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.

Evaluation of serum semaphorin 3A and interleukin 6 levels in patients with pseudoexfoliation syndrome.

PURPOSE: To evaluate serum semaphorin 3A (Sema3A) and interleukin 6 (IL-6) levels in pseudoexfoliation syndrome (PXS) patients to determine whether these mediators play a role in the systemic manifestations of PXS. METHODS: This prospective case-control study included 70 patients divided into PXS (n = 30) and a control group (n = 40). Serum Sema3A and IL-6 levels were analyzed using the enzyme-linked immunosorbent assay. RESULTS: The PXS group had a statistically higher IL-6 level [3.6(0.64-100) pg/mL], compared to the control group [2.1(0.41-39.93) pg/mL] (p < 0.05). On the other hand, the Sema3A level of the PXS group was lower at [21.55(13.2-67.5) ng/mL] compared to the control group at [29.05(11.5-103.3) ng/mL] (p < 0.05). In the PXS group, there was no correlation between the participants' IL-6 values and Sema3A, age, and body mass index (BMI) (r = 0.153, 0.000, - 0.103, respectively, all, p > 0.05), and between Sema3A values and age and BMI values (r = 0.048, - 0.133, respectively, all, p > 0.05). In the control group, there was no correlation between the participants' IL-6 values and Sema3A, age, and BMI values (r = 0.138, - 0.001, - 0.145, respectively, all, p > 0.05) and between the Sema3A and age and BMI values (r = - 0.078, - 0.281, respectively, all, p > 0.05). CONCLUSIONS: Decreased levels of the anti-inflammatory mediator Sema3A and increased levels of inflammatory mediator IL-6 detected in PXS suggest that these molecules may play a role in systemic manifestations of this syndrome, such as inflammation, atherosclerosis, heart arrhythmia, and Alzheimer's disease.

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 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.

Direct and crossover effects of brinzolamide, betaxolol, and latanoprost on choroidal thickness.

PURPOSE: To investigate the acute effects of brinzolamide, betaxolol, and latanoprost (drugs commonly used in the medical management of glaucoma) on choroidal thickness using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: Ninety healthy volunteers were evaluated in this prospective study. Participants were randomly divided into 3 groups. Brinzolamide, betaxolol, and latanoprost were administered into the left eyes of the first group (n = 30), second group (n = 30), and third group (n = 30), respectively, and artificial tear (Sodium hyaluronate) was instilled into the right eyes of all participants. Subfoveal choroidal thickness (SFCT) was measured using EDI-OCT before and 45 minutes after administration of the antiglaucomatous drops. RESULTS: SFCT revealed a significant increase in the left eye (administered antiglaucomatous drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.049) and a significant increase also in the right eye (administered artificial drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.001). However, SFCT did not reveal a significant increase in the left eye (p = 0.213) or in the right eye (p = 0.062) in the latanoprost group. CONCLUSION: Brinzolamide and betaxolol caused an increase in SFCT, while latanoprost had no significant effect on SFCT.

The protective effects of astaxanthin against cisplatin-induced retinal toxicity.

PURPOSE: This study investigated the toxic effects of an antineoplastic agent, cisplatin (CIS), on retinal cells and the potential capacity of astaxanthin (ASTA) to elicit a future therapeutic protocol in CIS-induced retinal toxicity. MATERIALS AND METHODS: Six groups were formed for the assessment; control (healthy; Group 1), olive oil (olive oil only; Group 2), ASTA control group (ASTA only, Group 3), the single intraperitoneal (IP) dose of 16 mg/kg CIS (CIS only group; Group 4), 16 mg/kg CIS +25 mg/kg (IP) ASTA (Group 5), and 16 mg/kg CIS +75 mg/kg (IP) ASTA (Group 6). On the third day after CIS administration, rats in all groups were sacrificed under anesthesia and the analysis of the biochemical parameters and histopathological levels were performed. RESULTS: A significant decrease in GSH levels and increases in MDA, eNOS, and 8-OHdG expressions were recorded. Additionally, CIS treatment had caused acidophilic staining in retinal histological appearance. ASTA treatment reduced the increases in MDA, eNOS, and 8-OHdG levels following CIS administration and increased the levels of GSH expressions, as well. CONCLUSIONS: These results may suggest that the ASTA molecule as a promising option to prevent retinal toxicity in patients receiving CIS treatment for malignant tumors.

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.

Measurement of Subfoveal Choroidal Thickness in Pseudoexfoliation Syndrome Using Enhanced Depth Imaging Optical Coherence Tomography.

