Faculty Bibliography

PURPOSE: To summarize the literature addressing sustained and delayed elevation of intraocular pressure (IOP) in patients with neovascular age-related macular degeneration being treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. METHODS: Analysis of current literature evaluating sustained and delayed elevation of IOP in patients receiving intravitreal anti-VEGF therapy for neovascular age-related macular degeneration. RESULTS: Studies have demonstrated that patients undergoing treatment with intravitreal anti-VEGF agents may experience sustained and delayed elevation of IOP. The incidence of sustained elevation of IOP in patients with neovascular age-related macular degeneration varied from 3.45% to 11.6%, and few patients required surgical management to control IOP. Possible risk factors associated with sustained and delayed elevation of IOP include, but are not limited to, history of glaucoma, phakia, history of glucocorticoid use, and/or extended treatment duration. There are multiple theories explaining the pathogenesis of sustained elevation of IOP, including microparticle obstruction of the trabecular meshwork, intraocular inflammation, and transient elevation of IOP. CONCLUSION: Sustained and delayed elevation of IOP in patients undergoing treatment of neovascular age-related macular degeneration with intravitreal anti-VEGF agents is likely a multifactorial process. Further studies to prospectively investigate sustained elevation of IOP in large, randomized, controlled trials might lead to a better understanding of the long-term adverse events associated with intravitreal anti-VEGF therapy.

This is a summary of current and emerging pharmacologic therapies utilized in the treatment of diabetic retinopathy (DR). Current therapies, such as ranibizumab, bevacizumab, triamcinolone acetonide, and fluocinolone acetonide, inhibit angiogenesis and inflammation and may be used alone or in combination with laser treatment. Emerging therapies aim to reduce oxidative stress or inhibit other signal transduction pathways, including the protein kinase C cascade and aldose reductase pathway. Future therapies may target other molecules crucial to the pathogenesis of DR, including hepatocyte growth factors and matrix metalloproteinase 9. Finally, the emergence of novel mechanisms of medication delivery may also be on the horizon.

PURPOSE: To determine whether there is an association between response to intravitreal anti-vascular endothelial growth factor agents and genotype in patients with neovascular age-related macular degeneration. METHODS: Analysis of the current literature evaluating pharmacogenetics of treatment response in patients with neovascular age-related macular degeneration. RESULTS: Studies have demonstrated associations between various genotypes and response to intravitreal anti-vascular endothelial growth factor agents. Lower-risk genotypes of the CFH, ARMS2, HTRA1, and VEGF-A genes may be associated with improved visual outcomes. Additionally, frequency of injections may be associated with certain genotypes. CONCLUSION: Genetic background may influence an individual's response to treatment of neovascular age-related macular degeneration. Further studies to investigate biologic pathways of neovascular age-related macular degeneration and gene products that are directly involved might lead to better understanding of contribution of various genes to treatment response.

BACKGROUND: This review summarizes the Phase III studies addressing intravitreal ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD), macular edema (ME) from retinal vein occlusion (RVO), and diabetic ME (DME). RESULTS: The data from 12 major Phase III studies: six studies in patients with neovascular AMD, two studies in patients with ME from RVO, and four studies in patients with DME demonstrate significant improvement in vision in patients undergoing treatment with intravitreal ranibizumab over patients receiving no treatment or receiving only grid laser. These effects are achieved with low incidences of ocular and nonocular adverse events. CONCLUSION: Intravitreal ranibizumab is a highly effective and safe therapy for improving vision and reducing vision loss in patients with neovascular AMD, ME from RVO, and DME. Patients generally require long-term treatment although some data show that frequency of treatment necessary to maintain visual outcomes decreases over time.