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      Combination Therapies in Ophthalmology: Implications for Intravitreal Delivery

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          Abstract

          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.

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          Most cited references65

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          Drug/device combinations for local drug therapies and infection prophylaxis.

          Peng Wu, David Grainger (2006)
          Combination devices-those comprising drug releasing components together with functional prosthetic implants-represent a versatile, emerging clinical technology promising to provide functional improvements to implant devices in several classes. Landmark antimicrobial catheters and the drug-eluting stent have heralded the entrance, and significantly, routes to FDA approval, for these devices into clinical practice. This review describes recent strategies creating implantable combination devices. Most prominent are new combination devices representing current orthopedic and cardiovascular implants with new added capabilities from on-board or directly associated drug delivery systems are now under development. Wound coverings and implantable sensors will also benefit from this combination enhancement. Infection mitigation, a common problem with implantable devices, is a current primary focus. On-going progress in cell-based therapeutics, progenitor cell exploitation, growth factor delivery and advanced formulation strategies will provide a more general and versatile basis for advanced combination device strategies. These seek to improve tissue-device integration and functional tissue regeneration. Future combination devices might best be completely re-designed de novo to deliver multiple bioactive agents over several spatial and temporal scales to enhance prosthetic device function, instead of the current 'add-on' approach to existing implant device designs never originally intending to function in tandem with drug delivery systems.
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            Triple therapy for choroidal neovascularization due to age-related macular degeneration: verteporfin PDT, bevacizumab, and dexamethasone.

            Stephan Puls, Albert J. Augustin, Indre Offermann (2007)
            To evaluate the efficacy and safety of triple therapy with verteporfin photodynamic therapy (PDT), dexamethasone, and bevacizumab in choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). This prospective, noncomparative, interventional case series included 104 patients. Verteporfin PDT was administered with a reduced light dose (42 J/cm, accomplished by light delivery time of 70 seconds). Approximately 16 hours after PDT, dexamethasone (800 microg) and bevacizumab (1.5 mg) were injected intravitreally. Patients attended follow-up visits every 6 weeks, undergoing visual acuity and intraocular pressure measurement, slit-lamp and ophthalmoscopic examination, and optical coherence tomography (OCT). Fluorescein angiography was performed every 3 months or earlier if OCT showed significant edema. All 104 patients received one triple therapy cycle (5 patients received a second triple treatment due to remaining CNV activity). The triple therapy was complemented in 18 patients (17.3%) by an additional intravitreal injection of bevacizumab. The mean follow-up period was 40 weeks (range, 22-60 weeks). Mean increase in visual acuity was 1.8 lines (P < 0.01). Mean decrease in retinal thickness was 182 microm (P < 0.01). No serious adverse events have been observed. In most patients with CNV due to AMD, triple therapy results in significant and sustained visual acuity improvement after only one cycle of treatment. In addition, the therapy offers a good safety profile, potentially lower cost compared with therapies that must be administered more frequently, and convenience for patients.
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              Extended release of dexamethasone from silicone-hydrogel contact lenses containing vitamin E.

              Jinah Kim, Anuj Chauhan, Cheng Peng (2010)
              Ophthalmic drug delivery by contact lenses is expected to be more efficient due to continuous extended release of drug and increased residence time in the tear film. However, commercial contact lenses release ophthalmic drugs for a short period of about an hour and are thus not suitable for extended delivery use. Here we explore a novel approach of increasing the release duration of dexamethasone (DX) from commercial contact lenses by loading Vitamin E into the lenses. The Vitamin E was loaded into the lenses by soaking the lenses in Vitamin E-ethanol solution followed by ethanol removal through evaporation. The results show that with about 30% of Vitamin E loading in the contact lens, the DX release time can be increased to 7 to 9 days for ACUVUE(®) OASYS™, NIGHT&DAY™, and O(2)OPTIX™, which is a 9 to 16 fold increase compared to the DX release duration by pure contact lens without Vitamin E loading. The DX delivery by contact lens can be viewed as a one-dimensional transport by a flat thin film, and a mathematical model based on the drug diffusivity difference between Vitamin E and silicone hydrogel was also proposed to explain the DX release time increase by Vitamin E loaded contact lens. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Ophthalmic Vis Res
                Journal ID (publisher-id): JOVR
                Title: Journal of Ophthalmic & Vision Research
                Publisher: Ophthalmic Research Center
                ISSN (Print): 2008-2010
                ISSN (Electronic): 2008-322X
                Publication date (Print): January 2011
                Volume: 6
                Issue: 1
                Pages: 36-46
                Affiliations
                [1 ]University of Arizona, Phoenix, Arizona, USA
                [2 ]Tulane University, New Orleans, Louisiana, USA
                [3 ]InSite Vision Inc., Alameda, California, USA
                Author notes
                Correspondence to: Gholam A. Peyman, MD. Emeritus Professor of Ophthalmology, Tulane University, New Orleans, Louisiana, USA; Professor of Basic Medical Sciences, University of Arizona, 10650 W. Tropicana Circle, Sun City, Arizona 85351, USA; Tel: +1 602 242 4928, Fax: +1 602 249 4813; e-mail: gpeyman1@ 123456yahoo.com
                Article
                Publisher ID: jovr-6-1-036
                PMC ID: 3306066
                PubMed ID: 22454705
                SO-VID: 471ac830-83b1-4f34-8e87-4e72d405f7b0
                Copyright statement: Copyright @ 2011
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 13 November 2010
                Date accepted : 22 December 2010
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: combination therapy,intravitreal delivery,combined modality therapy
                Data availability:
                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: combination therapy, intravitreal delivery, combined modality therapy

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