Protective Effect of Vaccinium myrtillus Extract on X-ray Irradiation-Induced Retinal Toxicity via eNOS and 8-OHdGexpression.

Every year, hundreds of thousands of cancer patients receive radiotherapy treatment. Oxidative stress is observed in healthy tissues due to irradiation exposure. The present study is the first to address the effects of Vaccinium myrtillus (whortleberry, WB) against the effects of x-ray irradiation on retinal tissue. Twenty-four Sprague-Dawley rats were randomly allocated into 4 groups: (1) control group: rats without any treatment, (2) x-ray irradiation group: 8 Gray (Gy) RT for 2 days, (3) 100 mg WB extract + x-ray irradiation group: 8 Gy irradiation for 2 days and followed by intraperitoneal (IP) WB extract (100 mg/kg) supplementation for 10 days, (4) 200 mg WB extract + x-ray irradiation group: 8 Gy irradiation for 2 days and followed by intraperitoneal (IP) WB extract (200 mg/kg) supplementation for 10 days. Eyes were enucleated on the 10th day after RT for histopathological, immunohistochemical (8-hydroxy deoxyguanosine (8-OHdG), endothelial nitric oxide synthase (eNOS), and biochemical analyses (glutathione peroxidase (GSH), and malondialdehyde (MDA). The GSH levels significantly decreased and MDA levels and 8-OHdG staining increased after x-ray irradiation compared to the control group. Combined x-ray irradiation +WB treatment significantly increased GSH levels and significantly decreased MDA production and 8-OHdG staining. However, eNOS staining was not affected in any of the groups. Besides, x-ray irradiation significantly increased cell losses and edematous areas. The WB significantly reversed the cellular damage in ganglion cells, inner nuclear, and outer nuclear layers in quantitative analyses. The x-ray irradiation caused significant retinal impairment, and additional WB therapy provided protective effects against radiation-induced retinopathy. These results may suggest WB extract as an adjuvant therapy to reverse retinal impairments after x-ray irradiation.

Increased serum concentration of netrin-1 after intravitreal bevacizumab injection: is it a compensatory mechanism to counteract drug side effects?

BACKGROUND: To evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME). METHODS: This prospective case-control study included a total of 50 participants assigned to one of three groups, including 10 individuals with DME and non-proliferative diabetic retinopathy (NPDR), 13 with DME, and proliferative diabetic retinopathy (PDR), and 27 healthy individuals as a control group. Serum VEGF and netrin-1 concentrations were measured by enzyme-linked immunosorbent assays (ELISAs) immediately before, as well as 1 week and 1 month after, intravitreal BCZ injection. RESULTS: The mean VEGF serum concentrations in the PDR and NPDR groups were 388.4 and 196.9 pg/mL at baseline, respectively. After 1 week, these concentrations changed to 193.41 and 150.23 pg/mL, respectively (P = 0.001 and P = 0.005, respectively); after 1 month, the concentrations were 97.89 and 76.46 pg/mL, respectively (P = 0.001 and P = 0.009, respectively). The mean netrin-1 serum concentrations in the PDR patients and NPDR groups were 318.2 and 252.7 pg/mL at baseline, respectively. After 1 week, these concentrations increased to 476.6 and 416.3 pg/mL, respectively (P = 0.033 and P = 0.005, respectively), and after 1 month, they were 676.6 and 747.5 pg/mL, respectively (P = 0.001 and P = 0.005, respectively). The correlation analysis revealed a significant inverse relationship between changes in serum VEGF and netrin-1 concentrations in both the PDR and NPDR groups (r = - 0.685, P = 0.029). CONCLUSIONS: Intravitreal BCZ injections work systemically to significantly decrease serum VEGF levels, leading to a significant upregulation in the concentration of another angiogenic mediator, netrin-1.

The efficiency and safety of oxygen-supplemented accelerated transepithelial corneal cross-linking.

