Comparison of accelerated and conventional corneal collagen cross-linking for progressive keratoconus

Purpose: To compare outcomes of accelerated and conventional corneal cross-linking (CXL) for progressive keratoconus (KC).

Materials and methods: Patients were divided into two groups as the accelerated CXL group and the conventional CXL group. The uncorrected distant visual acuity (UDVA), corrected distant visual acuity (CDVA), refraction and keratometric values were measured preoperatively and postoperatively. The data of the two groups were compared statistically.

Results: The mean UDVA and CDVA were better at the six month postoperative when compared with preoperative values in two groups. While change in UDVA and CDVA was statistically significant in the accelerated CXL group (p?=?0.035 and p?=?0.047, respectively), it did not reach statistical significance in the conventional CXL group (p?=?0.184 and p?=?0.113, respectively). The decrease in the mean corneal power (K_m) and maximum keratometric value (K_max) were statistically significant in both groups (p?=?0.012 and 0.046, respectively in the accelerated CXL group, p?=?0.012 and 0.041, respectively, in the conventional CXL group). There was no statistically significant difference in visual and refractive results between the two groups (p?>?0.05).

Conclusions: Refractive and visual results of the accelerated CXL method and the conventional CXL method for the treatment of KC in short time period were similar. The accelerated CXL method faster and provide high throughput of the patients.     

Reduced central corneal thickness in patients with isotretinoin treatment

Context: It is well known that oral isotretinoin treatment causes numerous ocular side-effects.

Objective: To investigate the effect of systemic isotretinoin treatment on central corneal thickness (CCT) values due to meibomian gland disease (MGD).

Participants: In this prospective study, 47 patients (27 men, 20 women) with nodulocystic acne vulgaris treated with oral isotretinoin (0.8?mg/kg daily) were included.

Methods: All patients were analyzed with the Pentacam Scheimpflug topography at baseline, on the 3rd and 6th month of treatment. Main outcome measures were MGD scores and CCT.

Results: The mean age of patients was 25.1?±?4.4 years. The mean MGD scores were significantly higher at 3rd month (1.3?±?0.9) and 6th month (1.5?±?1.0) of treatment compared with baseline (1.1?±?0.9) (p?p?p?=?0.038, r?=??0.221).

Conclusion: Isotretinoin treatment causes higher MGD scores. A statistically significant decrease in CCT due to MGD was detected at 6th month of treatment.     

Effect of intravitreal injection of dexamethasone implant on corneal endothelium in macular edema due to retinal vein occlusion

Objective: To evaluate the effects of dexamethasone (DEX) implant (Ozurdex®) on corneal endothelium in patients with retinal vein occlusion complicated with macular edema.

Materials and methods: Patients (n?=?31) received 1–3 intravitreal DEX implants in one eye. Measurements were intraocular pressure (IOP) at baseline and 1, 3, and 6 months after the first intravitreal injection and corneal specular microscopy and central corneal thickness (CCT) at baseline and 1 and 6 months. We analyzed endothelial cell density (ECD), coefficient of variation of cell size (CV), and percentage of hexagonality.

Results: Mean follow-up period was 9.7?±?3.3 months. Mean number of injections was 1.5?±?0.8. Mean IOP values were 15.6?±?2.6?mm Hg at baseline, 17.7?±?3.6?mm Hg at one month, 16.4?±?4.1?mm Hg at three months, and 16.0?±?2.7?mm Hg at six months. There was a significant difference in mean IOPs at one month and six months (p?=?0.008). There were no significant differences in mean ECD (p?=?0.375), CV (p?=?0.661), percentage of hexagonality (p?=?0.287), and CCT (p?=?0.331).

Conclusion: Although intravitreal injection of 0.7?mg DEX causes moderate elevation of IOP, it does not seem to have detrimental effects on corneal endothelium at six months.     

Surgical rehabilitation following ocular chemical injury

Purpose: The purpose of this study is to evaluate the management of limbal stem cell deficiency (LSCD) secondary to chemical ocular burns.

