Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part II: Retinal Toxicity of Current and New Drugs

Abstract

Aims: Retinal pharmacotherapy has gained great importance for the treatment of various retinal diseases. An increasing number of drugs have been constantly released into the market, especially for wet age-related macular disease and diabetic macular edema. In this review, the issues concerning the toxicity of current and new classes of drugs are discussed. Methods: An extensive search of the literature was performed to review various aspects of drug toxicity in retinal pharmacotherapy. The different major classes of drugs, such as corticosteroids, antibiotics, antimetabolites, antineoplastic agents, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs, enzymes, fibrinolytics, miscellaneous anti-inflammatory and antiangiogenic agents, as well as toxicity unrelated to the drug were identified and discussed. Results: Corticosteroids like fluocinolone, dexamethasone or triamcinolone at low dose cause little damage to the retina, but at high doses signs of toxicity have been well documented. Complications like cataract and glaucoma are quite common with corticosteroids. Aminoglycosides showed differences in the type and doses associated with toxic reactions, thereby the following order of toxicity can be described (from most toxic to least toxic): gentamicin > netilmicin = tobramycin > amikacin = kanamycin. Vancomycin at the usual dose of 1 mg is not toxic to the retina, while further studies are necessary in order to clarify the safety of new-generation quinolones. 5-Fluorouracil has been shown to be nontoxic to the retina after an injection of 2.5 mg in animals. mAbs like ranibizumab and bevacizumab were demonstrated to be safe to the retina in cell culture, animals and humans at high doses. The exact biocompatibility of nonsteroidal anti-inflammatory agents like diclofenac needs further evaluation. Preservatives like benzyl alcohol and changes in pH or osmolarity exert an influence on the toxic effects of intravitreally applied drugs. Conclusions: A great number of drugs are now used mainly intravitreally without relevant retinal toxicity.

Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

“…The clinical presentation of retinal edema with diffuse hemorrhages, vascular occlusion, sheathing, and capillary nonperfusion, similar to the cases herein presented, has been previously described with acute aminoglycoside toxicity [12]. One proposed mechanism for aminoglycoside toxicity is a vasoocclusive event, which has also been noted to occur more often after repetitive injection in non-vitrectomized eyes [12].…”

Treatment of refractory glaucoma with cystoid macular edema

“…Наконец, нельзя исключить негативное влия-ние 5-фторурацила на макулярную область, хотя субконъюнктивальные инъекции этого препарата в общепринятых дозах не сопровождаются рети-нотоксическими эффектами [4,13,16,17].…”

A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)

“…46,47 Nonetheless, interactions for AEs, HRQoL, survival or costs could occur if the number of injections required in the discontinuous groups differs between drugs (e.g. due to differences in pharmacokinetic properties [48][49][50] ).…”

“…46,47 Nonetheless, interactions for AEs, HRQoL, survival or costs could occur if the number of injections required in the discontinuous groups differs between drugs (e.g. due to differences in pharmacokinetic properties [48][49][50] ).However, the effect of treatment regimen will differ between drugs for anti-VEGF cost, as total drug cost equals cost per dose multiplied by number of doses. When drug costs are analysed on a natural scale, this produces a very large interaction for total costs and cost-effectiveness.…”