An analysis of the relationship between ABCC8 and KCNJ11 gene polymorphisms and diabetic retinopathy in Turkish population.

BACKGROUND: Diabetic retinopathy (DR) occurs due to high blood glucose damage to the retina and leads to blindness if left untreated. KATP and related genes (KCNJ11 and ABCC8) play an important role in insulin secretion by glucose-stimulated pancreatic beta cells and the regulation of insulin secretion. KCNJ11 E23K (rs5219), ABCC8-3 C/T (rs1799854), Thr759Thr (rs1801261) and Arg1273Arg (rs1799859) are among the possible related single nucleotide polymorphisms (SNPs). The aim of this study is to find out how DR and these SNPs are associated with one another in the Turkish population. MATERIALS AND METHODS: This study included 176 patients with type 2 diabetes mellitus without retinopathy (T2DM-rp), 177 DR patients, and 204 controls. Genomic DNA was extracted from whole blood, and genotypes were determined by the PCR-RFLP method. RESULTS: In the present study, a significant difference was not found between all the groups in terms of Arg1273Arg polymorphism located in the ABCC8 gene. The T allele and the TT genotype in the -3 C/T polymorphism in this gene may have a protective effect in the development of DR (p = 0.036 for the TT genotype; p = 0.034 for T allele) and PDR (p = 0.042 and 0.025 for the TT genotype). The AA genotype showed a significant increase in the DR group compared to T2DM-rp in the KCNJ11 E23K polymorphism (p = 0.046). CONCLUSIONS: Consequently, the T allele and TT genotype in the -3 C/T polymorphism of the ABCC8 gene may have a protective marker on the development of DR and PDR, while the AA genotype in the E23K polymorphism of the KCNJ11 gene may be effective in the development of DR in the Turkish population.

Optical coherence tomography changes in ankylosing spondylitis patients on long-term adalimumab treatment.

OBJECTIVE: Long-term ocular effects of tumor necrosis factor-alpha inhibitors remain to be elucidated. This study aimed to examine the long-term effects of adalimumab use on neural tissue of the anterior visual pathways using optical coherence tomography in patients with ankylosing spondylitis. METHODS: This was a single-center, open-label, cross-sectional study conducted at the Giresun University Faculty of Medicine, Physical Medicine and Rehabilitation Department, between November 2019 and August 2020. This study included 26 ankylosing spondylitis patients receiving adalimumab for at least 1 year and 21 healthy controls. All subjects underwent a full ophthalmological examination and optical coherence tomography examination with the following measurements: peripapillary retinal nerve fiber layer thickness, peripapillary retinal thickness, peripapillary choroidal thickness, ganglion cell complex thickness, and the optic head properties. RESULTS: Peripapillary retinal nerve fiber layer thickness and retinal thickness measurements were lower in the adalimumab group. In addition, ganglion cell complex thickness was significantly lower and the cup-to-disc ratio was significantly higher in the adalimumab group (p<0.05). However, the two groups did not differ in terms of peripapillary choroidal thickness and disc area (p>0.05). CONCLUSION: Although tumor necrosis factor-alpha inhibitors have some favorable effects on the ocular involvement of patients with ankylosing spondylitis, they may also have paradoxical detrimental effects as evidenced by structural changes observed by optical coherence tomography. Future studies with better design, probably including a large number of patients with a range of rheumatological diseases and tumor necrosis factor-alpha inhibitors, are warranted.

Optical coherence tomography changes in ankylosing spondylitis patients on long-term adalimumab treatment