Materials and methods: The charts of 48 eyes of 40 patients with grade 2 or higher chemical injury were evaluated retrospectively. Subjects with follow-up longer than 1 year were included. Medical treatment, surgical correction of abnormalities of ocular adnexial structures, limbal stem cell transplantation from patient’s fellow eye, from living relatives or from cadaveric donor, amniotic membrane transplantation, conjunctival epitheliectomy, chelation with ethylenediaminetetraacetic acid and penetrating keratoplasty were the treatment modalities. Outcome measures were ocular surface stability and corrected distance visual acuity (CDVA). Failure was defined as the appearance of persistent epithelial defect (nonhealing epithelial defect for more than 2 weeks) with progressive corneal conjunctivalization/vascularization and thinning, and also progression of conjunctivalization to the central 6?mm of the cornea in eyes with subsequent keratoplasty.

Results: The mean age of 31 male and 9 female patients were 32.32?±?12.6 years. LSCD was bilateral in 8 cases. The mean follow-up was 77.2?±?35.1 months. The presentations were in acute phase in 37.5%, in subacute phase in 32.5% and in chronic phase in 30% of the patients. Only 13 of 48 (27.1%) eyes obtained sufficient ocular surface stability through medical treatment; however, only 5 of these eyes achieved CDVA of less than 0.7 logMAR. Limbal stem cell transplantation was performed in 26 eyes as conjunctival limbal autograft, living-related conjunctival limbal allograft and keratolimbal allograft or as a combination of these transplantations. At the last visit, 30 eyes (62.5%) had an intact and stable ocular surface. Clear cornea was achieved in 11 (78.6%) of 14 eyes with grade 2 injury, in 9 (60%) of 15 eyes with grade 3 injury, in 5 (50%) of 10 eyes with grade 4 injury, in 1 (16.6%) of 6 eyes with grade 5 injury and in 1 (33.3%) of 3 eyes with grade 6 injury. The CDVA that was 1.66?±?0.99 logMAR initially improved to 0.87?±?0.85 logMAR at the last visit (p?Conclusion: While patients with low-grade chemical injury seem to benefit quite well from the medical treatment, amniotic membrane transplantation, limbal graft transplantation and subsequent keratoplasty; patients with severe injuries seem to be more prone to failure after all of the available treatment modalities.     

Effect of mydriasis induced by topical 0.5% tropicamide instillation on the corneal biomechanical properties in healthy individuals measured by ocular response analyzer

Purpose: This observational study aims to investigate the effects of tropicamide (0.5%) on corneal biomechanical properties, with the ocular response analyzer (ORA), in healthy individuals.

Methods: Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) measurements of 38 (21 female and 17 male) healthy individuals, before and after 30?min of 0.5% tropicamide instillation, were performed by using the ORA.

Results: The mean CH, CRF, IOPg and IOPcc measurements of the eyes were 10.2?±?1.9?mmHg, 10.3?±?2.1?mmHg, 15.7?±?3.4?mmHg, 16.4?±?3.3?mmHg pre-tropicamide, and 10.4?±?1.7?mmHg, 10.3?±?2.1?mmHg, 15.3?±?3.4?mmHg, 15.8?±?2.7?mmHg post-tropicamide, respectively. The differences between the pre- and post-tropicamide measurements of the eyes were insignificant (p?=?0.184, p?=?0.659, p?=?0.294, p?=?0.150, respectively; paired t-test).

Conclusions: A tropicamide instillation does not lead to significant changes in the corneal biomechanical properties. Therefore, it can be used safely in disease, i.e. in the diagnosis and follow-up ORA as it does not cause any change.     

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia

Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases.

Materials and Methods: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30?min, and after 10?min of ultraviolet A irradiation.

Results: Eleven eyes of eleven patients with progressive keratoconus (n?=?10) and iatrogenic corneal ectasia (n?=?1) were included in this study. The mean thinnest pachymetric measurements were 391.82?±?30.34?µm (320–434?µm) after de-epithelialization of the cornea, 435?±?21.17?µm (402–472?µm) following 30?min instillation of isotonic riboflavin solution without dextran and 431.73?±?20.64?µm (387–461?µm) following 10?min of ultraviolet A irradiation to the cornea.

Conclusion: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.     