PURPOSE: To investigate the impact of oxygen delivery on the clinical outcomes of accelerated transepithelial corneal cross-linking (A-TE CXL). METHODS: Fifty-seven eyes of 44 progressive keratoconus (KCN) patients were randomly separated into two age-sex-matched groups. Twenty-nine eyes of 23 KCN patients that underwent oxygen-supplemented A-TE CXL formed the study group and 28 eyes of 21 patients treated with the same procedure but under room air conditions formed the control group. All patients were examined preoperatively, one, six and twelve months after the procedure. The logMAR spectacle-corrected distance visual acuity (CDVA), maximum keratometry (Kmax), mean keratometry, apical posterior keratometry, cylindrical power, minimum central corneal thickness, keratoconus vertex front and back, ocular aberrations, endothelial cell density (ECD), demarcation line depth (DLD) and proportion measures were recorded for statistical analysis. RESULTS: The preoperative, 1st, 6th and 12th months mean Kmax values of the study group were 55.14 ± 3.99D, 54.85 ± 3.82D, 54.37 ± 3.84D and 54.40 ± 3.86, respectively, and 54.47 ± 3.17D, 54.52 ± 2.97D, 54.25 ± 2.95D and 54.20 ± 2.97 in the control group. The mean Kmax value was decreased significantly more in the oxygen-supplemented group after 12 months compared to the control group (p = 0.019). The mean DLD was also significantly deeper in the study group (320 ± 17 µm) compared to the control group (269 ± 19 µm). There was no significant difference between the two groups in terms of ECD alterations at any of the time intervals (p > 0.05). CONCLUSION: Keratoconus progression was significantly halted in both groups 12 months after the treatment. In addition, oxygen supplementation during A-TE CXL further significantly increased clinical outcomes compared to room air conditions without any significant change in ECD measures.

The impact of hybrid contact lenses on keratoconus progression after accelerated transepithelial corneal cross-linking.

PURPOSE: To investigate the effect of hybrid contact lenses (HCLs) on keratoconus (KCN) progression after accelerated transepithelial cross-linking (A-TE CXL). METHODS: Thirty-five eyes of 26 patients who preferred Ultrahealth HCLs for an optical correction after A-TE CXL formed the study group, and 45 eyes of 34 patients who preferred spectacle correction were age- and sex-matched to form the control group. Corrected distance visual acuity (CDVA), maximum keratometry, mean keratometry, apical posterior keratometry, cylindrical power, minimum corneal thickness, keratoconus vertex indices and curvature asymmetry indices obtained by Scheimpflug corneal topography were compared before, 6 and 12 months after the procedure. Anterior segment optic coherence tomography (AS-OCT) was performed to measure the apical corneal clearance of HCL-wearing patients. RESULTS: The median pre-CXL CDVA value of the patients in the HCL group was logMAR 0.30 (0.20-1.0), and it was logMAR 0.30 (0.10-1.0) in the spectacle-corrected group. There was a significant increase in CDVA 6 and 12 months after CXL procedure in both groups (p < 0.001, 0.003, respectively). The median front curve asymmetry index (FCAsym) significantly improved after A-TE CXL in the HCL group. The pre-CXL and 12th-month topographic comparisons of the spectacle-corrected group revealed no significant difference. In addition, no significant difference was observed between topographic alterations of two groups (p > 0.05). CONCLUSION: The CDVA significantly improved, and KCN progression was halted in patients wearing HCL 12 months after A-TE CXL. Besides, FCAsym indices can be considered for follow-up of the HCL-wearing patients as an assistive parameter to AS-OCT measurements.

Pupillometry measurement and its relationship to retinal structural changes in children with attention deficit hyperactivity disorder.

