Management of Diabetic Macular Edema: Guidelines from the Emirates Society of Ophthalmology.

In the United Arab Emirates, retinopathy has been shown to be present in 19% of the diabetic population, with diabetes identified in up to 40% of individuals aged over 55 years. Despite the prevalence of diabetic retinal diseases, there are no unified national guidelines on the management of diabetic macular edema (DME). These published guidelines are based on evidence taken from the literature and published trials of therapies, and consensus opinion of a representative expert panel with an interest in this condition, convened by the Emirates Society of Ophthalmology. The aim is to provide evidence-based, clinical guidance for the best management of different aspects of DME, with a special focus on vision-threatening diabetic retinopathy. Treatment should be initiated in patients with best-corrected visual acuity 20/30 or worse, and/or features of DME as seen on optical coherence tomography (OCT) with central retinal thickness (CRT) of at least 300 µm or in symptomatic patients with vision better than 20/25, and/or CRT less than 300 µm where there are OCT features consistent with center-involving macular edema. The treatment of DME is effective irrespective of glycated hemoglobin (HbA1c) level, and treatment must not be denied or delayed in order to optimize systemic parameters. All ophthalmic treatment options should be discussed with the patient for better compliance and expectations. Non-center-involving DME can be initially observed until progression toward the center is documented. Macular laser no longer has a primary role in center-involving DME, and anti-vascular endothelial growth factor (anti-VEGF) therapy should be considered as first-line treatment for all patients, unless contraindicated. If anti-VEGF is contraindicated, a steroid dexamethasone implant can be considered for first-line treatment. Recommendations for the treatment of DME in special circumstances and in relapsing and refractory DME are also discussed.

Treatment patterns in patients with age-related macular degeneration and diabetic macular edema: A real-world claims analysis in Dubai.

OBJECTIVES: To characterize the pattern of approved anti-vascular endothelial growth factor (VEGF) treatments among patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in the United Arab Emirates (UAE). METHOD: This was a retrospective, nonrandomized, observational cohort analysis of the Dubai Real-world Claims Database with a 360-day follow-up period. Adult patients diagnosed with nAMD or DME treated with ranibizumab or aflibercept for the first time were included. The primary objective was to evaluate anti-VEGF treatment patterns with respect to the proportion of patients receiving ranibizumab and aflibercept for nAMD and DME separately. RESULTS: Of the 451 patients included in the final study cohort, 83.6% and 16.4% had a diagnosis of DME (ranibizumab: 48.5%; aflibercept: 51.5%) and nAMD (ranibizumab: 40.5%; aflibercept: 59.5%), respectively, at baseline. Treatment frequency of ranibizumab/aflibercept was similar for nAMD (mean: 2.4/2.9 injections; p = 0.2389) with fewer injections in the ranibizumab cohort for DME (mean: 1.9/2.5 injections; p = 0.0002). Most patients received ≤3 anti-VEGF injections during the 360-day follow-up period. The time between consecutive treatments was large (nAMD: 73.6 days/10.5 weeks; DME: 80.5 days/11.5 weeks). Approximately 10%-13.5% of patients switched their anti-VEGF therapy. Most patients (83.8%) had a diabetes diagnosis during the follow-up period. CONCLUSIONS: This real-world study provides an initial understanding of anti-VEGF treatment patterns in patients with nAMD and DME in the UAE. Treatment frequency of the 2 anti-VEGF agents assessed was similar in both patient populations. Both treatments were infrequently administered with large dosing intervals.

Change in cardiac troponin T level after intravitreal anti-vascular endothelial growth factor treatment: Prospective pilot study.

