The effect of topical ketorolac tromethamine on macular thickening after phacoemulsification in diabetic patients.

BACKGROUND: To determine the effect of ketorolac tromethamine 0.5% in preventing post-phacoemulsification macular thickening. This randomized clinical trial. patients randomized 1:1 to receive either topical ketorolac three times a day or a placebo. METHODS: A total of 101 eyes of 101 diabetic patients who were scheduled for phacoemulsification and had normal macular contour and thickness enrolled consecutively. The topical ketorolac and placebo were prescribed on the day before surgery and continued up to 4 weeks after surgery. Patients with proliferative diabetic retinopathy, a history of intravitreal injection in less than three months, a history of macular photocoagulation in less than 6 months, and any other concomitant ocular pathologies were excluded. Central macular thickness (CMT) and best corrected visual acuity (BCVA) was recorded in the follow-ups of 6, 12, and 24 weeks after the surgery and compared with the controls. RESULTS: 49 eyes in the case group and 52 eyes in the control group were analyzed. Mean BCVA was significantly improved in both groups at all follow-ups (P < 0.001 for all). There was no statistically significant difference regarding the BCVA in different time points except week 12 (P = 0.028) among the study group. In the case and control groups, CMT was increased at all follow-ups (P < 0.05). There was no statistically significant difference when comparing the two groups regarding the mean of CMT at any time point postoperatively (P > 0.05 for all). CONCLUSION: Based on our findings, topical ketorolac tromethamine 0.5% is not effective in the prevention of post-phacoemulsification macular thickening in diabetic patients. TRAIL REGISTRATION: The study protocol was registered into www. CLINICALTRIAL: gov with the RCT registration number NCT03551808. (2018/06/11 ) CLINICAL TRIAL REGISTRATION NUMBER: NCT03551808.

The Dynamics of Viruslike Capsid Assembly and Disassembly.

Cowpea chlorotic mottle virus (CCMV) is a widely used model for virus replication studies. A major challenge lies in distinguishing between the roles of the interaction between coat proteins and that between the coat proteins and the viral RNA in assembly and disassembly processes. Here, we report on the spontaneous and reversible size conversion of the empty capsids of a CCMV capsid protein functionalized with a hydrophobic elastin-like polypeptide which occurs following a pH jump. We monitor the concentrations of T = 3 and T = 1 capsids as a function of time and show that the time evolution of the conversion from one T number to another is not symmetric: The conversion from T = 1 to T = 3 is a factor of 10 slower than that of T = 3 to T = 1. We explain our experimental findings using a simple model based on classical nucleation theory applied to virus capsids, in which we account for the change in the free protein concentration, as the different types of shells assemble and disassemble by shedding or absorbing single protein subunits. As far as we are aware, this is the first study confirming that both the assembly and disassembly of viruslike shells can be explained through classical nucleation theory, reproducing quantitatively results from time-resolved experiments.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS OF RETINAL HYPERPERMEABILITY AND CHOROIDAL INFLAMMATION AS PREDICTORS OF SHORT-TERM FUNCTIONAL AND ANATOMICAL OUTCOMES IN EYES WITH DIABETIC MACULAR EDEMA TREATED WITH INTRAVITREAL BEVACIZUMAB.