Intravitreal bevacizumab and dexamethasone implant for treatment of chronic diabetic macular edema

Objective: To evaluate anatomical and functional outcomes of intraviteal bevacizumab (IVB) in patients with chronic diabetic macular edema (DME), and the effectivity and safety of dexamethasone implant in those unresponsive to regular IVB treatment. Methods: Thirty-five eyes of 35 patients (16 male and 19 female) with chronic DME (central foveal thickness (CFT) >?275?μm, duration >?6 months) received three injections of 2.5?mg IVB with six-week intervals. At 18 weeks, dexamethasone implant was applied to patients unresponsive to IVB. Main outcomes were the change in best corrected visual acuity (BCVA), CFT and ocular and systemic adverse effects for both drugs. The patients responsive to IVB were followed up for 36 weeks and those patients receiving dexamethasone implant were followed up for 24 weeks postoperatively. Results: At 18 weeks, the mean BCVA (0.68?±?0.40 logMAR, p?=?0.45) and CFT (453?±?169?μm, p?=?0.58) did not show any significant change compared to baseline (0.74?±?0.42 logMAR and 521?±?151?μm, respectively). In 20 patients (%57.1) responsive to IVB, the CFT was significantly improved from 12 to 36 weeks with the mean value of 295?±?42 μ (p?=?0.01). However, no significant difference was observed for BCVA during this period (p?=?0.17). Dexamethasone was implanted in 15 eyes (42.8%) unresponsive to IVB at 18 weeks. Statistically significant improvements were observed in BCVA (at postoperative 4 and 12 weeks) and CFT (at postoperative 4, 12 and 24 weeks). In addition, both parameters significantly worsened at 24 weeks compared to 12 weeks (p?<?0.001 and p?=?0.01, respectively). Conclusions: Patients with chronic DME should be followed in accordance with a fixed treatment protocol combining anti-VEGF and steroid treatments.     

The effects of smoking on corneal endothelial cells: a cross-sectional study on a population from Isfahan,Iran

Purpose: The aim of this study is to compare the effect of smoking in corneal endothelial cell number and morphology by specular microscopy on a non-smoker population.

Methods: Our cross-sectional study was performed on 150 participants from a non-smoker population. Non-contact specular microscopy (Tomey Corporation Inc., Nagoya, Japan) was performed in the center of the cornea of all subjects. The cell density (CD), average cell size (AVG), percent of hexagonality (HEX%) and central corneal thickness (CCT) were calculated and compared in both groups.

Results: Totally, 76 eyes of 76 smokers and 74 eyes of 74 non-smokers were enrolled in the study from 2015 to 2016. The mean age of smokers and non-smokers were 48.61?±?17.04 and 46.39?±?13.02, respectively. The mean number of pack/year among the smokers was 17.36?±?14.68. Also, the mean values of AVG and CD were significantly different for these two groups (p?=?0.011 and p?=?0.039, respectively). Other corneal endothelial variables did not show a significant difference between smokers and non-smokers (p?>?0.05). However, smokers with severe nicotine dependency had significantly greater AVG and lower CD in comparison with the non-smokers (p?=?0.004 and p?=?0.013, respectively).

Conclusion: Our study showed that smoking can cause significant changes in some of the corneal endothelial variables, but not all of them.     

Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine

Objective: To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.

Methods: A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.

Results: Mean age of the patients was 40.2?±?6.5?years. Mean CT at central fovea was 324?±?47?μm initially, 341?±?45?μm in the first month and 344?±?46?μm in the second month, thus first and second month measures were significantly higher than base values (p?p?=?0.001). Baseline ACD (3.66?±?0.22?mm) measures significantly decreased at the first month (3.63?±?0.22?mm) and second month (3.62?±?0.22?mm, p?=?0.009). Also, a significant reduction was detected in the first (36.2?±?4.9°) and second month (35.9?±?5.1°) ACA measures comparing with baseline (39.1?±?5.1°, p?=?0.05). A significant myopic shift was determined in the first and second month SphEq values (?0.08?±?0.6, ?0.10?±?0.6, respectively, p?=?0.05).

Conclusions: The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.     

Spectral domain-optical coherence tomographic findings in patients with ankylosing spondylitis under anti-tumor necrosis factor-alpha therapy

Objective: To evaluate the effect of tumor necrosis factor-alpha (TNF-α) blockade on the thickness of the peripapillary retinal nerve fiber layer (RNFL), the ganglion cell-inner plexiform layers (GCIPL), and the macula in ankylosing spondylitis (AS) patients under anti-TNF-α therapy.

