Combination Therapies in Ophthalmology: Implications for Intravitreal Delivery

Most pathological processes involve complex molecular pathways that can only be modified or blocked by a combination of medications. Combination therapy has become a common practice in medicine. In ophthalmology, this approach has been used effectively to treat bacterial, fungal, proliferative/neoplastic, and inflammatory eye diseases and vascular proliferation. Combination therapy also encompasses the synergistic effect of electromagnetic radiation and medications. However, combination therapy can augment inherent complications of individual interventions, therefore vigilance is required. Complications of combination therapy include potential incompatibility among compounds and tissue toxicity. Understanding these effects will assist the ophthalmologist in his decision to maximize the benefits of combination therapy while avoiding an unfavorable outcome

Evaluation Of A New Silicone-Methane Polymer Contact Lens

A new gas permeable contact lens is produced using a solid silicone core and a plasma polymer surface. This surface is hydrophilic and impermeable to macromolecules. The surface characteristics of this lens were compared with the surface characteristics of available silicone contact lenses. We found that in contrast to our lens, the silicone contact lenses lost their hydrophilic surface with time. In addition, they are permeable to lipid dyes, eg, Sudan red. © 1983 Arch Ophthalmol All rights reserved

Oscillatory Photodynamic Therapy for Choroidal Neovascularization and Central Serous Retinopathy; a Pilot Study

Purpose: To report the preliminary results of oscillatory photodynamic therapy (OPDT) for choroidal neovascularization (CNV) and central serous retinopathy (CSR). Methods: This study included 7 eyes of 6 patients with CSR (2 eyes), idiopathic CNV (2 eyes), CNV due to age-related macular degeneration (AMD) (2 eyes), and peripapillary CNV secondary to presumed ocular histoplasmosis syndrome (1 eye). Intravenous verteporfin (6 mg/m2 body surface area) was infused over 10 minutes followed by oscillating laser (wavelength 689 nm) covering slightly beyond the entire lesion. An Area Centralis lens was applied and laser was delivered (600 mW/cm2 fluence rate and 50 J/cm2 dose). Intravitreal bevacizumab and dexamethasone combination therapy was used with OPDT in 4 eyes with CNV; intravitreal dexamethasone and triamcinolone acetonide were injected in the other eye with CNV. Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography (OCT) were performed at baseline and after treatment. Results: After mean follow-up of 7.1±5.1 months, visual acuity improved from 0.87±0.69 logMAR (20/160) to 0.60±0.65 logMAR (20/80) (P = 0.027); central foveal thickness decreased from 322±62.1 to 240.7±34.8 microns as measured by OCT (P = 0.018). Fluorescein angiography and OCT demonstrated cessation of vascular leakage, and resolution of hemorrhage and subretinal fluid in all eyes. No adverse events or recurrence were noted. Conclusion: OPDT was effective in treating CNV lesions and CSR. OPDT may be an improvement on standard PDT due to reduced side effects, thermal damage and scarring

Endogenous Endophthalmitis: Etiology and Treatment

This chapter comprehensively covers all aspects of endogenous endophthalmitis from systemic infectious agents, with an emphasis on reported and newer etiologies to broaden the diagnostic and investigative acumen of treating ophthalmic providers. The discussion includes the etiology of metastatic endophthalmitis and diagnostic investigations, including polymerase chain reaction (PCR), for identification of bacterial and viral infections involving the eye in both immunosuppressed in non-immunosuppressed patients. Additionally, we present clinical and diagnostic findings of fungal infections, protozoal infections, and helminthic infections. Pediatric cases are also reported and etiologies described. We discuss both etiology and diagnostic challenges. Current therapeutic modalities and outcomes are reviewed. While no two cases of metastatic endophthalmitis are the same, some similarities may exist that allow us to generalize how to approach and treat this potentially sight- and life-threatening spectrum of diseases and find the underlying systemic cause

Toxicidade intravítrea da rapamicina em olhos de coelhos

PURPOSE: To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. METHODS: Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 µg, 50 µg, 200 µg, and 1000 µg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. RESULTS: ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 µg. Histological results showed no retinal toxicity in all groups. CONCLUSION: Although ERG changes were identified at dosages between 50-1000 µg, the histology of all groups up to 1000 µg did not show any discernable abnormalities.OBJETIVO: Avaliar a toxicidade da injeção intravítrea de diferentes doses de rapamicina para a retina de coelhos. Rapamicina é uma potente droga imunossupressora aprovada clinicamente para a prevenção da rejeição de transplantes de orgãos. MÉTODOS: Doze coelhos albinos da Nova Zelândia foram usados neste estudo. Foram divididos em quatro grupos. Quatro diferentes doses de rapamicina foram preparadas nas seguintes concentrações: 20 µg, 50 µg, 200 µg, 1000 µg. Foram realizadas injeções intravítreas de 0,1 ml de cada concentração em um olho de três coelhos e 0,1 ml de solução salina foi injetada no olho contralateral de cada coelho. Foram realizadas biomicroscopia e fundoscopia e observamos sinais de inflamação, infecção ou toxicidade durante duas semanas. Fizemos um ERG antes do tratamento e outro 14 dias depois da injeção intravítrea. Os animais foram sacrificados, fizemos a enucleação dos olhos e preparamos o tecido para a avaliação histológica. RESULTADOS: Os resultados do ERG e da histologia demonstraram diminuição da resposta escotópica, entretanto essa diminuiç&atildeão foi dose dependente. A histologia foi normal em todos os grupos. CONCLUSÃO: A injeção intravítrea de rapamicina levou a alterações eletrorretinográficas nos grupos de 50-1000 µg, entretanto a histologia foi normal em todos os grupos até 1000 µg

Micro- and nanoparticulates

Pharmacotherapeutics has begun to play an increasingly important role in the management of patients with neovascular age-related macular degeneration (AMD). Because micro- and nano-particulates are currently being evaluated as a potential drug-delivery option for AMD patients, the purpose of this analysis was to describe how micro- and nano-particulates have been used experimentally and what their potential clinical applications may be. Micro- and nano-particulates have been used primarily on a pre-clinical basis as new drug-delivery devices in experimental models of neovascular AMD. It is likely that micro- and nano-particulates will become an important component of targeted clinical pharmacotherapeutics in patients with neovascular AMD