PURPOSE: To assess spectral domain optical coherence tomography biomarkers of short-term outcomes in eyes with diabetic macular edema treated with intravitreal bevacizumab. METHODS: In a prospective interventional case series, 66 eyes with diabetic macular edema underwent 3 monthly intravitreal bevacizumab injections. Best-corrected visual acuity measurement and spectral domain optical coherence tomography were performed at baseline and at 3 months. Multivariate regression analysis was performed to investigate the baseline spectral domain optical coherence tomography parameters as predictors of functional and anatomical outcomes. RESULTS: Patients with diabetic nephropathy had greater subfoveal choroidal thickness (300.8 ± 35.54 vs. 253.0 ± 50.07 µm, P < 0.01) and were more likely to have subretinal fluid (r = 0.26, P = 0.03) at baseline. Multivariate analysis showed that the extent of external limiting membrane disruption (P = 0.03) and the extent of disorganization of retinal inner layers (P = 0.03) at baseline were predictors of best-corrected visual acuity at 3 months, whereas the extent of disorganization of retinal inner layers (P = 0.04) and duration of diabetes mellitus (P = 0.03) were predictors of central subfield thickness at 3 months. CONCLUSION: External limiting membrane disruption and disorganization of retinal inner layers, as the spectral domain optical coherence tomography biomarkers of retinal hyperpermeability, can predict short-term outcomes in diabetic macular edema eyes treated with intravitreal bevacizumab.

PANRETINAL PHOTOCOAGULATION VERSUS INTRAVITREAL BEVACIZUMAB VERSUS A PROPOSED MODIFIED COMBINATION THERAPY FOR TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Three-Arm Clinical Trial (CTPDR Study).

PURPOSE: To compare safety and therapeutic effect of three treatment protocols on patients with naive proliferative diabetic retinopathy. METHODS: A total of 207 eyes with proliferative diabetic retinopathy were randomly divided into three groups: full panretinal photocoagulation group; intravitreal bevacizumab (IVB) group with four monthly IVB injections; and modified combination group with two bimonthly IVB injections and a modified laser therapy. The best-corrected visual acuity and area of neovascularization leakage were compared at 1-year follow-up. RESULTS: The difference in final best-corrected visual acuity was not significant between the groups (P = 0.77). The modified combination group had the lowest final leakage area (P = 0.006). The difference in final mean deviation of visual field was not significant between IVB and modified combination groups (mean difference = 0.25, P = 0.23, 95% confidence interval, 0.12-1.38). There was no difference in rate of new-onset diabetic macular edema between IVB and modified combination groups (mean difference = 1.5%, P = 0.31, 95% confidence interval, 1.1-1.88). Mean of total IVB injections were 3.5, 7.4, and 6.2 for panretinal photocoagulation, IVB, and modified combination groups, respectively (P = 0.002). Patients in the IVB group underwent more visits (P = 0.001). In subgroup analysis, the difference in the final leakage area was significant for the eyes with diabetic macular edema (P = 0.005). CONCLUSION: A combination protocol of photocoagulation and IVB can be recommended for proliferative diabetic retinopathy, especially with baseline diabetic macular edema.

Topical ketorolac as an adjunctive treatment with intravitreal bevacizumab in the management of diabetic macular edema: A double-masked placebo-controlled randomized clinical trial.

