Marwan A. Abouammoh

Ranibizumab versus bevacizumab for the treatment of neovascular age-related macular degeneration.

Purpose of review This paper reviews the recent literature regarding the effectiveness, efficacy and safety of intravitreal bevacizumab as compared with ranibizumab for the treatment of neovascular age-related macular degeneration (nAMD). Recent findings Numerous randomized clinical trials have demonstrated the safety and efficacy of ranibizumab for the treatment of nAMD. Bevacizumab, developed, labeled and approved for the management of colorectal cancer, has been used off-label for the management of nAMD. However, given its lower cost and effectiveness, it is commonly used for many cases of nAMD. Recent clinical trials have demonstrated similar effectiveness between the two compounds in terms of visual acuity and central macular thickness. However, emerging data have suggested that these two compounds may have different ocular and systemic adverse event profiles; bevacizumab has been linked to both a higher risk of severe intraocular inflammation and a higher risk of incident arterial thromboembolic events. This incremental risk for both ocular and systemic adverse events may have an impact on the incremental cost–effectiveness ratio derived from health economic models that directly compare one anti-vascular endothelial growth factor (VEGF) compound to the other. Summary Numerous clinical trials, including the Comparison of AMD Treatment Trial, are underway examining the comparative efficacy of ranibizumab versus bevacizumab for the treatment of nAMD. While these studies may demonstrate clinical noninferiority of one anti-VEGF compound over another, they may not be adequately powered to detect important differences in ocular and systemic safety. Large-scale, appropriately powered safety studies need to be conducted to evaluate differences in safety.

High-Mobility Group Box-1 and Endothelial Cell Angiogenic Markers in the Vitreous from Patients with Proliferative Diabetic Retinopathy

The aim of this study was to measure the levels of high-mobility group box-1 (HMGB1) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng levels were significantly higher in PDR patients than in nondiabetics (P = 0.008; <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the whole study group, there was significant positive correlation between the levels of HMGB1, and sVE-cadherin (r = 0.378, P = 0.007). In PDR patients, there was significant negative correlation between the levels of sVE-cadherin and sEng (r = −0.517, P = 0.0005). Exploratory regression analysis identified significant associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95% confidence interval = 6.32–923) and high levels of sEng (odds ratio = 6.01; 95% confidence interval = 1.25–29.0). Our findings suggest that HMGB1, VEGF, sVE-cadherin and sEng regulate the angiogenesis in PDR.

Pars plana vitrectomy with juxtapapillary laser photocoagulation versus vitrectomy without juxtapapillary laser photocoagulation for the treatment of optic disc pit maculopathy: the results of the KKESH International Collaborative Retina Study Group

Background/aims To compare the functional and anatomic outcomes of pars plana vitrectomy (PPV) with juxtapapillary laser photocoagulation (JLP) versus vitrectomy without JLP in optic disc pit maculopathy. Methods This was a multicentre, retrospective study of 46 consecutive patients with optic disc pit maculopathy presenting at tertiary eye centres between 1992 and 2012. Indications for surgery included distorted or decreased vision. Surgical intervention included PPV, posterior vitreous detachment, with or without gas tamponade. Twenty-four patients received laser photocoagulation at the temporal edge of the optic disc pit (group A) and 22 patients had no laser (group B). Postoperative best-corrected visual acuity (BCVA) and optical coherence tomography findings were the main outcome measures. Results Mean follow-up was 44 months (range 12–98 months). BCVA in group A improved significantly from 0.7 logMAR (20/100) preoperatively to 0.5 logMAR (20/60) postoperatively (p=0.017). In group B, BCVA improved from 0.7 logMAR (20/100) preoperatively to 0.4 logMAR (20/40) postoperatively (p=0.014). The difference in final BCVA between groups was not statistically significant (p=0.693). The mean central macular thickness (CMT) in group A improved significantly from 750 μm preoperatively to 309 μm at last follow-up (p<0.0001). The mean CMT in group B improved from 616 μm preoperatively to 291 μm at last follow-up (p=0.028). The difference in final CMT between groups was not statistically significant (p=0.747). Conclusions PPV with JLP for optic disc pit maculopathy had similar functional and anatomic outcomes compared with vitrectomy without JLP.

Ranibizumab injection for diabetic macular edema: meta-analysis of systemic safety and systematic review.

OBJECTIVE To conduct a systematic review on the safety of ranibizumab injections for diabetic macular edema by meta-analysis of recently conducted level 1 randomized clinical trials. DESIGN A meta-analysis and systematic review. METHODS Main outcome measures of permissible studies were extracted and reported. The relative risk (RR) for thromboembolic events (TEEs) was calculated for those studies that met this studys inclusion criteria. The fixed-effects model (Mantel-Haenszel method) was appropriately used to calculate the pooled RR. The quality of trials was assessed using the Jadad score. RESULTS Of the 2072 patients who were included from 5 [corrected] eligible randomized clinical trials, 1295 patients received intravitreal ranibizumab injections. The pooled RR for TEEs after ranibizumab intravitreal injection was 0.74 (95% CI 0.52-1.06). CONCLUSIONS Intravitreal ranibizumab for the treatment of diabetic macular edema did not increase the risk for TEEs as shown by this meta-analysis of 4 randomized, controlled clinical trials.