PURPOSE: This study aims to assess the pupillometry measurements of the attention deficit hyperactivity disorder (ADHD) patients and to investigate their correlations with macular and RNFL thickness parameters by comparing the values with a healthy control group. METHODS: Newly diagnosed ADHD patients in a child and adolescent clinic of a tertiary hospital were consulted in an ophthalmology clinic. All participants had undergone a standard ophthalmological examination including refractometry, best corrected visual acuity, color vision, anterior segment biomicroscopy, fundoscopy, pupillometry, and OCT. All results were compared with a healthy control group at the same age. RESULTS: The study group consisted of 32 patients and there were 43 children in the control group. Mean pupillary velocities of ADHD patients and control group were 0.60 ± 0.11 mm/s and 0.63 ± 0.11 mm/s, and 0.49 ± 0.12 mm/s and 0.50 ± 0.10 mm/s, for right and left eyes, respectively. The difference was statistically significant for both eyes (p < 0.05). Mean RNFL thickness measurements of the study group were 90.69 ± 8.58 µm and 89.63 ± 8.14 µm for right and left eyes, respectively and those were 87.35 ± 7.67 µm and 88.77 ± 7.44 µm, respectively in the healthy group. Correlation between right pupillary velocity and RNFL thickness was statistically significant (r = 0.339, p = 0.003). CONCLUSION: Higher pupillary velocity values were observed in both eyes of children with ADHD and that was positively correlated with RNFL measurements of their right eyes.

The relation between retrobulbar blood flow and posterior ocular changes measured using spectral-domain optical coherence tomography in patients with obstructive sleep apnea syndrome.

PURPOSE: To investigate the effect of posterior ocular hemodynamics on the retinal nerve fiber layer (RNFL), choroid thickness (CT) and central macular thickness (CMT) in patients with obstructive sleep apnea syndrome (OSAS) and to reveal the association with glaucomatous optic neuropathy. METHODS: The research was planned as a prospective, randomized study. The ophthalmic, retinal and posterior ciliary artery pulsatile index (PI) and resistive index (RI) were measured by colored Doppler sonography. RNFL thickness, CMT and CT were then measured by spectral-domain optical coherence tomography. RESULTS: Sixty subjects were divided into four groups-mild, moderate and severe OSAS and a control group. There were 16 subjects in the control group, 14 in the mild OSAS group, 15 in the moderate OSAS group and 15 in the severe OSAS group. Ophthalmic artery and central retinal artery PI and RI values of the OSAS patients did not show statistically significant difference than those of the control group, but posterior ciliary artery (PCA) PI and RI values were significantly higher. In addition, mean, superior and inferior RNFL thickness values were significantly lower than those in the control group. Moreover, the glaucoma prevalence of the OSAS patients in this study was 6.8% and all of these patients were in the severe OSAS group. CONCLUSION: PI and RI values of the PCA, which supplies the optic nerve, show a linear increase as the apnea hypoxia index values in OSAS. As the grade of OSAS improves, this situation leads to a more serious ischemic optic neuropathy. Furthermore, the prevalence of glaucoma in this study is found to be higher in the severe OSAS group.

Retinal nerve fiber layer and ganglion cell layer thickness in patients receiving systemic isotretinoin therapy.

To evaluate the effect of oral isotretinoin therapy on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by spectral domain optical coherence tomography (OCT). This prospective study included newly diagnosed nodulocystic acne patients about to receive isotretinoin treatment. Macular average GCL thickness and peripapillary average, temporal, nasal, inferior, and superior quadrant RNFL thickness were measured by OCT before and after isotretinoin treatment. Pre- and post-treatment measurements were compared with paired t test. Fifty-six eyes of 28 patients were included. The mean duration of the treatment was 6.5 ± 1.3 months. The mean average GCL thickness was 90.04 ± 5.87 (80-96) µm at baseline and 90.75 ± 6.34 (81-96) µm after treatment. The mean average RNFL thickness was 93.25 ± 6.06 µm (84-107) before treatment and 93.05 ± 5.54 µm (82-106) after treatment. There were no statistically significant differences between pre- and post-treatment values (all p > 0.05). A 6-month course of systemic isotretinoin therapy seems to have no unfavorable effect on retinal ganglion cells; however, larger studies with longer follow-up periods are needed to be conclusive.

Evaluation of tear parameters and meibomian gland morphology in keratoconus patients after epithelial-on corneal cross-linking.

