RESUMEN
PURPOSE: To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira®) in the rabbit eye. METHODS: Thirty New Zealand albino rabbits received intravitreous injections of 0.5 mg (6 eyes), 1.0 mg (6 eyes), 2.5 mg (6 eyes), 5 mg (6 eyes), and 10 mg (6 eyes) adalimumab. Slit lamp biomicroscopy and fundoscopy were carried out at baseline, day 7, and day 14 after intravitreous injection, whereas electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed. RESULTS: Slit lamp biomicroscopy and fundoscopy were normal in all eyes receiving doses up to 5 mg. In the 10 mg group, 3 of 6 eyes showed mild anterior chamber inflammatory reaction on day 7. Similarly, scotopic and photopic a- and b-wave ERG amplitudes at baseline and day 14 were similar in all groups up to 5 mg, but there was a significant decrease in the photopic-wave ERG response in the 10 mg group (P=0.046). Finally, histopathology demonstrated no differences among eyes receiving balanced salt solution, 0.5, 1.0, 2.5, 5.0, or 10 mg of adalimumab. CONCLUSIONS: Intravitreous adalimumab exhibited no associated ocular short-term toxicity in rabbit eyes up to the 5 mg dose. In the 10 mg group mild clinical findings and ERG amplitude reduction could reflect early toxicity.
Asunto(s)
Cámara Anterior/efectos de los fármacos , Antiinflamatorios/toxicidad , Anticuerpos Monoclonales Humanizados/toxicidad , Inflamación/inducido químicamente , Adalimumab , Animales , Cámara Anterior/patología , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Relación Dosis-Respuesta a Droga , Electrorretinografía/métodos , Femenino , Inyecciones Intravítreas , Microscopía/métodos , Oftalmoscopía/métodos , Conejos , Factores de TiempoRESUMEN
PURPOSE: To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira) in the rabbit eye. METHODS: Twelve New Zealand albino rabbits received unilateral intravitreous injections of 0.1 ml of adalimumab 0.25 mg (three eyes), 0.50 mg (three eyes), 1.0 mg (three eyes) or 0.1 ml balanced salt solution (BSS, three eyes). Slit-lamp biomicroscopy and fundoscopy were carried out at baseline, day 1, 7 and 14 following intravitreous injection, while electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed. RESULTS: Slit-lamp biomicroscopy and fundoscopy were normal in eyes having received BSS, 0.25 mg or 0.50 mg adalimumab; however, inflammation was present in two of three eyes having received 1.0 mg adalimumab. Similarly, comparison of scotopic and photopic ERG light at baseline and day 14 demonstrated no changes in eyes receiving BSS, 0.25 mg or 0.50 mg adalimumab, but two of three eyes having received 1.0 mg adalimumab showed a greater than 30% reduction in a and b wave. Finally, histopathology demonstrated no differences between eyes receiving BSS, 0.25 mg or 0.50 mg of adalimumab, but two of three eyes injected with 1.0 mg demonstrated inflammatory cell infiltration of the vitreous and anterior chamber, with one of these eyes demonstrating retinal necrosis. CONCLUSIONS: Escalating doses of intravitreous adalimumab in rabbit eyes caused no detectable functional or structural ocular toxicity up to a dose of 0.50 mg. Administration of 1.0 mg in 0.1 ml was associated with an inflammatory reaction and retinal necrosis.