New Therapies for ARMD 1 Thursday 17 May 14:30 - 16:00 Salle Camille Blanc
R.R. Buggage, For The Macugen Primate Study Group,
USA
Electroretinographic parameters in monkey eyes are altered following intravitreal injections of bevacizumab but are unchanged by pegaptanib
PURPOSE: Preclinical studies have provided evidence that VEGF plays a neuroprotective role in conditions of retinal ischemia suggesting that long-term blockade of all isoforms of VEGF may threaten retinal neuronal survival. Accordingly, we employed electroretinographic measurements to study the effect of intravitreal pegaptanib and bevacizumab on retinal function in monkeys. SETTING: This was a preclinical study conducted at the Duke University Eye Center, Durham, North Carolina in United States. METHODS: Monkeys received bilateral intravitreal injections of either Bevacizumab 1.25 mg (n=6) or pegaptanib 0.3 mg (n=6) on days 1,22 (week 4), 43 (week 7), and 64 (week 10) of the study, and were sacrificed at week 14. Electroretinographic measurements were made at baseline and during weeks 5, 8, 11, and 14, and included (i) a full field scotopic and photopic electroretinogram (ERG); (ii) a multifocal ERG; (iii) a pattern-reversal (checkerboard) ERG (PERG); and (iv) a pattern-reversal visual evoked potential (VEP). RESULTS: The animals had similar baseline characteristics. None of the ERG parameters measured were affected by pegaptanib. In contrast, bevacizumab treatment led to a reduction from baseline in the post-dose scotopic b-wave of the full-field ERG reflecting altered rod-driven retinal function. This effect was observed in all animals, with both right and left eyes responding similarly, and occurred across a wide range of flash intensities and was evident at all test points. While there were isolated PERG effects in both eyes of 2 bevacizumab-treated animals, there were no changes from baseline in the cone-driven photopic ERG, multifocal ERG, or cortical VEP. CONCLUSIONS: In monkeys, intravitreal Pegaptanib administration appears not to affect retinal function, as assessed by electroretinographic measurements. In contrast, intravitreal injections of bevacizumab led to changes in both full-field ERG and PERG measurements. These findings suggest that inactivation of all VEGF isoforms may impair the health of retinal photoreceptors. FINANCIAL DISCLOSURE: Research supported by (OSI) Eyetech, Inc. and Pfizer Inc.
