Purpose:
To explore a new 12 clock-hour grading of Grade 4 lesions and computer-aided image analysis of late phase fluorescein angiograms from retinal lesions of experimental laser-induced CNV in cynomolgus monkeys.
Methods:
40 cynomolgus (20M/20F) monkeys with 6 treatment groups and two dose routes (Intravitreous: saline control, bevacizumab, adalimumab and ESBA105; Topical: saline control and ESBA105) were included in the study. Laser induction of CNV and subsequent FA grading on post-laser days 15, 22 and 29 was performed according to the traditional method of Krzystolik MG et al (Arch Ophthalmol 2002). The total number of clock hours (each clock hour subtending an angle of 30 degrees) of late FA that extended beyond the borders of the treated area was estimated visually and recorded for each Grade 4 lesion. A third (quantitative) method of grading late phase FA for each eye used Image J software (NIH) to determine both total and Grade 4 cumulative leakage area and relative mean intensity of Grade 4 cumulative leakage area.
Results:
Compared to the traditional Grade 4 grading method, subdividing Grade 4 lesions into a 12 clock-hour grading gave much greater differences and the best differentiation among the intravitreous treatment groups (a 6- and 14-fold difference between ESBA 105 and adalimumab to saline control treatments, respectively). Relative intensity determinations and the traditional Grade 4 grading method showed comparable sensitivity to each other (1.9- and 2.5-fold differences, respectively, when comparing adalimumab to saline control treatments).
Conclusions:
Results suggest the new 12 clock-hour grading method may be a more sensitive alternative to the traditional grading method, providing an effective means to differentiate the efficacy of various treatments. The results further suggest relative intensity analysis is comparable to the traditional Grade 4 grading, providing a convenient means of evaluation with less dependency on human expertise.
Keywords: age-related macular degeneration • choroid: neovascularization • imaging/image analysis: non-clinical