1. Vitrasert Ganciclovir Intraocular Implant Reservoir style implant used for the delivery of the anti-viral prodrug ganciclovir. Vitrasert was the first non-biodegradable, intravitreal implant approved by the FDA in 1996 for the treatment of AIDs-related Cytomegalovirus (CMV) Retinitis which is estimated to affect between 15-40% of AIDS patients. 14 CMV Retinitis is a chronic, sight-threatening, infection of the retina caused by the cytomegalovirus (DNA virus of the herpes group), which predominantly affects immunosuppressed individuals and can lead to vision loss and blindness. Ganciclovir is a synthetic analogue of the nucleoside 2-deoxyguanosine, which causes chain termination, preventing replication. Each implant holds 4.5-5mg of the drug which is released at a slow constant rate of approx. 1-1.5µg/hr over 5-8 months. The 4mm device consists of a compressed drug pellet core is completely covered, except at its top surface, with the impermeable polymer ethylene vinyl acetate (EVA).This entire assembly is then coated by the permeable polymer, polyvinoyl alcohol (PVA) which regulates the drug’s diffusion. Water enters into the device dissolving the pellet and creating a saturated environment resulting in the sustained diffusion of the drug to the site of infection. The implant is surgically inserted into the posterior segment of the eye by making a 5-6mm scleral incision into the pars plana which is part of the ciliary body. It is then fixed into place using sutures. The wound is closed and a saline solution is injected to restore normal ocular pressure. The surgery typically takes an hour and is carried out under local anaesthetic. Surgery is necessary to remove the device once depleted of the drug and a new implant is then inserted. Most patients experience blurred vision which usually clears between 2-4 weeks after surgery. Though uncommon, complications include; endohpthalmitis, retinal detachment, cataract formation and vitreous haemorrhage. The Vitrasert implant only targets the localized site in the eye. However, CMV is a systemic disease which can affect other parts of the body, and thus the patient must be monitored closely for the development of non-ocular CMV and given intravenous ganciclovir if the infection has spread. Before implantation was possible the drug had to be injected intravitreally once to twice a week due to the short half-life of the drug. This caused poor patient compliance and increased the risk of the drug’s side effects. Advantages in comparison to I.V. ganciclovir include; reduced dosing frequency, enhanced drug efficacy, and reduced risk of toxicity. Phase III trial results from Bausch & Lomb of 188 AIDS patients with recently diagnosed CMV Retinitis showed that treatment with Vitrasert implant, significantly delayed the time to disease progression compared to treatment with intravenous ganciclovir. The mean time to disease progression was approx. 122 days for patients who received the implant in comparison to 72 days for the I.V. Ganciclovir group.

2. References 1.http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=18322http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=18322 2.http://www.rxlist.com/vitrasert-drug.htmhttp://www.rxlist.com/vitrasert-drug.htm 3.http://www.sciencedirect.com.eproxy.ucd.ie/science/article/pii/S0169409X06001645http://www.sciencedirect.com.eproxy.ucd.ie/science/article/pii/S0169409X06001645 4.http://emedicine.medscape.com/article/1227228-overview#a0104http://emedicine.medscape.com/article/1227228-overview#a0104 5.http://www.retinatoday.com/Html%20Pages/0307/0307_feature_kuppermann.pdfhttp://www.retinatoday.com/Html%20Pages/0307/0307_feature_kuppermann.pdf 6.http://www.iovs.org/content/45/8/2722.full.pdfhttp://www.iovs.org/content/45/8/2722.full.pdf 7.https://mail- attachment.googleusercontent.com/attachment/?ui=2&ik=f37170b2bc&view=att&th=13586d2d 5c3f686a&attid=0.1&disp=inline&realattid=f_gypyhscd0&safe=1&zwhttps://mail- attachment.googleusercontent.com/attachment/?ui=2&ik=f37170b2bc&view=att&th=13586d2d 5c3f686a&attid=0.1&disp=inline&realattid=f_gypyhscd0&safe=1&zw 8.http://bjo.bmj.com/content/82/3/332.3.fullhttp://bjo.bmj.com/content/82/3/332.3.full 9.http://bjo.bmj.com/content/83/11/1225.fullhttp://bjo.bmj.com/content/83/11/1225.full 10.http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v3/v3c028a.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v3/v3c028a.html 11.http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c045.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c045.html 12.http://www.medicinenet.com/ganciclovir-intravitreal_implant/article.hthttp://www.medicinenet.com/ganciclovir-intravitreal_implant/article.ht 13.http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=18322http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=18322 14. Henderly DE, Freeman WR, Causey DM et al: Cytomegalovirus retinitis and response to therapy with ganciclovir. Ophthalmology 94:425, 1987