Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit |
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Authors: | Roberta P A Manzano Gholam A Peyman Petros E Carvounis Muhamet Kivilcim Palwasha Khan Patricia Chevez-Barrios Walter Takahashi |
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Institution: | 1.Department of Ophthalmology,University of S?o Paulo,S?o Paulo,Brazil;2.Department of Ophthalmology,University of Arizona,Tucson,USA;3.Department of Ophthalmology,Baylor College of Medicine,Houston,USA;4.Department of Ophthalmology,Tulane School of Medicine,New Orleans,USA;5.Department of Pathology,The Methodist Hospital,Houston,USA |
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Abstract: | 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, threeeyes). 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.
None of the authors has any proprietary interest in any technique or product described herein.
The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology
to review their data. |
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Keywords: | Adalimumab Intravitreous injection Retinal toxicity Tissue necrosis factor-alpha (TNF-alpha) Macular edema Chronic uveitis |
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