SUMMARY OBJECTIVE: Long-term ocular effects of tumor necrosis factor-alpha inhibitors remain to be elucidated. This study aimed to examine the long-term effects of adalimumab use on neural tissue of the anterior visual pathways using optical coherence tomography in patients with ankylosing spondylitis. METHODS: This was a single-center, open-label, cross-sectional study conducted at the Giresun University Faculty of Medicine, Physical Medicine and Rehabilitation Department, between November 2019 and August 2020. This study included 26 ankylosing spondylitis patients receiving adalimumab for at least 1 year and 21 healthy controls. All subjects underwent a full ophthalmological examination and optical coherence tomography examination with the following measurements: peripapillary retinal nerve fiber layer thickness, peripapillary retinal thickness, peripapillary choroidal thickness, ganglion cell complex thickness, and the optic head properties. RESULTS: Peripapillary retinal nerve fiber layer thickness and retinal thickness measurements were lower in the adalimumab group. In addition, ganglion cell complex thickness was significantly lower and the cup-to-disc ratio was significantly higher in the adalimumab group (p<0.05). However, the two groups did not differ in terms of peripapillary choroidal thickness and disc area (p>0.05). CONCLUSION: Although tumor necrosis factor-alpha inhibitors have some favorable effects on the ocular involvement of patients with ankylosing spondylitis, they may also have paradoxical detrimental effects as evidenced by structural changes observed by optical coherence tomography. Future studies with better design, probably including a large number of patients with a range of rheumatological diseases and tumor necrosis factor-alpha inhibitors, are warranted.

Evaluation of the effects of selective laser trabeculoplasty on anterior segment parameters by anterior segment optical coherence tomography.

To prospectively examine the effects of selective laser trabeculoplasty (SLT) on the anterior chamber angle (ACA) and its related parameters using anterior segment-optic coherence tomography (AS-OCT). Fifty eyes of 50 patients with primary open angle glaucoma (POAG) and ocular hypertension were included in the study. AS-OCT was performed before SLT application, immediately after and at 1 day and 1 month. Intraocular pressure (IOP), central corneal thickness (CCT) and anterior chamber depth (ACD) were also recorded and evaluated. No statistically significant difference was determined in ACA and other AS-OCT parameters (AOD, angle opening distance at 500 and 750 mm; TISA, trabecular-iris space area at 500 and 750 mm) before and 1 day after SLT application (p > 0.05). However, a statistically significant increase was determined in both the temporal and nasal ACA, AOD and TISA values between the baseline and day 30 (p < 0.001). No statistically significant change was observed in the CCT or ACD values (p > 0.05). SLT resulted in an increase in ACA, AOD and TISA when evaluated using AS-OCT. We think that this study provides a different perspective concerning the effects of SLT in the angle region and the involved mechanism.

The effects of intravitreal H2 S application on apoptosis in the retina and cornea in experimental glaucoma model.

One of the most important causes of visual loss (blindness) is glaucoma, which occurs due to the degeneration of the ganglion cells in retina. It has been shown that hydrogen sulphide (H2 S) acts an antioxidant, neuroprotective and neuromodulator and provides protection against oxidative stress and apoptosis. This study aims to examine through which apoptotic pathway H2 S acts in experimental glaucoma model. Twenty-two male wistar albino rats were used in this study. Group 1 (n = 6, control group): Intravitreal saline was given in the third week without inducing ocular hypertension (OHT) with laser photocoagulation. Group 2 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal saline was given in the third week. Group 3 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal H2 S's donor sodium hydrosulphide (NaSH) 100 nmol/L was given in the third week. At the end of the 6th week, the eyes of the rats were sacrified under anaesthesia and extracted and then routine tissue follow-up was undertaken. Besides haematoxylin & eosin (H&E) staining, Bax, Bcl-2, p53 and caspase-3 activation were examined immunohistochemically in the retina and the cornea. This showed that ocular hypertension caused apoptosis through the intrinsic pathway, due to Bax and caspase-3 activation, in both retina and cornea, and that this led to DNA damage due to p53 activation. Also, we found that H2 S exposure in glaucoma distinctly suppressed Bax, caspase-3 and p53 activations in retina but that it has a limited effect on the cornea. According to these results, glaucoma caused apoptosis in the retina through intrinsic pathway, and the damage to the retina could be compensated partially by H2 S but would have limited on the cornea.

Corneal thickness and endothelial changes in long-term hydroxychloroquine use.