PURPOSE: To evaluate the variations in tear parameters and meibomian gland morphology after epithelial-on (epi-on) corneal collagen cross-linking (CXL) in keratoconus (KC) patients. METHODS: This prospective observational study included 38 KC eyes that underwent epithelium-on CXL. Thirty-three eyes of 33 stable KC patients with no prior CXL treatment formed the KC group and 35 eyes of 35 healthy volunteers were recruited as the control group. All participants were evaluated by Schirmer I test, first and average noninvasive tear break-up time (NITBUT), ocular surface disease index (OSDI) questionnaire, and meibography scores. The CXL patients were evaluated preoperatively and at the 1st, 3rd, and 6th months, and participants without any intervention (KC and control groups) were evaluated initially, at 1st, 3rd, and 6th months. RESULTS: The KC patients had significantly lower average NITBUT, higher OSDI scores, and impaired meibomian gland morphology than healthy individuals (NITBUT(seconds): KC, 12.8(2.4-17.6), healthy group (HG), 17.1(6.8-17.6); p = 0.012, OSDI: KC, 27.5(0.0-87.5), HG, 7.5(0.0-55.0); p < 0.001, p < 0.001, respectively). A significant difference was found in Schirmer values of the CXL group at 0-1st months, first NITBUT values at 1-6 months, and average NITBUT values at 1-3 and 1-6 months (p = 0.003, p = 0.001, p = 0.003, p = 0.001, respectively). All meibography parameters remained unchanged after CXL over a 6-month follow-up compared to initial measurements. CONCLUSIONS: Even though the KC patients had lower NITBUT, higher OSDI scores, and increased meibomian gland disfunction, the CXL treatment did not significantly affect tear quantity, dry eye symptoms, and meibomian gland morphology.

Transcanalicular Multidiode Laser Versus External Dacryocystorhinostomy in the Treatment of Acquired Nasolacrimal Duct Obstruction.

OBJECTIVES: This study was a comparison of the outcomes of transcanalicular multidiode laser dacryocystorhinostomy (TCLDCR) and external dacryocystorhinostomy (EXDCR) treatment for patients with acquired nasolacrimal duct obstruction. METHODS: Thirty-one consecutive patients who underwent TCLDCR (TCLDCR group) and 68 consecutive patients who underwent EXDCR (EXDCR group) due to acquired nasolacrimal duct obstruction were enrolled in the study. Follow-up visits were performed on the first day, and at the first week, first month, third month, sixth month, and every six months thereafter. Surgical success was defined as achievement of a patent osteotomy and a successful bicanalicular silicone intubation during the procedure. Anatomical success was defined by observation of a patent osteotomy on lacrimal irrigation, regardless of epiphora. The surgery time and intra- and postoperative complications were noted for each patient. RESULTS: The TCLDCR group had a significantly shorter mean surgery time (27.9±5.5 minutes) compared with the EXDCR group (58.5±12.0 minutes) (p<0.001). However, the mean anatomical and functional rates of TCLDCR (58.0% and 54.8%, respectively) were significantly lower than those of the EXDCR group (94.1% and 91.1%, respectively) (both p<0.001). Two patients had "cheese wiring" damage of the lower canaliculus and 1 patient in the TCLDCR group had a full-thickness skin defect in the medial canthal region. No serious intra- or postoperative complication occurred in the EXDCR group. CONCLUSION: Although a TCLDCR procedure decreased the surgical time, it had a significantly lower success rate in the treatment of acquired nasolacrimal duct obstruction compared to EXDCR. The decision of the type of surgery should be made based on the cosmetic and success expectations of the patients and the presence of systemic problems.

Serum 25-Hydroxy Vitamin D, Vitamin B12, and Folic Acid Levels in Progressive and Nonprogressive Keratoconus.