BACKGROUND: Evaluate subclinical myocardial injury associated with intravitreal anti-vascular endothelial growth factor therapy by measuring serum high-sensitivity cardiac troponin T. METHODS: This is a prospective pilot comparative study conducted at American University of Beirut Medical Center, Beirut, Lebanon. In total, 40 consecutive patients were randomized to receive either intravitreal bevacizumab or ranibizumab. Patients received three consecutive monthly injections of the assigned drug, then continued treatment as needed. Systemic concentrations of high-sensitivity cardiac troponin T and vascular endothelial growth factor were obtained at baseline, week 9, and week 24. Primary endpoint measure was change in high-sensitivity cardiac troponin T levels compared to baseline. Secondary endpoint measure was change in systemic vascular endothelial growth factor levels. RESULTS: There was no significant difference in high-sensitivity cardiac troponin T levels over time (p = 0.227) within each treatment group and no significant difference between treatments at any time point (p = 0.276). There was a significant decrease in plasma vascular endothelial growth factor levels at week 9 (p = 0.001) and week 24 (p < 0.001) compared to baseline. In the ranibizumab group, vascular endothelial growth factor levels were not significantly different at weeks 9 and 24 compared to baseline (p = 0.708 and p = 0.117, respectively). There was a significant association between the number of bevacizumab injections from weeks 8 to 24 and the decrease in vascular endothelial growth factor levels at week 24 (R = -0.67, p = 0.032). This correlation was not observed in the ranibizumab group (R = -0.341, p = 0.141). CONCLUSION: Repeated intravitreal bevacizumab or ranibizumab did not influence serum high-sensitivity cardiac troponin levels. Intravitreal bevacizumab but not ranibizumab lowered free-systemic vascular endothelial growth factor levels, which was observed in this study to be inversely related to the number of bevacizumab injections.

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

PURPOSE: To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. METHODS: Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. RESULTS: Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 µm to 236.2 µm, occurred 1 month after dexamethasone implant (P < 0.0001). By Month 6, mean central retinal thickness was 287.3 µm (P = 0.16). Eyes with only intraretinal fluid (13 eyes) achieved a fluid-free macula. Eyes with predominantly subretinal fluid (6 eyes) did not improve central retinal thickness and continued monthly ranibizumab. Mean baseline intraocular pressure was 13.2 mmHg, which peaked at 15.6 mmHg by Month 2 (P = 0.004). CONCLUSION: Intravitreal dexamethasone implant improved only macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Induction with intravitreal bevacizumab every two weeks in the management of neovascular age-related macular degeneration.

PURPOSE: To explore the benefit of rapid induction with intravitreal bevacizumab for neovascular age-related macular degeneration (AMD). DESIGN: Single-institution prospective randomized pilot study. METHODS: Patients with treatment-naïve neovascular AMD were randomized 1:1:1 into 1 of 3 groups based on the induction sequence: (1) every 2 weeks for 3 consecutive injections; (2) every 4 weeks for 3 consecutive injections; and (3) immediate pro re nata (prn) after the first injection. Retinal angiomatous proliferation and polypoidal choroidal vasculopathy were excluded. Best-corrected visual acuity (BCVA) and central retinal thickness using optical coherence tomography (OCT) were measured at baseline and at each follow-up. After induction, bevacizumab was administered as needed based mainly on OCT. Main outcome measure was mean initial fluid-free interval after induction. Secondary outcomes were mean improvement in BCVA and central retinal thickness. RESULTS: Each group included 30 patients (30 eyes). Mean initial fluid-free interval was 2.4, 3.4, and 3.5 months for biweekly induction, monthly induction, and immediate prn groups, respectively (P = .03). Significance was lost when corrected for age and sex (P = .073). Mean improvement in BCVA, central retinal thickness, and total number of injections were similar among the groups at 12 months. Six eyes in the biweekly induction group developed subretinal fibrosis vs no eyes in the other 2 groups (P = .003). CONCLUSION: Biweekly induction with intravitreal bevacizumab for treatment-naïve neovascular AMD does not increase initial fluid-free interval or cause significant anatomic and functional benefit compared to monthly induction or immediate prn. There is also the potential development of subretinal fibrosis with biweekly induction.

Comparative effectiveness analysis of anticoagulant strategies in a large observational database of percutaneous coronary interventions.