Materials and methods: Twenty-one patients with AS received etanercept, or adalimumab, or infliximab for at least 6 months. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were measured before and 6 months after the beginning of the treatment. Peripapillary RNFL, four regional fields (superior, inferior, nasal, and temporal), GCIPL, and macular thicknesses of the patients were analyzed by optical coherence tomography before the treatment, at 3 months and 6 months after the beginning of the treatment.

Results: The mean BASDAI, ESR, and CRP values were 5.2?±?1.5, 31.6?±?21.7, and 15.7?±?13.9, respectively, at the beginning of the treatment and 2.3?±?1.7, 21.3?±?15.1, and 10.1?±?10.3, respectively, 6 months after the beginning of treatment. There were significant differences among the mean BASDAI, ESR, and CRP values at the beginning of treatment and 6 months later (p?p?=?0.007, and p?=?0.009, respectively). There were no significant differences among peripapillary RNFL (p?=?0.24), four regional fields (p?=?0.98, p?=?0.23, p?=?0.09, p?=?0.47), GCIPL (p?=?0.25), or macular (p?=?0.33) thicknesses of the patients during anti-TNF-α treatment. In addition, the mean intraocular pressure levels throughout the follow-up did not show significant variation on repeated-measures ANOVA (p?=?0.77).

Conclusions: TNF-α blockade does not seem to influence RNFL, GCIPL, or macular thickness of patients with AS in the short term.     

The short-term and long-term adverse ocular effects of fesoterodine fumarate

Aim: To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA).

Method: Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4?mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically.

Results: The mean age of 120 women was 52.06?±?9.39 years (30–70 years). The mean PD, IOP and AA values were 4.12?±?0.61?mm (3.00–5.70?mm), 15.58?±?1.74?mmHg (11–20?mmHg) 2.28?±?1.26?Diopter (D) (0.50–5.50?D) at baseline; 4.68?±?0.65?mm (3.20–5.80?mm), 16.11?± 1.72?mmHg (11–20?mmHg), 1.68?±?1.04?D (0.25–4.50?D) at 30th day; and 4.28?±?0.58?mm (3.10–5.70?mm), 16.09?±?1.96?mmHg (11–19?mmHg), 2.18?±?1.19?D (0.50–5.00?D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p?<?0.001 for each), the changes in IOP values were not as such (p?=?0.642). Visual complaint was not observed in any patient.

Discussion: The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient.     

Effect of oral photochemotherapy (8-methoxypsoralen + UVA) on the electrophysiologic function of retina

Context: Since we had observed electroretinographic (ERG) abnormalities in some patients undergoing photochemotherapy with normal eye examination, we decided to investigate the effects of this therapy on retinal function.

Objective: To investigate the effects of oral photochemotherapy (8-methoxypsoralen?+?Ultraviolet-A) on electrophysiologic function of retina.

Materials and methods: Patients with vitiligo, psoriasis or eczema were enrolled. Patients with any abnormal eye exam or a positive drug or family history for retinal disease were excluded. Baseline standard ERG was provided with the RETIport32 device. The second ERG was performed 6 months after the first and at least 1 week after the last photochemotherapy session (mean number of sessions: 45?±?11). The outcome measures were changes in rod response, standard combined response, single-flash cone response, 30-Hz flicker (N1-P1) and oscillatory potentials amplitudes.

Results: Forty patients were enrolled; 20 of them (mean age: 31.1?±?12 years) completed the study. The mean rod response b-wave amplitude decreased from 88.9?±?47.5 to 86.4?±?36.6 and standard combined response b-wave amplitude decreased from 266.52 to 261.85?µV (p?=?0.422 and p?=?0.968, respectively) and the standard combined response a-wave amplitude increased from 155.4?±?40.0 at baseline to 165.1?±?48.4 in the follow-up ERG (p?=?0.092). The mean single-flash cone response a-wave amplitude decreased insignificantly in the follow-up ERG trace (34.5?±?13.7 and 29?±?15.4, respectively, p?=?0.242). The mean single-flash cone response b-wave amplitude showed an insignificant increase (p?=?0.087). The amplitudes of 30-Hz flicker wave and oscillatory potentials did not change significantly in the follow-up ERG (p?=?0.551 and p?=?0.739, respectively).

