Alireza Ramezani

Randomized Trial of Intravitreal Bevacizumab Alone or Combined with Triamcinolone versus Macular Photocoagulation in Diabetic Macular Edema

PURPOSE To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME). DESIGN Randomized 3-arm clinical trial. PARTICIPANTS A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment. METHODS The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated. MAIN OUTCOME MEASURES Change in best-corrected visual acuity (VA) at week 24. RESULTS VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively. CONCLUSIONS Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

INTRAVITREAL BEVACIZUMAB (AVASTIN) INJECTION ALONE OR COMBINED WITH TRIAMCINOLONE VERSUS MACULAR PHOTOCOAGULATION AS PRIMARY TREATMENT OF DIABETIC MACULAR EDEMA

Purpose: To report the efficacy of a single intravitreal bevacizumab injection alone or in combination with intravitreal triamcinolone acetonide versus macular laser photocoagulation (MPC) as primary treatment of diabetic macular edema (DME). Methods: In this randomized, three-arm clinical trial, 103 eyes of 97 patients with clinically significant DME and no previous treatment were enrolled. The eyes were randomly assigned to one of three study arms: the intravitreal bevacizumab (IVB) group, patients who received 1.25 mg of intravitreal bevacizumab (37 eyes); the IVB/IVT group, patients who received 1.25 mg of intravitreal bevacizumab and 2 mg of intravitreal triamcinolone (33 eyes); and the MPC group, patients who underwent focal or modified grid laser (33 eyes). Primary outcome measure was change in visual acuity. Results: Visual acuity changes ± SD at 12 weeks were −0.22 ± 0.23, −0.13 ± 0.31, and + 0.08 ± 0.31 logarithm of the minimal angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively. The marginal regression model based on generalized estimating equation analysis demonstrated that the visual acuity changes in the groups were statistically significant at both 6 weeks (P < 0.0001) and 12 weeks (P = 0.024). The significant treatment effect was demonstrated at both 6 weeks and 12 weeks in the IVB group and only at 6 weeks in the IVB/IVT group. Significant central macular thickness (CMT) reduction was observed in eyes in the IVB and IVB/IVT groups only up to 6 weeks; however, CMT changes were not significant in the groups. Conclusion: Up to 12 weeks, intravitreal bevacizumab treatment of patients with DME yielded better visual outcome than laser photocoagulation, although it was not associated with a significant decrease in CMT. No further beneficial effect of intravitreal triamcinolone could be demonstrated. Further clinical trials with longer follow-up are required to evaluate the long-term visual outcomes and complication profiles after primary treatment with such medications.

Randomized Trial of Intravitreal Clindamycin and Dexamethasone versus Pyrimethamine, Sulfadiazine, and Prednisolone in Treatment of Ocular Toxoplasmosis

PURPOSE To compare the efficacy of intravitreal injection of clindamycin and dexamethasone with classic treatment for ocular toxoplasmosis. DESIGN Prospective, randomized single-masked clinical trial. PARTICIPANTS A total of 68 patients with active ocular toxoplasmosis were assigned randomly to 2 treatment groups: 34 in the intravitreal clindamycin plus dexamethasone (IVCD) group and 34 in the classic treatment (CT) group. INTERVENTION The IVCD group received 1 to 3 injection(s) of 1 mg intravitreal clindamycin and 400 μg dexamethasone, and the CT group received 6 weeks of treatment with pyrimethamine and sulfadiazine plus prednisolone. Antitoxoplasmosis antibodies (immunoglobulin [Ig] M and IgG) were measured using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES Changes in retinochoroidal lesion size, measured by a computer program written in the MATLAB environment, 6 weeks after initiation of treatment. Visual acuity (VA) changes, vitreous inflammatory response, adverse drug reactions, and rate of recurrence were secondary outcome measures. RESULTS The mean number of injections in the IVCD group was 1.6. The lesion size reduction was statistically significant after treatment in both IVCD and CT groups (P < 0.001 and P = 0.009, respectively). However, the difference in mean percentage of reduction at 6 weeks was not significant: 57.0 ± 27.8% in the IVCD group versus 58.4 ± 29.3% in the CT group (P = 0.569). In relation to the baseline, VA increased by 0.44 ± 0.24 and 0.29 ± 0.19 logarithm of the minimum angle of resolution units in the IVCD and CT groups, respectively (P < 0.001); however, the difference of VA improvement between the groups was not significant. The interaction effect of IgM and treatment group on lesion size reduction was significant (P = 0.002); this indicated that IgM-positive cases responded better to CT and IgM-negative cases responded better to IVCD treatment. Vitreous inflammation reduction was insignificant between the groups. Within 2 years, 4 eyes (2 in each group) had 1 episode of recurrence. Adverse drug reactions occurred in 2 patients in the CT group. No major injection-related complication was encountered in the IVCD group. CONCLUSIONS Intravitreal injection of clindamycin and dexamethasone may be an acceptable alternative to the classic treatment in ocular toxoplasmosis. It may offer the patient more convenience, a safer systemic side effect profile, greater availability, and fewer follow-up visits and hematologic evaluations.

