Future Perspectives: Agents on the Horizon.

As demonstrated in the previous chapters of this textbook, retinal pharmacotherapeutics is a rapidly developing area. The enormous burden of disease in an aging population will hopefully be met by significant improvements in our understanding and treatment of disease processes such as age-related macular degeneration (AMD) and diabetic retinopathy. This chapter will provide perspectives on select anti-angiogenic drugs currently in development, as well as therapies directed against the complement cascade for the treatment of AMD, and an anti-inflammatory monoclonal antibody for the treatment of diabetic macular edema, among others, that have not been discussed elsewhere in this book. The mechanism of action of a number of drugs under discussion differs enough to have the potential to control neovascularization in several different ways, potentially allowing for more effective management of this process with fewer treatments.

Structural Characteristics of Retinal Layers Adjacent to Geographic Atrophy.

BACKGROUND AND OBJECTIVE: To compare the anatomy of different retinal layers adjacent to areas of geographic atrophy (GA) to those of eyes with no known ocular diseases. PATIENTS AND METHODS: Spectral-domain optical coherence tomography (SD-OCT) scans from eyes with GA were retrospectively reviewed. Two scans with no findings suggestive of GA changes on OCT were selected from immediately above and/or below the edge of the lesions. Thickness values of the retinal layers were calculated and compared to values obtained from normal subjects. RESULTS: Forty-four eyes (30 patients) were compared to 20 healthy eyes. Retinal pigment epithelium (RPE), inner nuclear layer (INL), and full retinal thickness (FRT) values were significantly lower in patients compared to healthy subjects. Thicknesses of all other layers were not significantly different. CONCLUSION: Clinically appearing, non-involved RPE and INL layers of eyes with GA demonstrate significant thinning compared to corresponding layers in eyes with no known ocular diseases.

Emerging therapies for noninfectious uveitis: what may be coming to the clinics.

Corticosteroids along with other immunomodulatory therapies remain as the mainstay of treatment tor all patients with noninfectious uveitis (NIU). However, the systemic side effects associated with the long-term use of these drugs has encouraged the development of new therapeutic agents in recent times. This review article discusses upcoming therapeutic agents and drug delivery systems that are currently being used to treat patients with NIU. These agents mediate their actions by blocking specific pathways involved in the inflammatory process. Agents discussed in this review include full or recombinant monoclonal antibodies against interleukins such as IL-17 (secukinumab), IL-l (gevokizumab), and IL-6 (tocilizumab and sarilumab), antibody fragments against inflammatory cytokines such as TNF- α (ESBA 105) and T-cell inhibitors such as fusion proteins (abatacept), and next generation calcineurin inhibitors (voclosporin). In addition, administration of immune modulatory therapies using methods such as iontophoresis (EGP-437) and intravitreal injection (sirolimus) for the treatment of NIU' uveitis has also been discussed.

Differential induction of apoptosis and necrosis in monocytes from patients with tuberculosis and healthy control subjects.

BACKGROUND: Mycobacterium tuberculosis and purified protein derivative (PPD) induce apoptosis in murine macrophages and apoptosis and necrosis in human monocytes and alveolar epithelial cells. Macrophages from bronchoalveolar lavages and granulomas from patients with tuberculosis (TB) present both types of cell death; however, the significance of the type of cell death in TB remains uncertain. METHODS: Monocytes from PPD-positive control subjects and from patients with TB were exposed to PPD or M. tuberculosis. Apoptosis, necrosis, and the percentage of tumor necrosis factor (TNF)-alpha -positive and interleukin (IL)-10-positive cells were determined cytofluorometrically. Levels of lactate dehydrogenase, TNF-alpha, and IL-10 were measured in culture supernatants. The role of TNF-alpha and IL-10 was tested by blockade experiments. RESULTS: PPD and M. tuberculosis induced apoptosis in monocytes from PPD-positive control subjects, whereas cells from patients with TB presented apoptosis and necrosis. Cells from PPD-positive control subjects produced mainly TNF-alpha, whereas cells from patients with TB produced mainly IL-10. Blockade experiments suggest that TNF-alpha and IL-10 regulate the type of cell death occurring in response to M. tuberculosis. CONCLUSIONS: Results suggest that apoptosis of monocytes exposed to mycobacteria may partly explain the protective immune response found in PPD-positive control subjects, whereas necrosis may be determinant of the bacterial dissemination and tissue damage that occur in patients with active TB.