PURPOSE: To evaluate the additional effect of ketorolac eye drops on therapeutic effects of intravitreal Bevacizumab in patients with diabetic macular edema (DME) METHODS: In a randomized clinical trial, 50 patients with center involved DME (macular thickness ≥ 300 microns accompanied by decreased VA (24 < BCVA ≤ 70 ETDRS letters) were enrolled consecutively and randomized 1:1 to receive either bevacizumab plus topical ketorolac (25 patients) or bevacizumab plus artificial tears (25 patients). Patients with proliferative diabetic retinopathy, history of intraocular surgery, intravitreal injection in less than three months, macular photocoagulation less than 6 months and any other concomitant ocular pathologies were excluded from the study. All the patients received three consecutive monthly injections of intravitreal bevacizumab (IVB). After that, patients were examined every 6 weeks and reinjection was administered based on the "as needed" protocol if macular thickness was 300 microns or more and VA was 70 ETDRS letters or less.. Patients also received either topical ketorolac or artificial tears three times a day over the study period (6 months). Changes in central subfield thickness (CST), best-corrected visual acuity (BCVA, ETDRS letters), and number of IVB injections were compared between the study groups. RESULTS: Fifty eyes of 50 patients were included (25 eyes in each group). Mean CST was significantly decreased in both study groups at 14th week (-87 ± 98 µm, P = 0.012 and -100 ± 147 µm, P = 0.006 in bevacizumab plus ketorolac and bevacizumab plus artificial tears groups, respectively). Nevertheless, the changes of mean CST remained significant only in bevacizumab plus ketorolac group up to 26th week (-147 ± 124 µm, P < 0.001 and -51 ± 145 µm, P = 0.245, respectively). Comparing two groups, reduction of mean CST from baseline was significantly greater in bevacizumab plus ketorolac group compared with the control group at 26th week. (difference = -97 µm, 95%CI = -182 to -11, P = 0.017). In the study group, mean BCVA significantly increased at both 20th week (6.2 ± 10.1, P = 0.04) and 26th week (8.2 ± 10.9, P = 0.03). In contrast, visual acuity did not significantly improve at any time points in bevacizumab plus artificial tears group, While insignificant, the 26-week mean change of visual acuity from baseline was greater in bevacizumab plus ketorolac group (difference = 6.5 ETDRS letter; 95%CI = -14.4 to 1.4) Two groups were comparable regarding number of IVB injections (P = 0.99). CONCLUSION: Topical ketorolac 0.5% three times a day could enhance and sustain the efficacy of intravitreal bevacizumab in the treatment of DME.

A novel method for electroretinogram assessment in patients with central retinal vein occlusion.

PURPOSE: Central retinal vein occlusion (CRVO) is the second most common retinal vascular disorder after diabetic retinopathy that affects the eyes. We propose a method for distinction of normal and central CRVO eyes based on electroretinogram (ERG). METHODS: Seventeen patients with CRVO in one eye were analyzed. Their ERG signals were collected in six different stimuli, including four records in the darkness (dark-adapted 0.01, dark-adapted 3.0, dark-adapted oscillatory potentials, and dark-adapted 10) and two records in brightness (light-adapted 3.0 and light-adapted 30 Hz flicker). Nonlinear features such as Hurst exponent (HE) and approximate entropy (ApEn) were extracted from healthy and CRVO eyes. Finally, a parabolic mapping and two criteria (theta angle and the density of points) were proposed to distinguish the groups. RESULTS: For ApEn, the P values of dark-adapted 3.0 oscillatory (P = 0.0433) and flicker (P = 0.0425) confirmed significant differences between the groups. For HE, the P values of dark-adapted 3.0 oscillatory (P = 0.0421) and flicker 30 Hz (P = 0.0402) confirmed differences between the healthy and CRVO groups. The P values of theta angle for dark-adapted 3.0 (P = 0.0199), dark-adapted oscillatory (P = 0.0265), dark-adapted 10.0 (P = 0.0166), light-adapted 3.0 (P = 0.0411), and flicker (P = 0.0361) showed significant differences. Using the density criterion, the statistical test demonstrated a significant difference between the groups in dark-adapted 3 (P = 0.0038), dark-adapted oscillatory (P = 0.0102), dark-adapted 10.0 (P = 0.0071), light-adapted 3.0 (P = 0.0319), and flicker 30 Hz (P = 0.0076). CONCLUSION: The proposed features have made it possible to distinguish between healthy and CRVO eyes. This method could be helpful in some cases with no definite diagnosis or to estimate the severity of CRVO.

PERIPHERAL ISCHEMIC RETINAL PHOTOCOAGULATION IN ADDITION TO INTRAVITREAL BEVACIZUMAB VERSUS INTRAVITREAL BEVACIZUMAB ALONE FOR THE TREATMENT OF MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION: A Randomized Double-Masked Controlled Clinical Trial.