PURPOSE: To evaluate the serum 25-hydroxy vitamin D, vitamin B12, and folic acid (FA) levels in progressive and nonprogressive patients with keratoconus (KCN). METHODS: Fifty-five patients with KCN (28 progressive and 27 nonprogressive) who were followed up for at least 12 months were recruited and separated into 2 groups according to corneal topographic progression criteria. Age- and sex-matched 30 healthy individuals formed the control group. Serum vitamin D, B12, FA, and Ca levels were compared among control, nonprogressive, and progressive groups. The effect of gender, age, vitamin D, B12, and FA parameters on KCN progression was investigated. RESULTS: Serum vitamin D levels were 12.77 ± 5.52, 11.78 ± 4.32, and 17.40 ± 5.12 ng/mL in nonprogressive, progressive, and control groups, respectively. The serum vitamin D levels in KCN groups (nonprogressive and progressive) were significantly lower than the control group (P = 0.002 and P < 0.001, respectively). There was no significant difference between all groups in serum vitamin B12, FA, and Ca levels (P > 0.05). Decreased vitamin D levels significantly increased nonprogressive KCN probability 1.23 times and progressive KCN probability 1.29 times more than the control group (P = 0.002, 95% confidence interval, 0.708-0.925; P < 0.001, 95% confidence interval, 0.668-0.888, respectively). CONCLUSIONS: Serum vitamin D levels were significantly decreased in both KCN groups. However, serum vitamin B12, FA, and Ca levels were similar in all groups. Serum vitamin D evaluation of patients with KCN at onset and follow-up examinations may help to predict the course of the disease.

Evaluation of Personality Features and Mental State of Keratoconus Patients.

Objectives: Keratoconus (KCN) is a disorder that usually appears during adolescence and progressively reduces visual acuity. KCN may lead to differences in personality features as a result of vision loss and the numerous clinical examinations and treatment methods used from a young age. The aim of this study was to better understand the psychological characteristics of KCN patients and to define possible correlations between corneal topographic parameters and psychological state. Methods: A total of 59 KCN cases were included in the study group and were compared with 65 age- and sex-matched healthy individuals. All of the participants underwent a routine ophthalmic examination that included corrected distance visual acuity (CDVA), biomicroscopy, and fundoscopy. The KCN patients were evaluated busing Scheimpflug corneal topography. Psychiatric evaluations were performed using the Eysenck Personality Questionnaire Revised-Short Form (EPQ), the Self-Confidence Scale, the Maudsley Obsessive-Compulsive Inventory (MOCI), and the Beck Depression Inventory (BDI). Results: The mean age of the case and control groups was 23.98±5.7 years and 25.82±5.4 years, respectively. The KCN cases had significantly higher EPQ neuroticism subscale scores; higher MOCI subscale scores, with the exception of the doubting subscale; and higher BDI scores. Analysis of the KCN duration revealed a positive correlation with the checking and slowness subscales of the MOCI, however, there was no significant correlation between the psychometric scale scores, corneal topographic parameters, and CDVA. Conclusion: A substantially asymmetrical course and a relatively long period for KCN to result in severe vision loss might explain the lack of correlations between psychological parameters and visual acuity. Nonetheless, the apparent effect of vision loss on emotional distress cannot be disregarded; the day-to-day progressive loss of visual acuity and multiple, costly interventions may initiate or contribute to a depressive mood in KCN patients. A vicious depressive cycle and the exhaustion of long-term coping mechanisms might be underlying factors for the higher neuroticism scores seen among KCN patients. Both the personality traits and mental state of KCN patients demonstrate distinguishing properties; clinicians working with these patients should consider their mental state in addition to other factors in order to achieve better treatment outcomes.

Epicardial fat thickness is associated with retinopathy in patients with newly diagnosed hypertension.