BACKGROUND: Percutaneous coronary intervention (PCI) is the most commonly used procedure for coronary revascularization. There are multiple adjuvant anticoagulation strategies available. In this era of cost containment, we performed a comparative effectiveness analysis of clinical outcomes and cost of the major anticoagulant strategies across all types of PCI procedures in a large observational database. METHODS: A retrospective, comparative effectiveness analysis of the Premier observational database was conducted to determine the impact of anticoagulant treatment on outcomes. Multiple linear regression and logistic regression models were used to assess the association of initial antithrombotic treatment with outcomes while controlling for other factors. RESULTS: A total of 458,448 inpatient PCI procedures with known antithrombotic regimen from 299 hospitals between January 1, 2004 and March 31, 2008 were identified. Compared to patients treated with heparin plus glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin was associated with a 41% relative risk reduction (RRR) for inpatient mortality, a 44% RRR for clinically apparent bleeding, and a 37% RRR for any transfusion. Furthermore, treatment with bivalirudin alone resulted in a cost savings of $976 per case. Similar results were seen between bivalirudin and heparin in all end-points. Combined use of both bivalirudin and GPI substantially attenuated the cost benefits demonstrated with bivalirudin alone. CONCLUSION: Bivalirudin use was associated with both improved clinical outcomes and decreased hospital costs in this large "real-world" database. To our knowledge, this study is the first to demonstrate the ideal comparative effectiveness end-point of both improved clinical outcomes with decreased costs in PCI.

The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration.

PURPOSE: The purpose of this article is to evaluate the effect of nicotine on anti-vascular endothelial growth factor therapy in the treatment of neovascular age-related macular degeneration. METHODS: One group of mice received nicotine in drinking water and the other group received water only. Choroidal neovascularization (CNV) was induced with a laser. Nicotinic acetylcholine receptor-α7 (nAChRα7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 postlaser, and the effects were evaluated on Days 14 and 21. α-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14. RESULTS: Expression of nAChRα7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and α-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas α-bungarotoxin did have an effect. Comparing water- and nicotine-fed mice, CNV size was 61% to 86% smaller in water-fed mice except for the α-bungarotoxin group, where there was no difference. Platelet-derived growth factor and vascular endothelial growth factor expression was 1.5- to 2.5-fold higher at Day 14 in nicotine-treated mice. CONCLUSION: Nicotine significantly blocks the effect of anti-vascular endothelial growth factor therapy in the treatment of laser-induced neovascular age-related macular degeneration. nAChRα7 is significantly upregulated during the formation of CNV, and treatment with an nAChRα7 antagonist decreases CNV size irrespective of nicotine administration.

The effect of povidone iodine flush versus drops on conjunctival colonization before intravitreal injections.

BACKGROUND: To determine the most effective method of applying povidone iodine 5% to decrease conjunctival colonization before intravitreal injections. METHODS: Twenty-eight patients from two tertiary care centers undergoing intravitreal injection for diffuse diabetic macular edema, exudative age-related macular degeneration, venous occlusive disease, or refractory pseudophakic cystoid macular edema were prospectively randomized to two study arms. One arm received 2-3 drops of 5% povidone iodine (drops group) and the second received a 10 ml flush of the same solution (flush group). The inferior conjunctival fornix was cultured before and after antiseptic technique was performed in all patients. Three culture media, thioglycollate broth, chocolate agar and blood agar, were used for each sample. RESULTS: Each study group had 14 patients. Prior to antisepsis, 22 of the 28 (78.6%) subjects had positive conjunctival cultures. 16 and 14 bacterial organisms were isolated in the first and second groups, respectively. After using 2-3 drops of 5% povidone iodine in the first study arm of patients, three of 16 (18.7% reduction) bacterial organisms were no longer isolated in thioglycollate broth media. With flush irrigation of 10 ml of 5% povidone iodine, seven of 14 (50% reduction) bacterial organisms were no longer isolated (P-value 0.07) in broth media. No difference in reduction of bacterial colonization was found on plated media (chocolate agar and blood agar). CONCLUSIONS: Irrigating the conjunctival fornix with 5% povidone iodine results in greater reduction of bacterial colonization compared with drop application of the same solution. Flush irrigation may provide better protection against the risk of endophthalmitis with intravitreal injections.