Evolving multidimensional pharmacological approaches to CNV therapy in AMD.

PURPOSE: The leading cause of severe visual loss world-wide is age-related macular degeneration. Although anti-Vascular Endothelial Growth Factor agents have significantly led to the initial pharmacologic reversal of vision loss in many cases of exudative macular degeneration, there still has been recurrence of choroidal neovascularization, and/or the onset of chorioretinal atrophy with fibrosis. MATERIALS AND METHODS: In this review we discuss the status of anti- Vascular Endothelial Growth Factor in age-related macular degeneration and describe different studies focused on new potential therapeutic targets beyond anti- Vascular Endothelial Growth Factor. RESULTS: Further investigations have elicited that Vascular Endothelial Growth Factor is only one of many angiogenic, and pro-inflammatory factors that bring about the growth and leakage of active choroidal neovascularization. Various new multifaceted strategies, including inhibitors to down-stream targets of endothelial cell division, such as TNP-470, may lead to a more permanent inactivation of choroidal neovascularization. CONCLUSIONS: Based on the accumulated results in the treatment of age-related macular degeneration, it is hoped that the appropriate combination of anti-Vascular Endothelial Growth Factor agents with longer-acting and multidimensional pharmaceuticals, such as Methionine Aminopeptidase-2 inhibitors, will more effectively control choroidal neovascularization, prevent atrophy and fibrosis, and reduce the burden of frequent intraocular injections in age-related macular degeneration.

Murine fundus fluorescein angiography: An alternative approach using a handheld camera.

In today's modern pharmacologic approach to treating sight-threatening retinal vascular disorders, there is an increasing demand for a compact, mobile, lightweight and cost-effective fluorescein fundus camera to document the effects of antiangiogenic drugs on laser-induced choroidal neovascularization (CNV) in mice and other experimental animals. We have adapted the use of the Kowa Genesis Df Camera to perform Fundus Fluorescein Angiography (FFA) in mice. The 1 kg, 28 cm high camera has built-in barrier and exciter filters to allow digital FFA recording to a Compact Flash memory card. Furthermore, this handheld unit has a steady Indirect Lens Holder that firmly attaches to the main unit, that securely holds a 90 diopter lens in position, in order to facilitate appropriate focus and stability, for photographing the delicate central murine fundus. This easily portable fundus fluorescein camera can effectively record exceptional central retinal vascular detail in murine laser-induced CNV, while readily allowing the investigator to adjust the camera's position according to the variable head and eye movements that can randomly occur while the mouse is optimally anesthetized. This movable image recording device, with efficiencies of space, time, cost, energy and personnel, has enabled us to accurately document the alterations in the central choroidal and retinal vasculature following induction of CNV, implemented by argon-green laser photocoagulation and disruption of Bruch's Membrane, in the experimental murine model of exudative macular degeneration.

Combining Sodium Hyaluronate and Polyvinylpyrrolidone Therapies for the Rabbit Cornea: A New Approach to Relief of the Human Dry Eye Syndrome.

PURPOSE OF THE STUDY: The novel combination of 0.1% sodium hyaluronate (HA) and 5.0% polyvinylpyrrolidone (PVP) into one eyedrop was investigated to test the hypothesis of its increased relief of dry eye syndrome (DES). MATERIALS AND METHODS: We evaluated HA and PVP, either alone, or in combination, by utilizing 16 rabbits, where their right eyes received one or two different eyedrops, and their left eyes, as controls, received none. The DES replica in rabbits was induced by 0.1% benzalkonium chloride (BAC) eyedrops. BAC was instilled into the right eyes of all rabbits, which were divided into four groups of four. In Group 1 M, the rabbits received only BAC. A second eyedrop given to the right eyes of Group 2 M was HA, of Group 3 M was PVP, and of Group 4 M was the combination of both HA and PVP. All eyes were followed clinically for 14 d, and thereafter, examined histopathologically. RESULTS: Clinically, the HA+PVP combination yielded the least perilimbal conjunctival erythema (p < 0.05), and the least corneal epithelial fluorescein staining (p < 0.001) compared to each treatment alone. Histopathologically, all four rabbits' right eyes in the combination group 4 M displayed the greatest preservation of the corneal epithelium (p < 0.001) and of the perilimbal conjunctival goblet cell density (p < 0.001). CONCLUSIONS: This unique combination of both HA and PVP into one eyedrop, was more potent than either treatment alone in protecting the ocular surface. A preparation, containing both HA and PVP may become useful for DES patients.