Objective: To determine possible associations between long-term HCQ use and corneal changes in patients who used HCQ for at least 3 years. Materials and methods: The study included 62 healthy controls and 62 consecutive patients who used HCQ for the treatment of rheumatologic disease and were referred to the ophthalmology department between August 2018 and November 2018 for HCQ retinal toxicity screening. Central corneal thickness (CCT), corneal endothelial cell density (ECD), the coefficient of variation (CV) of cell size, and the percentage of hexagonal cells (HEX%) were measured to evaluate changes in the cornea. Results: The mean age of the patient group and control group was 50.10 ± 10.91 and 50.53 ± 10.67 years, respectively. The mean ECD was 2742 ± 347 (cells/mm2) in the patient group and 2875 ± 188 cells/mm2 in the control group. There was a significant difference between groups (p = 0.01). The mean CCT was 567.05 ± 32.35 µm in the patient group and 540.15 ± 38.50 µm in the control group. CCT was significantly higher in the patient group compared with control group (p < 0.001). There was no significant difference between groups in terms of mean CV and HEX values (p > 0.05). Conclusions: Patients using long-term HCQ demonstrated lower ECD and higher CCT than the control group. However, the CV of cell sizes and the HEX % values were not significantly different from the controls.

Evaluation of the optic nerve and scleral-choroidal-retinal layer with ultrasound elastography in glaucoma and physiological optic nerve head cupping.

AIM: To evaluate the strain ratio of the optic nerve and retina-choroid-sclera (RCS) layers in individuals with physiological optic disc cupping (PC) and glaucoma patients using strain elastography. MATERIAL AND METHODS: We evaluated 56 eyes of 56 subjects (20 eyes with glaucoma, 19 eyes with PC, and 17 normal eyes). The strain ratio of orbital fat to optic nerve (SROFON) was calculated as the ratio of the optic nerve to intraconal fat tissue and the strain ratio of orbital fat to retina-choroid-sclera (SROFRCS) was calculated as the ratio of RCS layers to intraconal fat tissue. RESULTS: SROFON was 0.92 in the control group, 1.07 in the PC group and 1.6 in the glaucoma group and a statistically significant difference was present between the three groups (p<0.05). SROFRCS had no statistically significant difference between the three groups. CONCLUSIONS:  SROFON values could contribute to the differentiation of the patients with glaucoma and PC.

The evaluation of retinal and choroidal structural changes by optical coherence tomography in patients with chronic obstructive pulmonary disease.

PURPOSE: To evaluate the retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCL+) thickness, and macular choroidal thickness (mCT) in patients with chronic obstructive pulmonary disease (COPD) using spectral domain optical coherence tomography (SD-OCT). METHODS: A total of 79 COPD patients and 71 age- and sex-matched healthy individuals were enrolled in this prospective cross-sectional study. The patients were divided into two subgroups (with mild-to-moderate COPD and severe COPD) using spirometric data suggested by the Global Initiative for Chronic Obstructive Lung Disease guideline. The RNFL, GCL+, and mCT were compared between groups. RESULTS: The average and nasal RNFL thicknesses in the COPD group were significantly lower than those in control group (p = 0.023 and 0.027 respectively). Statistically significant reductions in average thickness and in those of all six wedge-shaped GCL+ sectors were evident in the COPD group compared with control group and were more marked in patients with severe COPD. The other RNFL data did not differ significantly between COPD and control groups. The mCT was somewhat thinner at all the measured locations in COPD group compared with control group, but statistically significance was not attained. CONCLUSIONS: The study results revealed significant average, nasal RNFL, global GCL+ loss, and a nonsignificant choroidal thinning in patients with COPD compared to healthy subjects. The eye seems to be one of the affected tissues during the natural course of the COPD.

Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain.

PURPOSE: This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED). METHODS: Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively. RESULTS: The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p < 0.001 for each group). The mean vitamin B12 level at enrollment was 144.24 ±43.36 pg/ml in group 1 and 417.53 ±87.22 pg/ml in group 2. The mean vitamin B12 level in group 1 reached to 450 ±60.563 pg/ml after 12 weeks of treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2. CONCLUSIONS: These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular pain despite taking topical treatment.

Effects of Molsidomine on Retinopathy and Oxidative Stress Induced by Radiotheraphy in Rat Eyes.