OBJECTIVE: Hypertensive retinopathy develops based on endothelial dysfunction, inflammation, and atherosclerosis. Epicardial fat secretes various cytokines associated with endothelial dysfunction, oxidative stress, inflammation, and atherosclerosis. We aimed to evaluate whether epicardial adipose tissue (EAT) thickness is a marker for retinopathy in newly diagnosed hypertensive patients. METHODS: A total of 73 newly diagnosed hypertension (HT) patients were included in the study. Transthoracic echocardiography (TTE) was used to measure EAT thickness. To evaluate the presence of retinopathy in HT patients, hypertensive retinopathy staging was performed by ophthalmologists, according to Scheie classification. RESULTS: Retinopathy was detected in 27 (37.0%) of 73 patients. EAT thickness in HT patients with retinopathy was higher than the group without retinopathy (5.07±1.45 mm vs. 4.19±1.20 mm, p=0.007). Low-density lipoprotein cholesterol (LDL-C) levels in HT patients with retinopathy were higher than the group without retinopathy (162.4±41.2 mg/dl vs. 138.1±35.6 mg/dl, p=0.010). As a result of the regression analysis, LDL-C (OR=1.016, 95% CI 1.001-1.031, p=0.043) and EAT thickness (OR=1.674, 95% CI 1.069-2.626, p=0.043) were the independent predictors of retinopathy. CONCLUSION: Increased EAT thickness is associated with the presence of retinopathy in hypertensive patients.

Is Netrin-1 Deficiency Responsible for Inflammation and Systemic Diseases Related to Pseudoexfoliation?

PRECIS: Serum netrin-1 levels are significantly lower in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PEG) compared with the control group. PURPOSE: To investigate serum netrin-1 levels in PES and PEG patients and to determine the relevance of this molecule in the etiopathogenesis of PES-related and PEG-related diseases. MATERIALS AND METHODS: This prospective study included 29 PES and 17 PEG patients in the study groups and age-sex matched 47 cataract patients without pseudoexfoliative accumulation as a control group. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum netrin-1 level was significantly lower in the PES and PEG groups compared with the control group (P=0.007). Multinominal logistic regression analysis was performed in terms of netrin-1 levels ≤712.9 pg/mL, >712.9 pg/mL and sex which may affect PES and PEG. It were found that netrin-1 was a significant negative predictor for PES (odds ratio, 3.45; 95% confidence interval, 1.230-9.716; P=0.019) and PEG (odds ratio, 3.57; 95% confidence interval, 1.008-12.669; P=0.049), respectively. CONCLUSIONS: Decreased serum netrin-1 levels were detected in PES and PEG patients, similar to atherosclerosis and Alzheimer disease. Inflammation lays behind in the common pathogenesis of these diseases. Therefore, netrin-1 promises a potential anti-inflammatory role.

The acute effects of single cup of coffee on ocular biometric parameters in healthy subjects.

PURPOSE: To evaluate ocular biometric changes in healthy subjects after caffeine consumption from a cup of coffee. METHODS: A total of 36 subjects were included in this prospective observational study. Axial length (AL) and anterior segment parameters including aqueous depth (AD), anterior chamber depth (ACD), lens thickness (LT), and central corneal thickness (CCT) were measured with optic biometry, Lenstar LS 900 (Haag-Streit, Inc., Koeniz, Switzerland) before and 1 and 4 h after ingesting a cup of coffee (60 mg caffeine/100 mL). RESULTS: Mean age of the participants was 30.05 ± 7.43 years (range, 19-45). At baseline, 1st, and 4th hour, AL values were 23.9 ± 1.04 mm, 23.91 ± 1.04 mm, and 23.89 ± 1.04 mm, respectively, and no significant difference was observed (P>0.05). At baseline, 1st, and 4th hour, AD values were 3.06 ± 0.3 mm, 3.11 ± 0.3 mm, and 3.09 ± 0.3 mm, and ACD values were 3.6 ± 0.32, 3.66 ± 0.31, and 3.64 ± 0.31, respectively. AD and ACD values were significantly greater than baseline at 1st and 4th hours following coffee ingestion. Coffee intake caused a significant reduction in LT, compared with baseline and at the 1st and 4th hours which were 3.76 ± 0.28 mm, 3.69 ± 0.32 mm, and 3.72 ± 0.27 mm, respectively. No statistically significant difference was determined in between the 3 measurements in terms of CCT (P>0.05). CONCLUSION: Caffeine causes a significant increase in AD and ACD and a significant decrease in LT following oral intake, for at least 4 h.