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Abstract B ecause of the long delay in bringing drug to the vitreoretinal compartment from systemic or subconjunctival injection, direct injection into the vitreal cavity is required and in some diseases when the wellbeing of the retina is threatened, it is the only acceptable method. Although an intravitreal injection is a safe procedure, it is not completely devoid of risk. These risks can include vitreous hemorrhage, retinal tear, and retinal detachment, as well as endophthtalmitis. The possible danger of this procedure has limited its use to conditions in which the eye is at high risk for considerable visual loss. These might include endophthalmitis, proliferative vitreoretinopathy, tumors, and severe inflammation. The danger of injection may be somewhat overstated; it is probably safe when administerated carefully. Repeated injections are frequentaly required, and they are not always well tolerated by the patient. Since multiple intravitreal injections are traumatic to the patient, it is clear that means must be developed to sustain drug concentration in the vitreous cavity while minimizing its toxicity and enhancing its efficacy. These novel systems are called vitrasert. There are a number of intravitreal medications that can be toxic to the eye. While the adverse effects of many of these are reversible upon drug cessation if detected early enough. Retinal physicians must employ their clinical acumen, as well as a host of imaging technologies including fluorescein angiography (FA), optical coherence tomography (OCT), ultrasonography, perimetry, electroretinography (ERG), to detect the earliest signs of retinal and uveal drug toxicity. Numerous pharmacologic agents have been tested and used for intravitreal drug therapy: Anti vascular endothelial growth factor.Vascular Endothelial Growth Factor (VEGF) plays a large role in the development of wet age-related macular degeneration (AMD) and other retinal vascular diseases. Multiple new treatments that block VEGF are now clinically available such as Pegaptanib, Bevacizumab, Ranibizumab,and VEGF-Trap. However, VEGF is a survival factor for the developing and mature retina (a survival factor for endothelial and neural cells). In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability. Thus, inhibiting VEGF could lead to geographic atrophy and poor visual acuity. A low rate (<4%) of arterial thromboembolic events was observed with ranibizumab injection. Corticosteroids are used for both posterior and severe anterior segment inflammatory diseases. These drugs include Dexamthasone and Triamcinolone which are used in the treatment of intraocular proliferative, oedematous, and neovascular diseases, and other clinical conditions. They are commonly safe intravitreal drugs. However, intraocular pressure (IOP) elevation may occur in up to 50 % of eyes after Triamcinolone injection. Other potential risks include cataract development, retinal detachment, endophthalmitis, pseudoendophthalmitis and pseudohypopyon plus injection-related complications. Antibacterial drug therapy such as, Vancomycin, Ciprofloxacin, Ceftriaxone, Clindamycin, Clarithroicin, Amikacin, Ceftazidime, and Gentamicin are used in the treatment of endophthalmits. The most accepted combination is Vancomycin with Amikacin or Ceftazidime. Amikacin is more preferable for its proved efficacy but Ceftazidime is safer as Amikacin is reported to cause retinal haemorrhage and discrete areas of capillary non-perfusion. Because of the low therapeutic index of aminoglycosides even relatively small dilution errors can cause retinal toxicity. Antiviral drugs such as Ganciclovir, Foscarnit and Cidofovir are used in the treatment of cytomegalovirus retinitis. They are effective in controlling CMV retinitis but may be associated with ocular complications, including retinal detachment, endophthalmitis, and a significant rate of relapse of CMV retinitis. Antifungal drugs such as. Amphotericin B, Fluconazole, Voriconazole, Cilofungin and Miconazole are used in the treatment of fungal endophthalmitis. The most commonly used and effective drug is Amphotericin B but it is considerably highly toxic as when injected into rabbit eyes at various concentrations of 1 0, 20, 30, 40 and 50 µg doses, ophthalmoscopic examination showed vitreous opacity and band formation, so Voriconazole could be used. Antiproliferative drugs such as Fluorouracil, Daunorubicin, Doxorubicin and Aclacinomycin A. Fluorouracil is the most safe drug. Antineoplastic agents such as, Methotrexate which is effective. But on twice weekly injections, filamentary keratitis was noted in few patients. Other observed complications included transient conjunctivitis, mild vitreous hemorrhage, and cataract formation. No retinal detachment has so far been induced. Ocular recurrences have been observed in three patients. These responded well to reinstitution of the intravitreal injections of Methotrexate. Fibrinolytic agents such as, TPA and Tenecteplase which are used in the treatment of vitreous haemorrhage, premacular and subretinal haemorrhage, and CRVO. At doses of 75, 100, and 200 µg of intravitreal TPA, the eye shows mild to moderate anterior chamber inflammation with inflammatory vitreous debris. Eyes injected with 200µg of TPA developed a more severe vitreitis. Drugs that act on cell attachment by blocking the attachment of cells to fibrin and collagen such as, Heparin, LMWH and Hirudin. They are used to decrease postoperative fibrin formation and PVR but increase intraoperative bleeding (Antithrombin). Drugs inhibiting cell migration and contraction such as Colchicine and Taxol can be used in the treatment of PVR. They are not used due to their toxic effects on the retina also they cause optic atrophy. Morphologic changes including progressive swelling of retinal neurons, accumulation of a fibrinogranular material, and inflammatory cell infilteration may also ocur. Miscellaneous drugs such as Mitomycin-C, Indocyanine Green (lCG), Trypan blue, Vitamin A, and Vitamin E. Intravitreal injection of 0.4 mg/ml of Mitomycin-C showed selective degeneration of Muller cell process at day 2, RPE changes at day 4 and irregular arrangement of the outer nuclear layer and photoreceptors at day 7. On intravitreal administration of lCG, the ILM was detached. Ultrastructural analysis showed cellular swelling and disruption of Muller cell processes. Vitreous substitute including Silicone oil that may lead to impregnation and reproliferation of epiretinal membranes, and Perfluorocarbon liquids that may exert mechanical effects on cell function by impeding the normal metabolic exchange between the endothelium and the medium. |