PURPOSE: To investigate the effects of peripheral ischemic retinal photocoagulation in addition to intravitreal bevacizumab (IVB) in the treatment of macular edema due to ischemic central retinal vein occlusion. METHODS: Forty-eight eyes of 48 treatment-naive patients were randomly selected and divided into 2 groups. Group A comprised 24 eyes that were treated with three consecutive monthly injections of IVB, and Group B comprised 24 eyes that were treated with IVB plus photocoagulation of the peripheral nonperfused retina. Further IVB injections were administered as needed in both groups. Monthly follow-up was conducted for 9 months after the first injection. RESULTS: The data of 46 patients were analyzed. Best-corrected visual acuity changes from the fourth to eighth month follow-up in comparison with the baseline were significantly higher in Group B (P = 0.002-0.044-0.002-0.002-0.012). In addition, significant differences were observed in central macular thickness in Group B throughout the study period (all P < 0.001). Group B required less frequent IVB injections during the 9-month study period. CONCLUSION: Photocoagulation of the retinal nonperfused area in patients with macular edema because of central retinal vein occlusion might amplify the beneficial effects of IVB on best-corrected visual acuity and central macular thickness and reduce the frequency of IVB injection.

Combination of intravitreal bevacizumab and erythropoietin versus intravitreal bevacizumab alone for refractory diabetic macular edema: a randomized double-blind clinical trial.

PURPOSE: To evaluate the effect of three intravitreal bevacizumab (IVB) injections alone or in combination with intravitreal erythropoietin (EPO) in the treatment of refractory diabetic macular edema (DME). METHODS: In a randomized double-blind clinical trial, 48 eyes of 34 diabetic patients with refractory DME were enrolled. Eyes were randomly assigned to receive either 3 monthly injections of 0.05 cc (1.25 mg) IVB plus 0.05 cc (1000 unit) EPO or 0.05 cc (1.25 mg) IVB alone. Main outcome was best-corrected visual acuity (BCVA) changes and secondary outcome was central macular thickness (CMT). The patients were followed for 6 months. RESULTS: Mean BCVA changes up to 4 and 6 months were insignificant in both groups. It changed from 0.72 ± 0.56 logMAR at baseline to 0.74 ± 0.5 (P = 0.85) and 0.71 ± 0.44 (P = 0.40) in the combination group and from 0.48 ± 0.39 logMAR to 0.47 ± 0.35 (P = 0.48) and 0.52 ± 0.33 (P = 0.69) in the IVB alone group, at 4 and 6 months, respectively. The difference of mean BCVA changes between the groups was insignificant at both 4 and 6 months (P = 0.07 and P = 0.36, respectively). Within the group changes of mean CMT were significant only in the combination group at 4 and 6 months, from 518 ± 134 µ at baseline to 472 ± 151 to 475 ± 167 µ, respectively (P = 0.01 and P = 0.05). Corresponding changes were not significant in the IVB alone group. However, the difference between the groups was not significant at all visits (P = 0.51 and P = 0.71, respectively). CONCLUSIONS: This clinical trial demonstrated that intravitreal erythropoietin had no additional effect to IVB in the treatment of refractory DME in the short term. TRIAL REGISTRATION: Clinical trials.gov identifier: NCT03821168.

Peripapillary retinal nerve fiber layer thickness in preeclampsia and eclampsia.

PURPOSE: To evaluate peripapillary retinal nerve fiber layer (RNFL) thickness during and after pregnancy in pregnant women with preeclampsia or eclampsia and compare it with normotensive pregnant women as controls. METHODS: In a prospective comparative case-control study 35 women (70 eyes) with mild to moderate preeclampsia, 70 women (140 eyes) with severe preeclampsia and eclampsia, and 44 (88 eyes) healthy pregnant women were enrolled in three groups. Peripapillary RNFL thickness in three groups was measured after 28 weeks of pregnancy and 2 months postpartum by using optical coherence tomography. Mean and quadratic RNFL thickness changes were compared within and among the groups. RESULTS: Mean peripapillary RNFL thickness decreased significantly from 104 ± 10, 104 ± 23, and 106 ± 9 µm during pregnancy to 101 ± 10, 96 ± 10, and 103 ± 9 µm 2 months after pregnancy in the mild to moderate preeclampsia, severe preeclampsia and eclampsia, and healthy pregnant women groups, respectively (P < 0.001 for all). While the difference among the groups was insignificant during pregnancy, it reached to a significant level after delivery (P = 0.006). The highest reduction in mean RNFL thickness (6 ± 10 µm) occurred in the severe preeclampsia and eclampsia groups. CONCLUSIONS: In relation to the time of pregnancy, peripapillary RNFL reduced in preeclamptic and eclamptic cases as well as in normotensive pregnant women at 2 months postpartum. This reduction was more in the severe forms of pregnancy-induced hypertension.