Two-year results of a randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus laser in diabetic macular edema.

Purpose The purpose of this study was to report the 24-month findings of a randomized clinical trial comparing intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment for diabetic macular edema. Methods The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB; the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT; and the MPC group, patients who underwent focal or modified grid laser. Of 150 eyes (50 in each group) in the primary trial, 123, 119, and 113 eyes completed follow-ups at 12, 18, and 24 months, respectively. A total of 39 (78%), 36 (72%), and 38 (76%) eyes in the IVB, IVB/IVT, and MPC groups remained in the study within 24 months, respectively. Retreatment was performed at 3-month intervals whenever indicated. Data from a 24-month follow-up are presented. Changes in best-corrected visual acuity and central macular thickness up to 24 months were the main outcome measures in this study. Results Retreatment was required in 37 (94.9%), 27 (75.0%), and 31 (81.6%) eyes, respectively, in the IVB, IVB/IVT, and MPC groups up to 24 months. The significant superiority of visual acuity improvement in the IVB group, which had been noted at Month 6, did not sustain thereafter up to 24 months, and the difference among the groups was not significant at all visits. However, the mean visual acuity improvement was greater in the IVB group than the other groups and in the IVB/IVT group compared with the MPC group. The reduction of central macular thickness was more in the IVB group in relation to the other two treatment groups; however, the difference among the groups was not statistically significant at any of the follow-up visits. Conclusion In terms of vision improvement, the significant superiority of the IVB over the combined IVB/IVT and MPC treatment that had been observed at Month 6 did not sustain up to 24 months. This means that although IVB treatment may be a better choice than two other options in short term, the magnitude of this beneficial effect diminishes over time.

Pilot study of intravitreal injection of diclofenac for treatment of macular edema of various etiologies.

Purpose: The purpose of this study was to evaluate the effect of a single dose of intravitreal diclofenac, a potent nonsteroidal antiinflammatory drug, on visual acuity and central macular thickness in patients with macular edema of various etiologies. Methods: In this prospective noncomparative case series, 10 eyes of 10 patients with clinically significant diabetic macular edema (n = 5), neovascular age-related macular degeneration (n = 2), pseudophakic cystoid macular edema (n = 1), macular edema secondary to old branch retinal vein occlusion (n = 1), and cystoid macular edema secondary to chronic intermediate uveitis (n = 1) received 500 &mgr;g/0.1 mL of intravitreal diclofenac. The primary outcome measure was change in visual acuity. Results: After 2 weeks, visual acuity improved in 3 (30%) eyes (P = 0.78), did not change in 3 (30%) eyes, and decreased in 3 (30%) eyes. After 4 weeks, improvement of best-corrected visual acuity occurred in 5 (50%) eyes (P = 0.07), but in 3 eyes (30%), best-corrected visual acuity did not change, and in 1 eye (10%), visual acuity decreased. After 8 weeks, visual acuity improved in 7 (70%) eyes (P = 0.019), got worse in 1 eye (10%), and did not change in 2 eyes (20%). Central macular thickness did not decrease significantly at 8 weeks. On the basis of electroretinography, no significant changes in the amplitude of a-wave or b-wave in relation to baseline were noticed in any eye. Conclusion: Up to 8 weeks, intravitreal diclofenac treatment of eyes with macular edema of various etiologies yielded prominent improvement in visual acuity but was not associated with a significant decrease in central macular thickness. No toxic effect of intravitreal diclofenac was observed.