Conclusion: Since no significant change in ERG traces was observed, oral photochemotherapy seems safe for retinal electrophysiologic function.     

Tiotropium bromide suppresses smoke inhalation and burn injury-induced ERK 1/2 and SMAD 2/3 signaling in sheep bronchial submucosal glands

The effects of tiotropium bromide on ERK 1/2, SMAD 2/3 and NFκB signaling in bronchial submucosal gland (SMG) cells of sheep after smoke inhalation and burn injury (S?+?B) were studied. We hypothesized that tiotropium would modify intracellular signaling processes within SMG cells after injury. Bronchial tissues were obtained from uninjured (sham, n?=?6), S?+?B injured sheep 48?h after injury (n?=?6), and injured sheep nebulized with tiotropium (n?=?6). The percentage (mean?±?SD) of cells showing nuclear localization of phosphorylated ERK 1/2, pSMAD 2/3, and NFκB (p65) was determined by immunohistochemistry. Nuclear pERK 1/2 staining was increased in injured animals as compared to sham, (66?±?20 versus 14?±?9), p?=?0.0022, as was nuclear pSMAD, 84?±?10 versus 20?±?10, p?=?0.0022. There was a significant decrease in pERK 1/2 labeling in the tiotropium group compared to the injured group (31?±?20 versus 66?±?20, p?=?0.013), and also a decrease in pSMAD labeling, 62?±?17 versus 84?±?10, p?=?0.04. A significant increase for NFκB (p65) was noted in injured animals as compared to sham (73?±?16 versus 7?±?6, p?=?0.0022). Tiotropium-treated animals showed decreased p65 labeling as compared to injured (35?±?17 versus 74?±?16, p?=?0.02). The decrease in nuclear expression of pERK, pSMAD and NFκB molecules in SMG cells with tiotropium treatment is suggestive that their activation after injury is mediated in part through muscarinic receptors.     

Effects of smoking on visual acuity of central serous chorioretinopathy patients

Background: The aim of this study was to evaluate the differences, in terms of visual outcome and treatment needs, between smokers and non-smokers central serous chorioretinopathy (CSCR) patients.

Methods: The files of 252 patients diagnosed with CSCR who had presented to the Retina Unit of the Ophthalmology Clinic at Dicle University Medical School in Turkey were retrospectively evaluated. Eighty-four smokers, with a known history of smoking of at least one pack-year, and 133 non-smokers were included, whereas 35 patients with additional pathologies were excluded from the study.

Results: Of the patients, 192 (88.5%) were male and 25 (11.5%) were female. The mean patient age was 38.8?±?8.1 years (range: 20–68 years). Visual acuity (VA) of the smoker and non-smoker groups was measured as 0.45?±?0.35 and 0.24?±?0.28 logarithm of the minimum angle of resolution (logMar), respectively, at the first visit; 0.19?±?0.29 and 0.06?±?0.14 logMar at the sixth month; and 0.07?±?0.14 and 0.02?±?0.05 logMar at the ninth month. VA measurements at presentation and during all examinations (1th, 6th and 9th month) were significantly different for the two groups. VA was lower in the smoker group. In 27 patients (12.4%), an additional treatment modality was needed. Of the 27 patients, only 8 (6%) were non-smokers, whereas 19 (22.6%) were smokers. There was no difference between groups in the recurrence rate during follow-up (p?=?0.907); 14 (16.7%) smokers and 8 (19.0%) non-smokers experienced a recurrence.

Conclusion: This study has shown that patients selected and who are current smokers have poorer vision and need longer treatment.     

Effects of exenatide versus sitagliptin on postprandial glucose,insulin and glucagon secretion,gastric emptying,and caloric intake: a randomized,cross-over study

ABSTRACT

Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients.

Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33?±?5?kg/m²; HbA_1c: 8.5?±?1.2%; 2-h PPG: 245?±?65?mg/dL. Patients received exenatide (5?µg BID for 1 week, then 10?µg BID for 1 week) or sitagliptin (100?mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581).

Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133?±?6?mg/dL versus 208?±?6?mg/dL, p?<?0.0001 (evaluable, N?=?61). Switching from exenatide to sitagliptin increased 2-h PPG by +73?±?11?mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by ?76?±?10?mg/dL. Postprandial glucose parameters (AUC, C_ave, C_max) were lower with exenatide than sitagliptin (p?<?0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (?15?±?4?mg/dL vs. ?19?±?4?mg/dL, p?=?0.3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50?±?0.26, p?=?0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88?±?0.03, p?=?0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90?±?0.04, p?=?0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56?±?0.05, p?<?0.0001). Exenatide reduced total caloric intake compared to sitagliptin (?134?±?97?kcal vs. +130?±?97?kcal, p?=?0.0227, N?=?25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature.

Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.     

The effect of voluntary fasting and dehydration on posterior ocular structures

Purpose: Islamic Ramadan is the month of fasting, in which intake of food and drink is restricted from sunrise until sunset. The objective of the present study was to find out the effects of religious fasting on posterior ocular structures.

Materials and methods: In this prospective study, 34 eyes of 34 healthy volunteers with a mean age of 34.09?±?7.20?years were enrolled. Volunteers with any systemic disorder and eyes with pathology or previous surgery were excluded. One week before Ramadan (non-fasting period) and during Ramadan (fasting period) at the same hours (at 08:00 and 16:00?h), choroidal, macular, and retinal nerve fibre layer (RNFL) thicknesses were measured by spectral domain optical coherence tomography. Results were compared using paired sample t-test, and a p value <0.05 was accepted as statistically significant.

Results: The comparison of 16:00-h measurements significantly revealed lower values during fasting period when compared non-fasting period for choroidal thickness (non-fasting and fasting, respectively; subfoveal: 299.26?±?41.3 and 280.03?±?38.75 p?p?p?=?0.001) and paracentral macular thickness (superior: p?=?0.002, inferior: p?=?0.010, temporal: p?=?0.013, and nasal: p?=?0.016). By contrast, no significant differences were found in the central macular thickness between the fasting and non-fasting periods (p?=?0.735). Also, no statistically significant difference was noted for RNFL thickness at the different periods and time points.

Conclusion: Our results reveal that Islamic religious fasting is associated with statistically significant alterations in choroidal and paracentral macular thickness in healthy volunteers. However, more detailed investigations should be designed to evaluate whether fasting has a pivotal influence on pathological conditions.     

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex

Purpose: The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL).

Materials and methods: Participants smoking for more than 10 years at least 1 pack of cigarettes a day and a control group, both including participants between ages of 20 and 50 years with no other systemic or ocular diseases were studied. After normality tests, an independent sample t test was used to analyze the differences in age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), GCIPL and RNFL values between the groups.

Results: There were 44 participants in each group. There were 32 (62.5%) men and 12(37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. Mean ages were 39.85?±?8.41 and 38.66?±?10.47 years, mean spherical equivalent (SE) values were ?0.15?±?0.4 and 0?±?0.29 dioptries in smokers and control groups, respectively. The IOP, AXL, GCIPL and RNFL values were 17.58?±?3.41?mmHg, 23.69?±?0.56?mm, 84.3?±?5.83?μm and 92.3?±?3.51?μm in the smokers group and 18.5?±?2.91?mmHg, 23.45?±?0.72?mm, 86.11?±?8.02?μm and 97.66?±?8.23?μm in the control group. The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18?±?26.14, 117.05?±?5.51, 64.95?±?8.67 and 63.5?±?6.88?μm in the smokers group and 130.81?±?11.8, 123.55?±?11.03, 72.44?±?9.84 and 58.44?±?7.48?μm in the control group. There were no significant difference of age, sex, SE, IOP, AXL and GCIPL values between the smokers and control groups (p?>?0.05). The mean RNFL was significantly thinner in the smokers group compared to controls (p?=?0.03, independent t test). Inferior and superior quadrants of RNFL decreased in smokers group (p?=?0.01 and p?=?0.03, respectively) but temporal and nasal quadrants did not seem to be changed (p?=?0.96 and p?=?0.07, respectively).

Discussion: Smoking may affect RNFL thickness but not GCIPL.     

