The adverse effects of drugs in the eye are not easily detected, and the underlying pathogenesis not fully understood. The effects of four different kinds of drugs have been investigated in the rabbit eye, using electroretinography, ocular examination and histochemical methods. Rifabutin is a broad spectrum antibiotic with known ocular adverse effects (corneal opacities, uveitis and vascular retinopathy) in the human eye. In the rabbit eye rifabutin causes lens discoloration and it significantly reduces both total rod-cone function and isolated cone function, but it does not affect retinal morphology. Ranibizumab, bevacizumab, and pegaptanib are inhibitors of the cytokine vascular endothelial growth factor. Pegaptanib and ranibizumab are approved for injection into the vitreous. Bevacizumab is a cancer drug injected off-label intravitreally. In rabbit rod-mediated function was found depressed 8 weeks after a single injection of all three VEGF inhibitors. Rod bipolar cells were affected in the groups injected with pegaptanib and ranibizumab, but not with bevacizumab. Triamcinolone acetonide is a corticosteroid with depot properties, used for intramuscular and intraarticular injections. In Europe, triamcinolone is commercially available only in combination with the preservative benzyl alcohol, and is not approved for intraocular use. Triamcinolone has been and is extensively used off-label for injections into the vitreous body. Intravitreal injection of triamcinolone and benzyl alcohol, separately and in combination, affected both retinal function and histology. Adalimumab, a monoclonal antibody against the pro-inflammatory cytokine tumor necrosis factor α is approved for subcutaneous injection in autoimmune diseases. The level of TNFα is raised in ocular inflammatory conditions. No functional disturbances were found on examination with ffERG after injection into the vitreous body of rabbits. Retinal histology was found to be intact. These studies have shown that drugs may affect both retinal function and histology in the rabbit eye, and that retinal electrophysiology combined with histochemistry can detect the retinal level and the cell type involved in these processes, or exclude retinal damage by the drug. This knowledge should alert ophthalmologists to perform extensive investigations in patients on medication who present with unaccountable visual symptoms.
Ophthalmology, Drug toxicity, electroretinography, histopathology, intravitreal injection, rifabutin, anti-VEGF, triamcinolone, benzyl alcohol, anti-TNF-alpha, adalimumab
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