PURPOSE: To determine the role of Molsidomine in preventing radiation-induced retinopathy after head and neck region irradiation of rats with a single radiation dose of 15 Gy. MATERIALS AND METHODS: Male Wistar albino rats were randomly grouped into five as follows: (1) control group rats, which were applied through an intraperitoneal (i.p.) vehicle without radiotherapy (RT); (2) RT group rats received a single dose of 15 Gy irradiation and after daily 0.1 ml vehicle i.p. for 5 consecutive days; (3) molsidomine (MOL) group rats were treated for 5 consecutive days by i.p. with 4 mg/kg/day MOL; (4) irradiation plus MOL group (RT+MOL) rats received irradiation and after 10 days single daily i.p. dose of MOL for 5 consecutive days; and (5) MOL+RT group rats were treated for 5 consecutive days by i.p. with MOL before RT. At the end of the work the rats were sacrificed under high-dose anesthesia on the 16th day and then eye tissues were taken for histopathological, immunohistochemical (caspase-3), and biochemical analyses (superoxide dismutase [SOD], glutathione peroxidase [GSH], and malondialdehyde [MDA]). RESULTS: RT significantly decreased both the content of GSH and the activity of SOD, and significantly increased the production of MDA level in the rat eyes. MOL treatment significantly increased the SOD and GSH levels and significantly decreased the MDA production (p < 0.0001). In addition, RT significantly increased the number of ganglion cells (GCs; p = 0.001), whereas especially pretreatment with MOL improved (p = 0.013). RT led to significant retinopathy formation, and MOL therapy protected the retina from radiation-induced retinopathy (p < 0.0001). CONCLUSIONS: We suggest that MOL is a powerful antioxidant and free radical scavenger that prevents the rat eyes from radiation-induced retinopathy and oxidative stress.

Histopathological and ophthalmoscopic evaluation of apocynin on experimental proliferative vitreoretinopathy in rabbit eyes.

The aim of the current study was to evaluate the effect of apocynin (APO) on the development of proliferative vitreoretinopathy (PVR). New Zealand-type male rabbits were randomly grouped into three as follows: (1) Sham group rabbits which were applied intraperitoneal (i.p.) vehicle without PVR; (2) PVR group rabbits where PVR was created and an i.p. vehicle was administered for 21 successive days; (3) PVR + APO group rabbits where PVR was created and i.p. APO was administered for 21 successive days. Fundus examination was conducted with an indirect ophthalmoscope before starting the experiments and at each visit afterwards. At the end of the work, the rabbits were sacrificed under high-dose anesthesia and then eye tissues were taken for histopathological analyses. In the PVR + APO group, histopathologic and ophthalmoscopic examination revealed significant decrease in PVR formation. As the result, it has been observed that APO at least partially inhibits PVR formation.

Effect of topical administration of tramadol on corneal wound healing in rats.

In this study, we aimed to investigate the effects of topical tramadol administration on corneal wound healing, and examine ophthalmic structures and intraocular pressure 7 days after tramadol administration. The experiments were conducted on eight male Wistar rats (250-300 g). After ophthalmic examination, epithelial cell layers in the central cornea were wounded. Rats received 30 µL of tramadol hydrochloride in one eye (Group Tramadol) and the same volume of vehicle in the other (Group Control) every 12 h for 7 days. Both eyes were stained with fluorescein dye, photographed, and wound area was calculated every 8 h until complete healing was observed. Eye blink frequency and corneal reflex tests were measured before and after drug administrations. After 7 days, slit lamp biomicroscopy, fundoscopy, Goldmann applanation tonometry, and histological evaluation were performed. There was no difference in the corneal wound healing rates between the tramadol and control groups. Reduction in wound area over time was also similar; group-time interaction was insignificant (F = 738.911; p = 0.225). Tramadol application resulted in blinking and blepharospasm for 30 s, but vehicle did not. Corneal reflex was intact and eye blink frequency test results were similar in all measurement times in both groups. Slit lamp biomicroscopy, fundoscopy, and intraocular pressures were within normal range. Corneal cells appeared unaffected by the repeated doses of tramadol for 7 days. Topical tramadol application on the cornea did not cause any side effect, except for initial temporary blinking and blepharospasm. Corneal wound healing was not affected, either.

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma.

AIM: To evaluate intraocular pressure (IOP)-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma. METHODS: Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale. RESULTS: Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2(nd) mo IOP measurements, and mean (%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels. CONCLUSION: Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.