Extended targeted retinal photocoagulation versus conventional pan-retinal photocoagulation for proliferative diabetic retinopathy in a randomized clinical trial.

PURPOSE: To determine the clinical efficacy of extended targeted retinal photocoagulation (ETRP) compared to conventional panretinal photocoagulation (CPRP) in proliferative diabetic retinopathy (PDR). METHODS: In a single-masked randomized clinical trial, 270 eyes of 234 patients with naïve early or high-risk PDR were randomly assigned to receive either CPRP or ETRP (135 eyes, each treatment arm). Best-corrected visual acuity (BCVA) measurement, fundus examination, wide-field fluorescein angiography (WFFA) and optical coherence tomography were carried out before and 3 months after retinal photocoagulation. Primary outcome was early PDR regression, specified as reduction in retinal neovascularization based on WFFA at 3 months. Secondary outcomes were BCVA and central macular thickness (CMT) changes. RESULTS: There were significantly more high-risk PDR eyes in ETRP group compared to CPRP (109 and 94 eyes, respectively, P = 0.04). Early PDR regression occurred in 71.9 and 64.4% of eyes in the ETRP and CPRP groups, respectively (P = 0.19). The mean number of applied laser spots in the ETRP was significantly fewer than CPRP (1202 vs. 1360, respectively, P < 0.001). Mean BCVA at baseline and 3 months post-laser were 0.37 ± 0.26 and 0.47 ± 0.19 logMAR in the ETRP arm, respectively. In the CPRP arm these values were 0.40 ± 0.27 and 0.47 ± 0.24 logMAR, respectively. Although mean BCVA decreased significantly in both treatment arms (ETRP P < 0.001, CPRP P = 0.009), the difference was not significant between arms (P = 0.68). CMT increased significantly in both groups (ETRP 41.08 µm, P < 0.001, CPRP 33.31 µm, P < 0.001). Nevertheless, the difference between the groups was not significant (P = 0.26). CONCLUSIONS: ETRP with fewer number of laser spots may be an appropriate alternative to CPRP in PDR regression at least through 3 months. GOV REGISTRATION NUMBER: NCT01232179.

The effect of topical sodium diclofenac on macular thickness in diabetic eyes after phacoemulsification: a randomized controlled trial.

To evaluate the efficacy of prophylactic administration of the topical diclofenac 0.1 % on macular thickness in diabetic patients following phacoemulsification and intraocular lens implantation surgery. In a Randomized double-masked clinical trial, 108 eyes of 108 diabetic patients underwent phacoemulsification and intraocular lens implantation surgery were enrolled. Fifty four eyes received the conventional postoperative care with steroid drop, whereas the other group (54 eyes) was given a preoperative diclofenac drop four times daily in addition to steroid drop and continued 6 weeks after surgery. All patients were evaluated by optical coherence tomography (OCT) preoperatively and days 1, 30, and 90. The outcome measures including best-corrected visual acuity and OCT findings were compared in and between both groups. Mean CMT changed from 239 ± 16 and 235 ± 17 at baseline to 249 ± 15 and 254 ± 28 at 3 months in the case and control groups, respectively(p = 0.003). Mean total volume of macula changed from 7.61 ± 0.22 and 7.56 ± 0.3 at baseline to 7.64 ± 0.22 and 7.65 ± 0.31 at 3 months in the case and control groups, respectively (p = 0.820). In comparison to the quadrants thicknesses and mean of them between groups did not reach the significant level. This study showed that there is a beneficial effect of topical diclofenac for prevention of macular thickness increasing following phacoemulsification in diabetic patients.

