Rubbia Afridi

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.

The Role of Optical Coherence Tomography Angiography in the Management of Uveitis.

Optical coherence tomography angiography (OCTA) is a novel technique for imaging blood vessels without the need for intravenous contrast administration. OCTA creates images of capillary networks by comparing the amount of light returned to a detector from static and moving targets on sequential scans. The mechanism of scan acquisition generally consists of a source light beam, which is split and directed to a reference mirror and the target tissue. Scanning of the target tissue yields a 3D cube of data, which is collected and translated by a camera and signal processor, respectively. A computer algorithm is then able to map the blood vessels given the relatively constant signal return of static tissue, and the fluctuant signal return of mobile tissue. Current software algorithms are termed OCT-based microangiography (OMAG). Thus, existing OCT hardware can be used to create micron-level resolution images of capillary networks within a 3 mm area of retina following a 3-second scan. As a highly active area of research, OCTA software and techniques have been refined rapidly in the last few years. Two FDA-approved

Sirolimus for Retinal and Uveitic Diseases

Chronic inflammation plays an important role in the pathogenesis of ocular diseases such as diabetic retinopathy, uveitis and age-related macular degeneration. Activation and proliferation of naïve T cells may result in pathological changes responsible for significant visual morbidity. Sirolimus (earlier termed rapamycin) is a novel drug that inhibits cellular kinases and, thereby, inhibits T-cell proliferation. Preclinical studies in experimental models have shown promising results with the use of this pharmacological agent in various ocular conditions. Subsequently, early phase I/II studies have provided encouraging safety and efficacy data. This chapter focuses on the mechanisms of action, preclinical study results and data from human clinical trials of sirolimus in human eye diseases. Key highlights from ongoing phase III clinical trials are also provided. Sirolimus, thus, appears to be an important addition to the armamentarium of steroid-sparing therapeutic agents that act on various steps in the inflammatory pathway.

Multimodal Imaging in Retinal Vasculitis

ABSTRACT Retinal vasculitis presents with inflammation involving the retinal vasculature as an isolated disease or in combination with other ocular or systemic conditions. This entity may be associated with a wide variety of clinical manifestations such as vascular sheathing, cotton-wool spots, retinal ischemia, and neovascularization. Often, retinal vasculitis and its complications lead to diagnostic challenges in identifying the exact etiology of the inflammation. Ancillary investigations such as fundus photography, fluorescein angiography, and more recently, adaptive optics imaging and optical coherence tomography angiography, may provide valuable information that help in establishing the exact diagnosis and initiation of appropriate therapy. In the index review, multimodal imaging features of retinal vasculitis are described. In addition, detection of vascular inflammation using novel noncontact imaging techniques has been highlighted.

The role of Aflibercept in the management of age-related macular degeneration.

ABSTRACT Introduction: During the past decade, significant advances have occurred in the management of neovascular age-related macular degeneration (NV-AMD). The advent of anti-vascular endothelial growth factor (anti-VEGF) therapy has shifted the treatment goal of NV-AMD from merely salvaging vision to improving visual acuity and maintaining a good quality of life. Aflibercept (AFL) is a significant addition to the arsenal of anti-VEGF therapies against the NV-AMD. In the index review, pharmacology and efficacy of AFL has been reviewed. Areas Covered: An extensive literature search was performed to identify preclinical and clinical studies performed to illustrate the role of AFL in NV-AMD. Randomized clinical trials evaluating other anti-VEGF agents were also included for comparison. Additionally, studies where AFL was employed to treat anti-VEGF-resistant cases agents have been reviewed. Expert Opinion: AFL is an effective agent in the management of NV-AMD and its efficacy has been found to be comparable to ranibizumab (RBZ). Additionally, AFL is a good alternative agent in patients with NV-AMD resistant to RBZ and bevacizumab (BVZ), and can potentially lessen the treatment burden. As more research is conducted, the role of AFL in varying dosing regimens, as monotherapy and in combination with other agents, will become further defined.

Fundus Autofluorescence Imaging in Posterior Uveitis

Fundus autofluorescence (FAF) is a relatively new but valuable imaging tool for multiple anatomical and physiological alterations in the ocular tissue secondary to inflammation, especially in posterior uveitis. FAF is the scale on which the health and function of the retinal pigment epithelium (RPE) can be measured. Essentially, FAF is a map of distribution of lipofuscin, which is the autofluorescent pigment of the eye, comprising of several types of fluorophores. Lipofuscin is naturally found in RPE due to photoreceptor outer segment turnover by RPE regularly. However, its excessive accumulation in the outer retina and neurosensory layer is observed in pathological processes.