived reasons for negative public attitudes toward cornea donation were "lack of knowledge" (84.8%, n = 1948) and "religious and cultural reasons" (55.8%, n = 1283). CONCLUSIONS: Associations between both higher education and self-reported knowledge and willingness to donate are testaments that community education can help alleviate unrealistic concerns and prejudices toward cornea donation and hence improve availability of donor corneas.

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 Effect of Medical Lowering of Intraocular Pressure on Peripapillary and Macular Blood Flow as Measured by Optical Coherence Tomography Angiography in Treatment-naive Eyes.

PRCIS: Reduction of intraocular pressure (IOP) by latanoprost in treatment-naive eyes is significantly correlated to an increase in vessel density (VD) at the optic nerve head (ONH). PURPOSE: To evaluate the effect of topical latanoprost on ocular microvasculature using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this prospective case-control study, 26 eyes from 18 treatment-naive subjects in whom prostaglandin analogue (PGA) latanoprost 0.005% was initiated were included as cases. In 10 out of the 18 subjects, medication was initiated in only 1 eye; their contralateral untreated eyes were used as controls. OCTA (AngioVue, Optovue Inc., Fremont, CA) was performed at baseline and ≥3 weeks after commencing treatment. Main outcome measures were change in flow area and VD at the ONH, radial peripapillary capillaries (RPC), and macula. Comparison between the 2 visits was performed using a linear mixed model adjusted for intereye correlation and mean ocular perfusion pressure. RESULTS: IOP decreased by 26.1%±11.3% (P<0.001) in the cases and 0.18%±12.2% (P=0.63) in controls. Significant correlations between change in IOP and change in ONH VD (correlation coefficient [r]=-0.42, P=0.04), and between change in IOP and change in RPC VD (r=-0.48, P=0.02) were observed in the cases, whereas none were observed in the controls. When multiple testing was considered, no significant changes in flow area and VD were observed in cases and controls. CONCLUSIONS: The reduction of IOP by a PGA in treatment-naive eyes was significantly correlated to the increase in ONH VD and RPC VD. This may indicate a mechanism by which IOP reduction modulates the risk of glaucoma progression by improving ocular microperfusion.

Lack of association between obstructive sleep apnea syndrome and specular microscopic features of the corneal endothelium.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of hypoxemia and hypercapnia during sleep. The aim of this study was to determine whether OSAS causes significant changes in corneal endothelium detectable by specular microscopy. METHODS: This prospective, cross-sectional study compared the specular microscopic features of the corneal endothelium of patients with OSAS and age-and gender-matched controls. Patients diagnosed with OSAS by polysomnography in the sleep unit were classified using apnea-hypopnea indexes into two groups as mild-moderate OSAS group and severe OSAS group. All participants were divided into three age groups: 30-45, 46-60, and > 60 years. Corneal endothelial cell density (ECD), percentage of hexagonal cells (Hex), and coefficient of variation of cell area (CV) were obtained using a non-contact specular microscope. The measurements of each group were compared statistically. RESULTS: A total of 66 patients (51.1 ± 9.4 years) and 88 controls (49.2 ± 10.5 years) were examined. The mild-moderate OSAS group and the severe OSAS group had no significant differences in measures of specular microscopy compared with the controls (ECD, p = 0.84; Hex, p = 0.18; CV, p = 0.41). The mean values of ECD, Hex, and CV were 2552.56 ± 302.49 cells/mm2, 54.13 ± 8.13%, and 36.41 ± 5.92, respectively, in the mild-moderate OSAS group; 2510.52 ± 377.12 cells/mm2, 54.85 ± 8.68%, and 34.77 ± 5.02, respectively, in the severe OSAS group; 2543.37 ± 286.94 cells/mm2, 51.89 ± 9.09%, and 36.03 ± 5.32, respectively, in the control group. CONCLUSIONS: There were no significant differences in corneal endothelial features between patients and controls. Although OSAS causes systemic hypoxia, its effects do not appear to result in corneal endothelial alterations detectable by specular microscopy.

Effect of isotretinoin on myopia and axial length: a pilot study.