C-reactive protein and complement factor H polymorphism interaction in advanced exudative age-related macular degeneration.

PURPOSE: To determine the association of C-reactive protein (CRP) and complement factor H (CFH) gene with exudative age-related macular degeneration (AMD) and any possible interaction among these factors. METHODS: In this case-control study, 139 unrelated patients with exudative AMD and 123 non-AMD controls were recruited. Blood sample was taken for analysis of the CRP levels and DNA testing. DNA fragments of CFH gene variants containing 4 single nucleotide polymorphisms including rs800292, rs1061170, rs2274700, and rs3753395 were assessed. A CRP level of ≥3 mg/L was considered as elevated. The association of elevated CRP and CFH gene variants polymorphism with exudative AMD was compared between the groups. RESULTS: Mean age was 72.6 ± 6.4 for controls and 74.9 ± 7.4 for case group (P = 0.006). The difference between CRP levels in cases and controls was not statistically significant (P = 0.055). However, Y402H variant of CFH in both homozygous and heterozygous carriers C allele was significantly more frequent among exudative AMD patients than controls, 32.1 versus 6.5 % (P < 0.001). Evaluating various CRP levels in patients with CC and non-CC genotypes disclosed that in CC genotype group, higher CRP level (>3 mg/L) was associated with higher risk of developing exudative AMD (OR = 12.0, CI: 1.5-98.8) compared with the control group. CONCLUSION: This study disclosed no difference in CRP levels per se between exudative AMD patients with control group. However, higher levels of CRP in the presence of C allele of Y402H might confer more risk for the development of exudative AMD.

Comparison of four surgical techniques for management of pseudophakic and aphakic retinal detachment: a multicenter clinical trial.

PURPOSE: To compare the visual and anatomical outcomes of four surgical techniques to manage pseudophakic and aphakic retinal detachment (PARD). METHODS: In a multicenter randomized clinical trial, 211 eyes of 211 patients with PARD and proliferative vitreoretinopathy (PVR) grade B or less were randomly assigned to one of the four treatment groups: (1) scleral buckling (SB), 50 eyes, (2) vitrectomy without band, 51 eyes, (3) vitrectomy with encircling band (EB), 58 eyes, and (4) triamcinolone acetonide (TA) assisted vitrectomy, 52 eyes. Patients were followed for 12 months after the surgery. The best-corrected visual acuity (BCVA) and retinal reattachment rate at each follow-up time point were considered as the primary outcome measures. PVR, macular pucker, and cystoid macular edema were considered as the secondary outcomes. RESULTS: Visual improvement was achieved in all treatment groups relative to the baseline at all time points (all Ps < 0.001). There were no statistically significant differences among the groups with regard to BCVA changes. However, there was a significant difference in the slope of visual improvement curve: the SB group had a more rapid visual improvement compared to the vitrectomy with buckle group at month 12 (P = 0.032). The retinal reattachment rates at month 12 were 75, 64.7, 68.5, and 66.7 % in SB, vitrectomy without buckle, vitrectomy with EB, and TA-assisted vitrectomy groups respectively (P > 0.99). There were no statistically significant differences among the groups in terms of adverse events. CONCLUSIONS: SB, TA-assisted vitrectomy, and vitrectomy with and without buckle had comparable outcomes in the management of PARD.

Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular ischemia: a randomized controlled trial.

The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect.

Uveitis profile and treatment response in Iranian patients with sarcoidosis.

