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Intravitreal Administration of Antiviral Agents in Silicone Oil-Filled Human Eyes

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Intravitreal Administration of Antiviral Agents in Silicone Oil-Filled Human Eyes Intravitreal Administration of Antiviral Agents in Silicone OileFilled Human Eyes Amit Meshi, MD, Asaf Friehmann, MD, Sarah Sella, MD, Raz Gepstein, MD, Sharon Armarnik, MD, Ehud I. Assia, MD, Alexander Rubowitz, MD Purpose: To report our experience with intra-silicone oil (SO) injection of antiviral agents for treatment of viral retinitis and to review the relevant literature. Design: Two case reports and a literature review. Participants: Two patients with viral retinitis and SO tamponade. Methods: Two patients with viral retinitis were treated with intravitreal injections of low-dose ganciclovir (2 mg/0.05 ml), foscarnet (1.2 mg/0.05 ml), or both after retinal detachment repair with SO tamponade, in addition to systemic antiviral therapy from 2014 through 2015. The literature on the use of intraocular antiviral agents in the setting of SO vitreous substitute was reviewed. Main Outcome Measures: Clinical outcomes after administration of intra-SO antiviral therapy. Results: A patient with progressive outer retinal necrosis received 5 intra-SO injections of low-dose ganciclovir and foscarnet after surgery over 6 weeks. Another patient with acute retinal necrosis received weekly low-dose foscarnet injections into his SO-filled eye for 8 weeks after surgery. Significant retinitis regression with long-term retinitis control was achieved in both patients throughout follow-up. No articles reporting the administration of soluble antiviral agents into an SO-filled human eye were identified. Conclusions: Our preliminary findings indicate that administration of low-dose ganciclovir and foscarnet into an SO-filled eye may be used as adjunctive treatment for viral retinitis. Further studies are needed to confirm these results. Ophthalmology Retina 2017;-:1e6 ª 2016 by the American Academy of Ophthalmology Silicone oil (SO; polydimethylsiloxane) was introduced in administration.8 Intraocular therapy is an important method the early 1960s for treatment of retinal detachment (RD)1 of delivering antiviral medications. Reaching effective doses and since has become an invaluable aid to the retinal at the site of infection, avoiding systemic toxicity, achieving surgeon for managing complex surgical cases. Indications good local retinitis control, and delaying relapse are the for SO tamponade include, but are not limited to, complex main advantages of this method.8 Intravitreal ganciclovir, and traumatic RD, giant retinal tears, proliferative diabetic foscarnet, and cidofovir were shown to be safe and retinopathy, macular hole surgery, and endophthalmitis.2 effective adjunctive therapy for the management of Intravitreal administration of therapeutic agents for the patients with necrotizing herpetic and cytomegalovirus treatment of many vitreoretinal conditions, such as age- (CMV) retinitis.9e12 Rhegmatogenous RD is a common related macular degeneration, diabetic retinopathy, retinal complication of viral retinitis, especially in areas of thin and vascular diseases, uveitis, endophthalmitis, viral retinitis, atrophic retina,13 and many eyes require long-term SO and intraocular tumors, has become widespread in recent tamponade to maintain retinal reattachment.8 These patients years. Most injectable agents are water soluble and may still require intra-SO antiviral therapy because of reti- distribute evenly in the hydrophilic environment of the nitis. Ganciclovir was the only soluble antiviral agent vitreous humor. However, in the presence of SO tamponade, studied under SO in rabbit models, with inconclusive evi- the delivery and concentration of drugs injected into the dence regarding its safety.5,6 In immunocompromised pa- posterior segment of the eye become unpredictable.3 The tients, ganciclovir implant was shown to be safe and drug has to migrate through the oil and integrate gradually effective in controlling CMV retinitis with SO tamponade, into the vitreous fluid to reach the retina. This process and therefore has been advocated in such cases.14,15 We may affect its pharmacokinetic and pharmacodynamic report our experience with intravitreal antiviral administra- properties.4 A major concern in this situation is the tion in SO-filled eyes and review the current literature on the development of retinal toxicity resulting from high drug subject. concentrations in the thin film of fluid between the SO 5 and retina. Most information in the literature on the Methods administration of drugs into SO-filled eyes is derived from 4e7 rabbit models and has limited clinical application. Two patients with viral retinitis, one with progressive outer retinal Treatment of viral retinitis, a devastating ocular infection, necrosis (PORN) and another with acute retinal necrosis (ARN), often includes systemic and intraocular antiviral drug were treated at our ophthalmology department in 2014 and 2015. Ó 2016 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.oret.2016.12.006 1 Published by Elsevier Inc. ISSN 2468-6530/17 Ophthalmology Retina Volume -, Number -, Month 2017 Both patients required vitrectomy with SO tamponade because of weeks because of retinitis progression. This was followed by rhegmatogenous RD. They were given systemic and intravitreal maintenance with oral valacyclovir (1 g  3/day) and valganci- antiviral therapy, as recommended in the literature.8,11,16,17 clovir (450 mg  2/day). Bilateral intravitreal injections of fos- Systemic treatment for the patient with PORN included 5-week carnet (2.4 mg/0.1 ml) and ganciclovir (2 mg/0.05 ml) were induction with intravenous acyclovir (500 mg  3/day) and gan- administered twice weekly for induction. Highly active antiretro- ciclovir (250 mg  2/day). Intravenous foscarnet (4.5 g  2/day) viral therapy was initiated on the third week of hospitalization, as was added at week 3 for 2 weeks because of retinitis progression. advised by an infectious diseases consultant. This was followed by indefinite maintenance with oral valacyclovir Despite this treatment, retinal inflammation and necrosis (1 g  3/day) and valganciclovir (450 mg  2/day). Systemic continued to progress in both eyes. Within 2 weeks, BCVA dete- treatment for the patient with ARN included 2-week induction with riorated dramatically to 20/200 in the right eye and no light oral valacyclovir (2 g  3/day), followed by 4 months of valacy- perception in the left eye. In the right eye, lesions and hemorrhages clovir 1 g  3/day. This was changed to oral acyclovir 800 mg  5/ increased in number and size throughout the retina and a superior day for life-long maintenance. RD developed (Fig 2A). In the left eye, total exudative Adjunctive intravitreal antiviral therapy for PORN included 2- hemorrhagic RD with severe retinal necrosis and vascular week induction with foscarnet (2.4 mg/0.1 ml) and ganciclovir sclerosis developed (Fig 2B). Consequently, intravitreal treatment (2 mg/0.05 ml) injections twice weekly before the RD surgery. to the left eye was discontinued. After surgery, low-dose foscarnet (1.2 mg/0.05 ml) and ganciclovir Retinal detachment in the right eye progressed, despite attempts (2 mg/0.05 ml) were injected weekly into the SO-filled eye for to contain it with laser retinopexy. Pars plana vitrectomy (PPV) maintenance.18,19 The foscarnet dose was reduced by half to avoid with SO injection was performed during the third week of hospi- retinal toxicity and the ganciclovir dose was not changed because it talization. After surgery, low-dose intra-SO injections of foscarnet was less than the toxic threshold.6 Intraocular therapy in the patient (1.2 mg/0.05 ml) and ganciclovir (2 mg/0.05 ml) were given for with ARN was initiated only after the RD repair. It included retinitis control. Because the patient already had received a 2-week weekly intra-SO injections of low-dose foscarnet (1.2 mg/0.05 induction of biweekly intravitreal antiviral injections before sur- ml). The weekly injection interval was based on the foscarnet gery, a weekly interval was chosen for maintenance.18,19 The pa- treatment regimen for ARN with no SO tamponade.17 tient received 5 injections of each drug over a period of 6 weeks. PubMed, MEDLINE, EMBASE, and Web of Science databases Under this combined systemic and intraocular treatment, the were searched for articles published in English through August retinitis improved dramatically. The retinal lesions regressed and 2016 describing the use of intraocular antiviral agents in the setting the retina remained attached (Fig 3). The patient was discharged 8 of SO vitreous substitute. The search terms were viral retinitis, weeks after admission on a maintenance regimen of oral retinal detachment, silicone oil tamponade, and intravitreal ther- valacyclovir and valganciclovir, as described above. The BCVA apy. All studies and reports found were included. Relevant refer- in the right eye was 20/40 at that time. ences used in the studies also were evaluated. Three months after surgery, RD recurred with no evidence of active retinal lesions or hemorrhages. A second retinal reattach- ment surgery was performed with retinectomy, subretinal fluid Results drainage, and SO tamponade. One month after the second surgery, BCVA was 20/60. During the remaining 9-month follow-up, intra- Patient 1 SO injection of antiviral agents was not resumed because no reti- nitis was observed and the retina remained attached. A 38-year-old man with a history of chronic hepatitis B infection sought treatment at the emergency department for decreased vision in both eyes for several weeks, accompanied by red eyes and left Patient 2 eye pain
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