Ocular toxicity of intravitreal trovafloxacin in the pigmented rabbit.
OBJECTIVE
Trovafloxacin is an expanded spectrum, newer-generation fluoroquinolone antibiotic with improved Gram-positive and anaerobic activity compared with existing quinolones, while maintaining Gram-negative activity comparable to ciprofloxacin. Given its broad spectrum of activity, trovafloxacin may have potential use for treatment of acute bacterial endophthalmitis. This study examined the toxicity of intravitreally administered trovafloxacin in the pigmented rabbit eye.


METHODS
Doses of trovafloxacin ranging from 12.5 microg to 1000 microg were injected into the mid-vitreous of Dutch Belted rabbit eyes. Clinical examination was performed at 1, 3, and 14 days following injection. Animals were sacrificed and eyes were enucleated 14 days following injection. Light microscopy (LM) and transmission electron microscopy (TEM) studies of the optic nerve head, medullary ray, and inferior retina were performed to determine toxicity.


RESULTS
At intravitreal doses of 500 microg and less, no toxicity was observed at the ophthalmoscopic or light microscopic level. By TEM, a dose-dependent increase in injury to retinal pigment epithelium, photoreceptors, and nerve fibers in the optic nerve head and medullary ray was observed from 50 microg to 500 microg. No toxicity was noted at doses of 12.5 microg and 25 microg. At doses of 750 microg and above, edema of the medullary ray was noted on ophthalmoscopy. Swelling of the peripapillary medullary ray and necrosis of the inferior retina were evident on LM.


CONCLUSIONS
Intravitreal trovafloxacin doses of 50 microg and higher in the pigmented rabbit eye cause retinal and nerve fiber injury. Intravitreal doses 25 microg and lower appear to be safe, with no evidence of ocular toxicity.
Ng
Eugene W M
EW
Ocular Microbiology Laboratory, The Wilmer Ophthalmological Institute, Baltimore, MD 21287-9121, USA.
Joo
Myung-Jin
MJ
Au Eong
Kah-Guan
KG
Green
W Richard
WR
O'Brien
Terrence P
TP
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000633:toxicity*; D007267:Injections; D008297:Male; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009887:Ophthalmoscopy; D009898:Optic Disk / Q000187:drug effects* / Q000648:ultrastructure; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000648:ultrastructure; D014822:Vitreous Body / Q000187:drug effects*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin