Mohammad Ali Sadiq

Endogenous endophthalmitis: diagnosis, management, and prognosis

Endogenous endophthalmitis is an ophthalmic emergency that can have severe sight-threatening complications. It is often a diagnostic challenge because it can manifest at any age and is associated with a number of underlying predisposing factors. Microorganisms associated with this condition vary along a broad spectrum. Depending upon the severity of the disease, both medical and surgical interventions may be employed. Due to rarity of the disease, there are no guidelines in literature for optimal management of these patients. In this review, treatment guidelines based on clinical data and microorganism profile have been proposed.

Novel Therapies in Development for Diabetic Macular Edema.

Diabetic macular edema (DME) secondary to diabetic retinopathy (DR) is a major cause for functional visual loss in the developed world. Laser photocoagulation has been used for decades in the treatment of DME. However, the advent of anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment of DME. Three important anti-VEGF agents whose efficacy has been well established via phase III clinical trials include ranibizumab, bevacizumab, and aflibercept. However, even in the era of anti-VEGF therapies, there are some challenges that retina specialists have to confront in managing patients with DME. These include the need for frequent treatment and an unpredictable response to therapy. There is evidence to suggest that pathways other than the VEGF pathway may be playing a role in the development of DME. Thus, extensive research is focused on development of novel agents that target these pathways. This review focuses on novel therapeutic agents in development, which may be used as a monotherapy or in combination with anti-VEGF agents, for the management of DME in the future.

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described.

Vascular endothelial growth factor trap-eye (Aflibercept) for the management of diabetic macular edema

Diabetic retinopathy (DR) is the most common cause of visual loss among working age individuals. Diabetic macular edema (DME) is an important complication of DR that affects around one third of the patients with DR. Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor (VEGF) antagonists. The index review discusses aflibercept (EYLEA(®)-Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, and Bayer Healthcare Pharmaceuticals, Berlin, Germany) in the context of other VEGF antagonists currently available for the treatment of DME. A systematic search of literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication. Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A (VEGF-A) along with a longer duration of action as compared to other VEGF antagonists. Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring. Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases. However, further studies are indicated to confirm the role, safety, and efficacy of aflibercept for DME.

Platelet derived growth factor inhibitors: A potential therapeutic approach for ocular neovascularization

Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy (DR), retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factor (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF plays an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly AMD, has become more exciting due to agents such as PDGF antagonists.

Month-6 primary outcomes of the READ-3 study (Ranibizumab for Edema of the mAcula in Diabetes-Protocol 3 with high dose).

PurposeTo compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME) and a central subfield thickness (CFT) of ≥250 μm on time-domain optical coherence tomography.DesignRandomized, controlled, multicenter clinical trial.MethodsEligible eyes were randomized in a 1:1 ratio to 0.5 mg (n=77) or 2.0 mg (n=75) RBZ. Study eyes received 6-monthly injections.Main outcome measuresThe primary outcome measure was the mean change in best corrected visual acuity (BCVA) at month 6. Secondary outcomes included the incidence and severity of systemic and ocular adverse events and the mean change in CFT from baseline.ResultsIn all, 152 eyes (152 patients) were randomized in the study. At month 6, the mean improvement from baseline BCVA was +9.43 letters in the 0.5 mg RBZ group and +7.01 letters in the 2.0 mg RBZ group (P=0.161). At month 6, one death occurred in the 0.5 mg RBZ group and three deaths in the 2.0 mg RBZ group, all due to myocardial infarction in subjects with a prior history of heart disease. Mean CFT was reduced by 168.58 μm in the 0.5 mg RBZ group and by 159.70 μm in the 2.0 mg RBZ group (P=0.708).ConclusionsThere was no statistically significant difference in the mean number of letters gained between the 0.5 and 2.0 mg RBZ groups through month 6. In this DME study population, high-dose RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

Fundus autofluorescence imaging: Fundamentals and clinical relevance

Fundus autofluorescence (FAF), a relatively new imaging modality, focuses on the fluorescent properties of pigments in the retina to generate images that help us view various disease processes from a different perspective. It aids us in the understanding of the pathophysiology of different retinal disorders. Recently, FAF imaging is being used commonly to help us in the diagnosis, prognosis as well as in determining the treatment response of various retinal disorders. It generates an image based on the distribution pattern of a fluorescent pigment called lipofuscin. Knowing the distribution pattern of lipofuscin in the normal retina is key to understanding an FAF image representing a retinal pathology. Like most other imaging modalities, FAF comes with its own limitations, taking steps to overcome these limitations will be of utmost importance in using this imaging modality to its fullest potential.

Emixustat and Lampalizumab: Potential Therapeutic Options for Geographic Atrophy

Two novel classes of medications are currently under extensive investigation for the treatment of dry age-related macular degeneration (AMD). Emixustat, an orally administered visual cycle inhibitor, and lampalizumab, an intravitreally administered monoclonal body directed against complement factor D, have shown promise in phase 2 clinical trials in the treatment of nonneovascular (dry) AMD. Lampalizumab is currently being evaluated in a large, multicenter, phase 3 clinical trial for dry AMD - geographic atrophy.

Platelet-Derived Growth Factor Inhibitors: A Potential Therapeutic Approach for Ocular Neovascularization

Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factors (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF play an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly neovascular AMD, has become more exciting due to agents like PDGF antagonists.

High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera

Purpose To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus. Methods An adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors. Results Ten healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes. Conclusions The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.