Triamcinolone acetonide in silicone-filled eyes as adjunctive treatment for proliferative vitreoretinopathy : a randomized clinical trial

OBJECTIVE To evaluate the effect of adjunctive intraocular triamcinolone acetonide (TA) in silicone-filled eyes on outcomes of vitreoretinal surgery for proliferative vitreoretinopathy (PVR). DESIGN Prospective, randomized, controlled clinical trial. PARTICIPANTS Seventy-five eyes with rhegmatogenous retinal detachment and PVR grade C (posterior, anterior, or both) undergoing vitrectomy combined with silicone oil tamponade were included. Of these, 38 eyes were assigned randomly to the adjunctive treatment, whereas 37 eyes served as controls. INTERVENTION All eyes underwent pars plana vitrectomy, membrane peeling, and silicone oil exchange, with or without relaxing retinotomy or retinectomy. In the treatment group, 4 mg TA was injected into the silicone-filled vitreous cavity at the end of the procedure. Silicone oil was removed 3 months after surgery in eyes with attached retinas. MAIN OUTCOME MEASURES The primary outcome measure was retinal reattachment rate at 6 months. Secondary outcome measures included visual acuity, rate of recurrent PVR, reoperation rate, and rise of intraocular pressure. RESULTS Retinal reattachment without any reoperation was achieved in 32 eyes (84.2%) and 29 eyes (78.4%) in the adjunctive treatment and control groups, respectively, at 6 months (P = 0.5). No statistically significant difference was observed between the 2 groups in terms of any of the secondary outcome measures (P>0.05). CONCLUSIONS The outcomes of vitreoretinal surgery for established PVR are not improved significantly by adjunctive TA injection in silicone-filled eyes.

Intravitreal Bevacizumab Versus Triamcinolone Acetonide for Refractory Uveitic Cystoid Macular Edema: A Randomized Pilot Study

PURPOSE To compare intravitreal bevacizumab (IVB) versus intravitreal triamcinolone acetonide (IVT) for treatment of refractory uveitic cystoid macular edema (CME). METHODS In this randomized clinical trial, 31 eyes with uveitic CME were allocated into the IVB group-eyes that received 1-3 injections of 1.25 mg bevacizumab (15 eyes) and the IVT group-eyes that received 1-3 injections of 2 mg triamcinolone (16 eyes). Primary outcome measure was change in best-corrected visual acuity (VA) at 36 weeks. RESULTS Visual acuity improvement compared with baseline values was meaningful in the IVB group at 12, 24, and 36 weeks (-0.35 + or - 0.45 logMAR [P = 0.016]) and in the IVT group at 24 and 36 weeks (-0.32 + or - 0.32 logMAR [P = 0.001]). A significant central macular thickness (CMT) reduction was observed only in the IVT group at week 36 (74.6 + or - 108.0 microm [P = 0.049]). Between-group analysis disclosed no significant difference in any outcome measure. By statistically removing the factor of cataract, the IVT group had more improvement in VA (P = 0.007). CONCLUSIONS IVB was as effective as IVT in refractory uveitic CME regarding VA improvement up to 36 weeks. Irrespective of triamcinolone-induced cataract, a more beneficial effect of IVT may be attainable.