PURPOSE: To investigate the effect of oral isotretinoin use on refractive error, axial length, and anteroposterior segment parameters. MATERIALS AND METHODS: In this prospective study, 50 eyes of 50 patients using isotretinoin with a diagnosis of acne vulgaris and 50 eyes of 50 healthy control subjects were included. After detailed biomicroscopy, measurements were taken of axial length, lens thickness, central corneal thickness, anterior chamber depth, central retinal thickness, and subfoveal choroidal thickness. The pupils of both eyes were dilated with one drop of cycloplegic drops after refraction measurement. Visual acuity examination was performed with a Snellen chart the next day. The same procedure was repeated at the end of the third and sixth month of drug treatment. RESULTS: Forty-seven patients with acne vulgaris and 45 healthy controls met the inclusion criteria and were included in the analysis. The mean ages of the patients and the controls were 21.7 ± 2.5 years (range, 18-28 years) and 22.6 ± 2.7 years (range, 19-27 years), respectively. No significant changes were observed in any parameters in the third and sixth month in the control group (p > 0.05). The most important result was significant increases in myopia and axial length in the sixth month of isotretinoin use (p = 0.01, p = 0.04, respectively). There were no significant relationships between increases in myopia and axial length and patients' age, sex, drug dose, and initial refraction (p > 0.05). The changes in spherical equivalent and axial length differed significantly between the drug group and the control group (p = 0.001, p = 0.001, respectively). CONCLUSIONS: Isotretinoin is one of the important molecules in the aetiology of myopia. Oral isotretinoin treatment may increase myopia and axial length, although not to a clinically significant degree. However, as this was a pilot study, there is a need for further studies with more patients and longer follow-up periods.

The Influences of Metformin on Prostate in Terms of PSA Level and Prostate Volume.

PURPOSE: The effects of metformin on prostate volume and prostate-specific antigen (PSA) were investigated. MATERIALS AND METHODS: We enrolled 384 newly diagnosed diabetes mellitus (DM) patients and 152 controls all of whom were >50 years into our prospective cross-sectional observational study. The first group contained patients receiving metformin only, the second group patients were taking a mixture of medications, including metformin plus other oral anti-diabetics, and the third was the control group. Before beginning treatment, body mass indices (BMI) of all cases were obtained. Prostate volumes were evaluated using transabdominal ultrasonography at the sixth and twelfth months. Insulin, glycosylated hemoglobin (HbA1C), insulin sensitivity index (ISI), insulin-rich growth factor (IGF-1), PSA, free PSA, and total testosterone levels were measured. RESULTS: The differences in BMI between the first and third groups were statistically significant (P < 0.05). There were no statistical differences among the groups in terms of prostate volumes (P > 0.05). The differences between the groups for insulin, HbA1C, ISI, IGF-1 (somatomedin), PSA, free PSA, and total testosterone levels were not statistically significant (P > 0.05). Free PSA and total testosterone levels in groups 1 and 2 were not statistically different at the beginning of treatment and the sixth month (p >0.05), but within groups 1 and 2, only PSA levels were different at the start of the study until completion. No differences were seen in the third group. CONCLUSION: Metformin appears to cause a decrease in PSA levels. The mechanism and any effects on prostate tissue will be studied in future randomized, prospective studies.

Distribution of Microbial Keratitis After Penetrating Keratoplasty According to Early and Late Postoperative Periods

Objectives: The aim of this study was to investigate the distribution of microbial agents in the early and late postoperative periods in patients with microbial keratitis (MK) after penetrating keratoplasty (PK). Materials and Methods: The records of 36 patients who were clinically diagnosed as having MK after PK were retrospectively reviewed. Culture results were obtained from microbiology records and the organisms that were produced were noted. A case was deemed as viral keratitis based on the clinical appearance, negative cultures, and response to antiviral treatment. Keratitis development times were evaluated in 2 categories: early (within the first year) and late (after year 1) postoperative period. Mann-Whitney U and Kruskal-Wallis tests were used to compare numerical variables that did not show normal distribution and chi-square test was used to compare categorical variables. Results: The majority of MK cases were of bacterial origin (55.5%, n=20), followed by viral (41.7%, n=15) and fungal (2.8%, n=1). Of the 15 cases of early postoperative MK, 10 were bacterial, 4 were viral, and 1 was fungal; however, among cases of late postoperative MK, 10 were bacterial and 11 were viral. The majority (65%) of early and late bacterial infections were caused by gram-positive strains (most commonly staphylococci). Gram-positive bacteria caused keratitis significantly earlier than gram-negative bacteria (p=0.037). Viral and gram-negative bacterial MK was more frequent in the late postoperative period, but the difference was not statistically significant. Conclusion: In our study, bacterial keratitis was more common in post-keratoplasty MK than viral and fungal keratitis. Gram-positive bacteria were the most common causative agents. The increased incidence of gram-negative bacterial agents and viral keratitis in the late postoperative period can be explained by long-term topical steroid use.

Optical coherence tomography angiography analysis of fabry disease.