BACKGROUND/AIM: Pseudoexfoliation (PSX) syndrome is associated with blood flow disturbances; however, its exact effect on choroidal blood flow and thickness remains to be elucidated. This study compared subfoveal choroidal thickness in normal eyes and in eyes with PSX using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: This prospective, cross-sectional study included 35 eyes of 35 patients (20 males, 15 females) with unilateral or bilateral PSX and 26 eyes of 26 healthy volunteers (13 males, 13 females). Besides a comprehensive ocular and physical examination, all subjects underwent EDI-OCT examination using an Optovue RTVue OCT device (Optovue Inc., Fremont, Calif., USA). RESULTS: The mean choroidal thickness (CT) and ocular perfusion pressure (OPP) were lower in the PSX group than in the healthy controls (249.4 ± 46.3 vs. 282.5 ± 55.8 µm, p = 0.014 and 40.7 ± 5.8 vs. 44.3 ± 4.3 mm Hg, p = 0.007, respectively). In addition, both systolic blood pressure and diastolic blood pressure measurements were lower among the PSX patients. However, no correlation was found between CT and OPP. CONCLUSION: The findings of this study suggest that PSX is associated with an overall thinning of the subfoveal choroid and a significant decrease in OPP. Future studies are warranted to further examine these relations.

Evaluation of Choroidal Thickness and Retinal Vessel Density with Serum HIF-1α and TNF-α Level in Patients with OSAS.

PURPOSE: To reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation. METHODS: This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay. RESULTS: The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7-2068) and 1027(453-2527), respectively], and were both significantly higher than the control group [(521.5(231.6-2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: -0.220 and p < 0.05, r: -0.252, respectively) and their DVD values (p < 0.001, r: -0.324 and p = 0.001, r: -0.299, respectively). CONCLUSIONS: Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients.

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.

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.

Glaucoma With Alkaptonuria as a Result of Pigment Accumulation.

PURPOSE: To report a case of alkaptonuria (AKU) in a patient with bilateral conjunctival and scleral black colorization who was diagnosed with glaucoma thereafter. METHODS: This is a single case report. RESULTS: A 67-year-old male patient with bilateral black colorization of conjunctiva and sclera was referred to our hospital. In the biomicroscopic examination, globular dark pigmentation was observed in the conjunctiva, sclera, and limbal cornea. The patient was diagnosed with a nuclear cataract in both eyes. He also had gray skin pigmentation at his nose and paranasal area. Corneal topography examination revealed irregular astigmatism. Intraocular pressure values were 29 and 31 mm Hg, in the right and left eye, respectively, with Goldmann applanation tonometry. The diagnosis of AKU was made after pathologic assessment of conjunctival biopsy by the internal medicine department. CONCLUSIONS: AKU is characterized by the accumulation of homogentisic acid in the connective tissues of many organs including the eye. Patients should be carefully examined in ophthalmology clinics in order to not miss systemic diagnoses. It should be kept in mind that AKU may cause iridocorneal angle pigmentation, which leads to glaucoma, and patients should be treated with proper medication when presenting with elevated intraocular pressure values.

Describing a New Mechanism of Retinal Detachment Secondary to Ophthalmic Artery Vasospasm Following Subarachnoid Hemorrhage: An Experimental Study.

BACKGROUND: The pterygopalatine ganglion (PPG) and ophthalmic arteries (OpAs) have important roles in ocular autoregulation and retinal and visual functions. The relationship between PPG neuron density, OpA vasospasm, and retinal detachment in subarachnoid hemorrhage (SAH) has never been studied. METHODS: This study was conducted on 25 rabbits. Five animals were in the control group (GI; n = 5), five in the sham group (GII; n = 5), and 15 in the study group (GIII; n = 15). After injection of 1 cc serum saline into the cisterna magna in the sham group, and autologous blood in the SAH group, the animals were followed for 3 weeks. All animals underwent a retinal examination five times a week for 3 weeks before and after the experiment. After the experiment, the neuron density of PPGs of the facial nerves, vasospasm index (VSI) of OpAs, and total basal surface values of the detached retinal parts (DRPs) were calculated. RESULTS: In the funduscopic examination, intravitreous hemorrhage ( Terson's syndrome) was detected in four animals in the SAH group. In the control groups, neuron density was 12,000 ± 1,240/mm3, VSI = 0.345 ± 0.076, and DRP = 0 to 1.5 mm2. Mean neuron density was 9,450 ± 940/mm3, VSI = 1.645 ± 0.940, and DRP = 6.23 ± 1.61 mm2 in the sham group (p < 0.05). Neuron density was 6,890 ± 932/mm3, VSI = 2.92 ± 0.97, and DRP = 9.43 ± 2.54 mm2 in SAH group. CONCLUSION: Mean neuron density, VSI of OpAs, and DRP values differed statistically significant between the SAH group and other groups (p < 0.005). There is an inverse relationship between PPG neurons and DRP. However, a direct relationship was observed between the mean VSI and DRP values.