The aim of the study was to assess the clinical features and treatment responses in Iranian patients with sarcoid uveitis. A retrospective review of patients diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral clinic in Tehran, Iran. Demographic and clinical features of patients, treatment modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean duration of follow-up was 44.7 ± 45 months (range 3-175). Thirty-six eyes (54.5 %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of uveitis. All of the patients finally responded to treatment in the form of inflammation reduction and/or vision improvement. The average time interval before initial clinical response following treatment was 3.2 ± 3 months (range 1-72). This study disclosed a higher predominance of females and intermediate form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory drugs combined with corticosteroids resulted in good visual outcome and control of uveitis with a possible fewer corticosteroid side effects.

Intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial.

The purpose of the study is to compare single injection of intravitreal diclofenac (IVD) with intravitreal bevacizumab (IVB) in the treatment of eyes with naïve diabetic macular edema (DME). In this randomized clinical trial, 57 eyes of 57 patients were randomly assigned to IVD group (30 eyes), cases who received a single intravitreal injection of diclofenac (500 µg/0.1 ml), and IVB group (27 eyes), cases who received a single intravitreal injection of bevacizumab (1.25 mg). Change in best-corrected visual acuity in logMAR at week 12 was the primary outcome measure. Secondary outcomes included changes in central macular thickness, macular leakage, and potential injection-related complications. Best-corrected visual acuity improved significantly more in the IVD group than in the IVB group (P = 0.033), from 0.57 ± 0.25 to 0.49 ± 0.31 versus 0.55 ± 0.24-0.59 ± 0.27 logMAR at 12 weeks, respectively. However, the difference of macular thickness changes was in favor of IVB, but not to a significant level. The amount of change in leakage was not significantly different between the groups either. None of the eyes, in either group, developed ocular hypertension (≥23 mmHg) or cataract progression. No important injection-related complication was observed during the study period. This study demonstrated the superiority of IVD over IVB in the treatment of naïve DME regarding functional, but not anatomical outcomes. Therefore, using IVD as an adjunct or even alternative to other treatments might enhance the functional outcomes in such cases. Further studies are warranted to confirm potential benefit of IVD observed in this study.

COMPARISON OF PRE-EMPTIVE EFFECT OF MELOXICAM AND CELECOXCIB ON POST-OPERATIVE ANALGESIA: A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL.

INTRODUCTION: Pre-emptive analgesia may reduce pain, accelerate recovery and shorten the duration of hospitalization. The present study aims to compare the preemptive analgesic effects of meloxicam and celecoxib in patients undergoing lower limb surgery. METHOD: In this double blind randomized clinical trial, 70 patients, undergoing lower extremity surgery, entered in the study; thirty five patients were randomly allocated to either group using random allocation software. Meloxicam (15 mg) was administered orally to one group two hours before the surgical onset. The other group was treated with oral celecoxib (400 mg) two hours before the operation. Pain severity was compared between the two groups. RESULTS: Upon admission to Recovery Room, the mean pain severity was not significantly different between the two groups. At one and two hours following surgery the mean pain severity was significantly higher in celecoxib group. However, 6 hours following surgery mean pain severity was higher with meloxicam administration. Pain severity was not significantly different in the two groups, 12 and 24 hours following surgery. CONCLUSION: The analgesic effect of celecoxib seems to cover longer duration than meloxicam; but, meloxicam appears to be a stronger analgesic in shorter time interval.

Short-Term Effects of Adding Topical Ketorolac to Intravitreal Bevacizumab in Diabetic Macular Edema: A Crossover Randomized Clinical Trial.

Purpose: To evaluate the short-term additive effects of topical ketorolac to intravitreal bevacizumab (IVB) in the management of center-involved diabetic macular edema (CI-DME). Methods: In a randomized double-masked placebo-controlled crossover clinical trial, eyes with CI-DME and the best-corrected visual acuity (BCVA) between (20/40) and (20/400) were included. These eyes should have had at least one intravitreal anti-VEGF injection in the preceding two months. They were randomized into two groups; while both groups received two IVB injections with a six-week interval, one group received topical ketorolac every 6 hr in the first interval and artificial tears every 6 hr as a placebo in the second interval and the other group received the same medications using a crossover method. The main outcome measures were changes in BCVA and central macular thickness (CMT). Results: Fifty-seven eyes of 35 patients with CI-DME were included in the study. The mean BCVA improvement was -0.09 ± 0.47 logMAR in the periods of receiving ketorolac and -0.03 ± 0.12 logMAR in the periods of placebo treatment, respectively (P = 0.99). Corresponding changes in CMT were -13.1 ± 170.1 and +11.7 ± 157.7 µm in the ketorolac and placebo periods, respectively (P = 0.322). The treatment effect was not statistically significant regarding both BCVA and CMT changes. Statistical analysis also disclosed that the carryover effect was insignificant for BCVA and CMT. Although the period effect was not significant for BCVA, it was at a meaningful level for CMT changes (P = 0.012). Conclusion: This crossover clinical trial demonstrated that in the course of DME treatment with IVB injections, topical ketorolac did not have any additive beneficial effect at least during a six-week period.

Assessing Survival of Transgenic Bacteria, Serratia AS1 and Enterobacter cloacae, in Sugar Bait, White Saxaul Plant (Haloxylon persicum) and Rodent Barrow's Soil, A Contained-Field Study for Paratransgenesis Approach.

Background: The viability and persistence of engineered bacterium candidates in field conditions is one of the considerable challenges in the paratransgenesis approach to fighting vector-borne diseases. Methods: In this study two engineered bacterium candidates to produce paratransgenic sand flies, Serratia AS1 and Enterobacter cloacae expressing m-Cherry fluorescent were applied on the leaves of the white saxaul plant (Haloxylon persicum), sugar bait, and rodent burrow soil and their persistent time was tested in desert condition, Matin Abad County, Isfahan, August 2022. A PBS suspension of 109 cells/ml was used for sugar bait, spraying on plant leaves (∼10 cm2) and 10 cm2 of rodent burrow soil. Sand fly samples were taken daily and were plated on LB Agar and the fluorescent cells were counted after 24 hours. Results: Time course in general caused a decrease in the number of bacteria for both strains. The two strains were persistent in sugar bait and on plant leaves for four days and on soil for two days. Although there were slight differences between the number of the bacteria in sugar baits, which was not significant (P< 0.05). The number of E. cloacae surviving on plant and in soil were significantly (P< 0.0001 and P= 0.046) higher than Serratia AS1. Conclusion: This study shows that plants or sugar bait are useful routes for delivery of the transformed bacteria for the paratransgenesis approach, although, the bacteria ought to be sprayed on plants or sugar baits should be replaced with new ones in four days intervals.

Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.

Prolonged obstruction of the ureter, which leads to injury of the kidney collecting ducts, results in permanent structural damage, while early reversal allows for repair. Cell structure is defined by the actin cytoskeleton, which is dynamically organized by small Rho guanosine triphosphatases (GTPases). In this study, we identified the Rho GTPase, Rac1, as a driver of postobstructive kidney collecting duct repair. After the relief of ureteric obstruction, Rac1 promoted actin cytoskeletal reconstitution, which was required to maintain normal mitotic morphology allowing for successful cell division. Mechanistically, Rac1 restricted excessive actomyosin activity that stabilized the negative mitotic entry kinase Wee1. This mechanism ensured mechanical G2-M checkpoint stability and prevented premature mitotic entry. The repair defects following injury could be rescued by direct myosin inhibition. Thus, Rac1-dependent control of the actin cytoskeleton integrates with the cell cycle to mediate kidney tubular repair by preventing dysmorphic cells from entering cell division.