PURPOSE: Fabry disease (FD) is characterized by a deficiency in α-galactosidase A activity that leads to the cumulative deposition of unmetabolized glycosphingolipids within organs, including the vascular endothelium and the eyes. The purpose of this study was to assess the effects of FD on the retinal microvasculature, foveal avascular zone (FAZ), macular thickness and retinal nerve fiber layer (RNFL) using optical coherence tomography angiography (OCT-A). METHODS: Twenty-five patients (14 female and 11 male; mean age 33.16 ± 11.44) with genetically verified FD were compared with 37 age- and sex-matched healthy controls (mean age 32.36 ± 15.54). The vessel density (VD) values of the superficial and deep capillary plexuses (SCP and DCP), the area of the FAZ, the density of radial peripapillary capillaries (RPC), the macular thickness and the retinal nerve fiber layer thickness were measured by OCT-A examination. RESULTS: The patients showed significantly lower VD values than controls in the foveal regions of both SCP and the DCP (21.15 ± 5.56 vs. 23.79 ± 4.64 (p = 0.048), 37.92 ± 6.78 vs. 41.11 ± 5.59 (p = 0.048), respectively). The FAZ was significantly larger in the FD group than in the control group (0.3 ± 0.1 vs. 0.24 ± 0.08 (p = 0.011)). No significant difference was identified in measurements of RPC density, peripapillary RNFL thickness or macular thickness between the two groups (p > 0.05 for all). CONCLUSION: Decreased VD and an enlarged foveal avascular area suggest possible changes in the retinal microvasculature of patients with FD. OCT-A can serve as a useful, noninvasive, quantitative tool for diagnosing FD and monitoring its progression.

Systemic and ocular determinants of mean ocular perfusion pressure in a population-based sample.

PURPOSE: To investigate the associations between mean ocular perfusion pressure (MOPP) and several variables including body mass index (BMI), comorbid medical conditions and various ocular parameters in a population-based sample. STUDY DESIGN: Cross-sectional. METHODS: Data of 2091 healthy participants from a previous population based cross-sectional study were reviewed. Inclusion criteria were adults ≥40 years of age who were screened on-site for glaucoma. Data on medical history, height, weight, systolic and diastolic blood pressures (SBP and DBP, respectively) were obtained. A basic ocular examination was performed which included intraocular pressure (Tono-Pen XL, Reichert Technologies) and central corneal thickness (Pacline pachymetry;) measurement, slit-lamp examination and non-mydriatic optic disc photography (nonmydα fundus camera, Kowa). MOPP was calculated using the formula [2/3 x (DBP + 1/3(SBP-DBP)]-IOP and low MOPP was defined as MOPP ≤45 mmHg. RESULTS: Mean age of the subjects was 63.04 ± 9.7 years (range: 44 and 99 years) and the majority were women (74.1%, n = 1549). Mean MOPP values in normal weight (BMI < 25), overweight (BMI = 25-29.9) and in obese individuals were 46.9 ± 9.0 mmHg, 48.6 ± 9.2 mmHg and 50.7 ± 10.0 mmHg, respectively (p < 0.001, in all pairwise comparisons). In the multivariable logistic regression analysis, migraine and IOP elevation (per 1 mmHg increment) were significantly associated with a low MOPP (OR: 2.10 and 1.22, p = 0.008 and < 0.001, respectively). On the other hand, risk of low MOPP was reduced in subjects with hypertension, and with increasing age (per 1-year increment) and BMI (per 1-unit increment) (OR: 0.15, 0.97, and 0.95, respectively, and p < 0.001 for all). CONCLUSION: Migraine and elevated IOP increase the risk of low MOPP and this may have a causal relationship with impaired optic nerve head blood flow.

The influence of corneal geometrical and biomechanical properties on tonometry readings in keratoconic eyes.

PURPOSE: To identify the effect of corneal geometrical and biomechanical parameters on the intraocular pressure (IOP) measurements obtained by Goldmann Applanation Tonometer (GAT), non-contact tonometer, iCare Pro Rebound Tonometer (IRT), Tonopen and Ocular Response Analyzer (ORA, Goldmann-correlated IOP: IOPg, corneal compensated IOP: IOPcc). METHODS: We prospectively recruited patients with a tomographically confirmed diagnosis of keratoconus. IOP measurements were performed in the following order: non-contact tonometry, ORA, IRT, GAT and Tonopen. The means of the three IOP measurements were used for the analysis. Correlation analyses were performed to assess the association between tonometer readings and the corneal geometrical and biomechanical parameters including ORA waveform parameters. Tonometer variability was assessed using a stepwise linear regression analysis. RESULTS: Fifty-one patients with keratoconus (27 females, mean age 30.8 ± 8.7 years) were evaluated. The highest mean IOP was measured by IOPcc (14.6 ± 2.3 mmHg) followed by IRT IOP (13.0 ± 3.2 mmHg), Tonopen IOP 12.0 ± 2.6 mmHg), GAT IOP (11.7 ± 3.1 mmHg), NCT IOP (10.2 ± 3.2 mmHg) and IOPg (10.2 ± 3.6 mmHg). NCT and IOPg were affected from all corneal parameters including thickness, curvature and biomechanical parameters. While GAT and IRT had significant correlations with corneal resistance factor (CRF) and corneal hysteresis, IOPcc only had a significant correlation with CRF. None of the corneal factors had any statistically significant correlation with Tonopen. CRF predicted tonometer measurement variability in 7 of the 15 inter-device variability assessments. CONCLUSION: Tonopen was the least affected from the corneal parameters followed by IOPcc and GAT. CRF was a strong determinant of tonometer variability.