Table 1 In-life and histopathological assessments of toxicity following single intravitreal injection of felodipine in rabbits.

Group		Vehicle		Felodipine (7.8 nmol/eye)		Felodipine (78 nmol/eye)		Felodipine (780 nmol/eye)
Animals (eyes)		3 animals (6 eyes)		3 animals (6 eyes)		3 animals (6 eyes)		3 animals (6 eyes)
Clinical signs		-		-		1 to 6 h ^a): Lacrimation 1/3, right eye		-
Body weight		-		-		-		-
Slit lamp examination	Eye	Right	Left	Right	Left	Right	Left	Right	Left
	Day 1–4 h ^a)	-	-	-	PCO⁑1/3	Floater# 3/3	Floater# 1/3	TA 3/3	TA 3/3
	Day 2	-	-	-	PCO⁑1/3	-	-	TA 2/3	TA 3/3
	Day 7	-	-	-	PCO⁑1/3	-	-	TA 3/3	TA 3/3
Fundus examination	Day 1–4 h ^a)	-	-	-	-	-	-	-	-
	Day 2	-	-	-	-	-	-	-	-
	Day 7	-	-	-	-	-	-	-	-
Histopathology	Granuloma/injection site ^b)	0/1^c)		0/3 ^c)		0/1 ^c)		±: 1/1^c)

TA: Test article; PCO: Posterior capsular opacity. ±: Very slight, -: No specific findings. #Diffused drug particles ⁑: caused by intravitreal injection procedure. (a) Time after intravitreal injection; (b) foreign body reaction; (c) number of findings of granuloma/injection site on the eyeballs in which the location of the administration needle puncture could be seen on the section slide. The lacrimation was unrelated to the drug. The floaters were not toxic because they appeared to be aggregated drug particles that diffused from a depot of the injected test article during the in-life examination. Granuloma at the injection sites was a foreign body reaction but was not considered to be drug-related toxicity.

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