Multimedia learning tools for teaching undergraduate ophthalmology: results of a randomized clinical study

OBJECTIVE To evaluate the effectiveness of a novel multimedia learning tool (MMLT) for teaching a method of approaching common ophthalmologic presentations. DESIGN Randomized clinical study. PARTICIPANTS 25 second-year medical students at Queens University. METHODS We evaluated 2 MMLTs pertaining to common ophthalmologic presentations--acute visual loss and cataract--through the use of a randomized clinical study. Subjects were randomized either to watch a short-form video or to read a textbook excerpt for both cataract and acute visual loss. If randomized to one MMLT for the first module, the subject was allocated to the other modality for the second module. The main outcomes of interest were knowledge retention as measured by a short multiple-choice questionnaire, efficiency, and user preference. RESULTS A trend was noted whereby subjects randomized to an MMLT had higher composite scores on multiple-choice questionnaires (mean score MMLT = 75.2% vs text = 67.5%; t test = 1.535; df = 22; p value = 0.139). Additionally, those who watched an MMLT spent 72% less time reviewing the education content (29 min vs 8 min; t test = 3.955, p value = 0.0003). Of the sample, 87% preferred the MMLT over the text. CONCLUSIONS MMLTs can significantly reduce learning time without sacrificing knowledge retention in undergraduate students of ophthalmology.

Iris Neovascularization and Neovascular Glaucoma in Neurofibromatosis Type 1: Report of 3 Cases in Children

Purpose:To report the clinical findings and outcomes in 3 patients with neurofibromatosis 1 (NF1) and retinal vascular abnormalities that resulted in angle closure secondary to iris neovascularization and describe the histopathologic abnormalities in 1 case. Patients and Methods:Retrospective case series of patients with NF1 and angle closure due to iris neovascularization secondary to retinal vascular abnormalities. Histopathologic analysis of an enucleated eye in 1 case. Results:Three children whose age ranged from 5 to 10 years at presentation, developed unilateral retinal vascular abnormalities that resulted in iris neovascularization and angle closure with a wide range of intraocular pressures. Two patients had retinal vasoproliferative lesions of which the affected eye became blind in 1 patient and the other retained useful vision after treatment with intracameral Bevacizumab, ablation of the retinal lesions, and surgical treatment of the neovascular glaucoma. The third patient underwent enucleation and had pathologic evidence of retinal ischemia. Conclusions:A variety of retinal vascular lesions occurring in NF1 are capable of producing iris neovascularization, ectropion uvea, and neovascular glaucoma. Although a spectrum of serious complications resulting in total vision loss can occur, retention of useful vision is possible, in some cases, with aggressive treatment of the retinal lesions and associated neovascular glaucoma. This report highlights the need for careful examination of the posterior segment with special attention to peripheral retinal vascular abnormalities or tumors in young patients with NF1.

Macular hole in Behçet's disease

Objective: To investigate the clinical features, prevalence, role of surgical intervention and the visual prognosis of macular holes (MH) in patients with Behcets disease (BD). Materials and Methods: Retrospective study of patients with BD and MH from January 1998 to November 2008. Results: Out of 159 patients, 21 eyes of 17 patients were identified with MH. The mean age was 38.59 (range 23-61) years and the mean follow-up period was 5.1 years (range 13-164 months). The prevalence of MH was 7%. Visual acuity (VA) at the time of presentation ranged from 20/70 to hand-motion. Optical coherence tomography (OCT) findings revealed intraretinal cysts at the edge of the MH. The mean size of MH was 983.6 um; 52% had elevated edges, 43% had flat edges and only one eye (5%) was closed postoperatively. Fluorescein angiography (FA) was consistent with macular ischemia in 76% of the cases. Human leukocyte antigen (HLA) B51 association was found in 14 of the 15 patients investigated. Six patients (out of 17) underwent pars plana vitrectomy. The final VA on their last follow-up ranged from 20/70 to 2/200. Surgical intervention for MH did not result in any visual improvement as compared to non-operated eyes. One patient lost vision completely due to elevated intraocular pressure post vitrectomy and silicon oil tamponade. Conclusions: MH in patients with BD may lead to significant visual disability. Surgical intervention does not seem to have any potential beneficial effect on the VA, probably due to significant macular ischemia and sequelae from the ocular inflammation.

Advances in the treatment of central serous chorioretinopathy

Central serous chorioretinopathy is a disease that is partly understood. Novel advancements have led to further understanding of the disease, and have identified choroidal dysfunction as the principal element in CSCR development. New imaging tools have aided in better monitoring disease response to various treatment models. Enhanced depth imaging optical coherence tomography, in particular, has helped in observing choroidal thickness changes after various treatment models. To date, photodynamic therapy and focal laser remain the main stay of treatment. More understanding of disease pathophysiology in the future will help in determining the drug of choice and the best management option for such cases.

Novel drugs and their targets in the potential treatment of diabetic retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes. It causes vision loss, and the incidence is increasing with the growth of the diabetes epidemic worldwide. Over the past few decades a number of clinical trials have confirmed that careful control of glycemia and blood pressure can reduce the risk of developing DR and control its progression. In recent years, many treatment options have been developed for clinical management of the complications of DR (e.g., proliferative DR and macular edema) using laser-based therapies, intravitreal corticosteroids and anti-vascular endothelial growth factors, and vitrectomy to remove scarring and hemorrhage, but all these have limited benefits. In this review, we highlight and discuss potential molecular targets and new approaches that have shown great promise for the treatment of DR. New drugs and strategies are based on targeting a number of hyperglycemia-induced metabolic stress pathways, oxidative stress and inflammatory pathways, the renin-angiotensin system, and neurodegeneration, in addition to the use of stem cells and ribonucleic acid interference (RNAi) technologies. At present, clinical trials of some of these newer drugs in humans are yet to begin or are in early stages. Together, the new therapeutic drugs and approaches discussed may control the incidence and progression of DR with greater efficacy and safety.

Indocyanine green angiographic findings in initial-onset acute Vogt-Koyanagi-Harada disease.

To study the features of Indocyanine green angiography (ICGA) in patients with initial‐onset acute Vogt–Koyanagi–Harada (VKH) disease.