Exenatide effects on diabetes,obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

ABSTRACT

Background: Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A_1c (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of?≥?3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety.

Methods: Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5?µg exenatide, or 10?µg exenatide for 30 weeks, followed by 5?µg exenatide BID for 4 weeks, then 10?µg exenatide BID for ≥3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas.

Results: 217 patients (64% male, age 58?±?10 years, weight 99?±?18?kg, BMI 34?±?5?kg/m², A1C 8.2?±?1.0% [mean?±?SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (?1.1?±?0.1% [mean?±?SEM]) were sustained to 3 years (?1.0?±?0.1%; p?<?0.0001), with 46% achieving A1C?≤?7%. Exenatide progressively reduced body weight from baseline (?5.3?±?0.4?kg at 3 years; p?<?0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n?=?116) had reduced ALT (?10.4?±?1.5?IU/L; p?<?0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (?6.1?±?0.6?kg vs. ?4.4?±?0.5?kg; p?=?0.03), however weight change was minimally correlated with baseline ALT (r?=??0.01) or ALT change (r?=?0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n?=?151). Triglycerides decreased 12% (p?=?0.0003), total cholesterol decreased 5% (p?=?0.0007), LDL-C decreased 6% (p?<?0.0001), and HDL-C increased 24% (p <?0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison.

Conclusion: Adjunctive exenatide treatment for ≥3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.     

Effect of chronic smoking on lens nucleus as assessed by Pentacam HR lens densitometry in young adults

Objective: To evaluate the effects of chronic tobacco smoking on lens nucleus by Pentacam HR lens densitometry (LD) in young adults.

Design: Prospective cross-sectional case series.

Methods: Thirty subjects (23?M, 7 F) who were chronic cigarette smokers (≥10 cigarettes/day for at least 2 years) (group 1) and another 30 subjects (23?M, 7 F) who did not smoke (group 2), were included in this study. The patients were matched for age and sex between the groups. The exclusion criteria were any history of ocular surgery, any systemic disorders and any ocular diseases except for mild refractive disorders. Lens densitometry measurements were done with the Pentacam HR (Oculus, Wetzlar, Germany). The Schirmer test and pachymetry measurements were also performed.

Results: Mean age of the patients for both groups was 28.90?±?8.20 years (range: 18–40 years). Mean lens densitometry (LD) measurements of Group 1 (chronic cigarette smoking group) were higher than those of Group 2 (control group) in all LD techniques; however only mean “peak” LD measurements showed a statistically significant difference between these two groups (Group 1: 8.67?±?0.61, Group 2: 8.44?±?0.70, p?=?0.04). The mean Schirmer test value was 12.43?±?5.60?mm in Group 1 and 13.00?±?4.26?mm in Group 2 (p?=?0.55). The mean central corneal thickness (CCT) value was 564.23?±?34.61?µm in Group 1 and 550.47?±?32.94?µm in Group 2 (p?=?0.03).

Discussion: The Pentacam HR LD seems to be an important option for the evaluation of lens nucleus in young adults, because it gives objective and quantitative data.

Conclusion: Although chronic smoking increases lens nucleus density in young adults, the effect is not statistically significant when compared with the control group.     

Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats

Abstract

Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemia-reperfusion-induced injury in rats.

Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl₄ in rats.

Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl₄ at a dose of 2?ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80 MU/kg) or hepatocyte growth-promoting factor (pHGF; 100?mg/kg) daily for the next 4 weeks.

Results: rBPTI significantly prevented the disruption of liver function of alanine aminotransferase (ALT; 172.7?±?18.16 versus 141.2?±?15.28, p?=?0.003), aspartate aminotransferase (AST; 225.10?±?36.54 versus 170.06?±?27.14, p?=?0.007) and hydroxyproline (Hyp; 1.14?±?0.27 versus 0.62?±?0.17, p?=?0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15?±?0.16 versus 0.87?±?0.15, p?=?0.003) and increased the activities of superoxide dismutase (SOD; 6.07?±?0.95 versus 7.75?±?1.12, p?=?0.007). rBPTI reduced the production of cytokines of IL-1β and TGF-β. The hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell infiltration were ameliorated by rBPTI administration.

Conclusion: This study demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver fibrosis induced by CCl₄, which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.