Clinical Features and Surgical Outcomes of Pediatric Rhegmatogenous Retinal Detachment

Purpose: To evaluate the clinical features and functional and anatomical outcomes after surgical intervention in pediatric rhegmatogenous retinal detachment. Methods: In this retrospective case series, pediatric patients with rhegmatogenous retinal detachment who had surgical intervention were included. Cases were categorized into five main etiology groups: congenital or developmental (48 eyes); trauma (54 eyes); myopia alone (12 eyes); previous intraocular surgery (10 eyes); and miscellaneous (3 eyes). Patients‘ demographic, clinical, and surgical outcomes, as well as fellow eye findings were evaluated. Results: One hundred twenty-seven eyes of 108 patients (mean age: 12.1 ± 4.1 year, 80.6% male) were included. Scleral buckling was the initial procedure in 31% of eyes and vitrectomy in 63%. Mean follow-up was 34 ± 21 months (median 33 months). Retinal reattachment at last follow-up was achieved in 74.9% of eyes. Visual acuity was ≥20/200 in 14% of eyes preoperatively and in 47.9% of eyes at final follow-up (P = 0.001). Retinal pathologies (mostly lattice degeneration) were noted in 82.2% of fellow eyes. Conclusion: Trauma and congenital-developmental anomalies were the leading etiologies in pediatric rhegmatogenous retinal detachment in this review. Despite the complexity of rhegmatogenous retinal detachment and presence of vision-threatening anomalies, anatomic and functional outcomes were acceptable. Regular ophthalmoscopy of the sound eye is recommended for children at risk.

Posterior sub-tenon triamcinolone for refractory diabetic macular edema: a randomized clinical trial.

Purpose To evaluate the effect of posterior sub-tenon triamcinolone acetonide (TA) injection on clinical, angiographic, and optical coherence tomographic (OCT) parameters in refractory diabetic macular edema (DME). Methods In a double-masked placebo-controlled clinical trial, 64 eyes were randomly assigned to two groups. The treatment group (32 eyes) received 40 mg posterior sub-tenon injection of TA and the placebo group (32 eyes) received subconjunctival injection of a placebo. The injections were repeated after 2 months in both groups. Complete ophthalmologic examination, fluorescein angiography, and OCT were performed before intervention and after 4 months. Quantitative measurement of angiographic variables such as the amount of hard exudates (HE), size of foveal avascular zone (FAZ), and leakage severity was performed by computer, using Photoshop software. Results Initial best-corrected visual acuity (VA) was 0.93±0.39 logMAR in the placebo group and 0.75±0.38 logMAR in the treatment group. At 4 months, corrected VA was 0.88±0.48 logMAR in the controls versus 0.71±0.42 logMAR in the cases. Mean central macular thickness measured by OCT before and 4 months after injection was 392 and 377 microns in the treatment group and 388 and 357 microns in the placebo group, respectively. No statistically significant difference was detected between the two groups. The difference was also not significant in HE, FAZ, and leakage in the angiograms. Conclusions Two injections of posterior sub-tenon TA had no therapeutic effect on refractory DME.

Effect of tranexamic acid on early postvitrectomy diabetic haemorrhage; a randomised clinical trial

Aims: To evaluate the effect of tranexamic acid on early postvitrectomy haemorrhage in diabetic patients. Methods: In a clinical trial, 62 diabetic patients scheduled for vitrectomy were randomly assigned to two groups. The treatment group (32 eyes) received two doses of tranexamic acid (10 mg/kg) shortly before and after the operation intravenously, continued orally for 4 days (20 mg/kg/8 hours). The control group (30 eyes) received no medication. Both media clarity and visual acuity were compared during 4 weeks. Results: Four weeks after surgery visual acuity was low (⩽1 metre counting fingers) in 21.4%, moderate (>1 metre counting fingers but<20/200) in 14.3%, and good (⩾20/200) in 64.3% of the treated group. Corresponding figures in the control group were 26.1%, 26.1%, and 47.8%, respectively. These differences were of no statistical significance. The ratio of mild to severe vitreous haemorrhage during the first 4 days and after 4 weeks was 79% to 21% and 82% to 18% in the treatment group and 76.7% to 23.3% and 78.3% to 21.7% in the control group respectively, which showed no statistically significant difference. Conclusion: Tranexamic acid, with the method of administration in this study, had no effect on reducing early postvitrectomy haemorrhage in diabetic patients.