Aclacinomycin A in the treatment of experimental proliferative vitreoretinopathy. Efficacy and toxicity in the rabbit eye.
OBJECTIVE
Aclacinomycin A is an oligosaccharide anthracycline that, by contrast with daunomycin, lacks carcinogenicity. The authors evaluated the efficacy of aclacinomycin A in prevention of experimental proliferative vitreoretinopathy (PVR) and its toxicity on the rabbit retina.


METHODS
Dutch-belted rabbit were used to create a model for traction retinal detachment. Seven to 10 days after vitreous gas compression, 25,000 homologous fibroblasts were injected into the vitreous cavity. Subsequently, the eyes received either sham injections or doses of 6, 30, or 60 nmol of aclacinomycin A, respectively. The fundus findings were documented on days 7, 14, and 28 after the fibroblast injection. The toxicity studies were conducted according to the same protocol as was used for the efficacy evaluation but without the fibroblast injection. Simultaneous electroretinograms were recorded on days 0, 3, 7, and 14 from the right eyes that were injected with 30 or 60 nmol of aclacinomycin A and the left eyes that were sham injected. Morphologic studies were conducted on the eyes enucleated on days 3, 7, and 14 after drug exposure.


RESULTS
Intraocular administration of 30 nmol of aclacinomycin A on day 2 after fibroblast injection resulted in a detachment rate of 37.5% (controls, 100%; P < 0.01, by Fisher's exact test). Administration of 60 nmol of aclacinomycin A 3 days after fibroblast injection resulted in a detachment rate of 26.7% (controls, 100%; P < 0.0001). Six nanomoles of aclacinomycin A 3 days after fibroblast injection had no effect. No electroretinogram changes were present in eyes treated with 30 nmol of aclacinomycin A. Such recordings from eyes exposed to 60 nmol of aclacinomycin A demonstrated decreased a- and b-waves on day 3; these completely recovered by day 7. Morphologic studies of these eyes revealed no damage to the retina.


CONCLUSIONS
These results suggest that aclacinomycin A should be considered an alternative to daunomycin for treatment of human PVR because, in addition to its lack of carcinogenicity, it shows good efficacy and causes less retinal toxicity.
Steinhorst
U H
UH
Department of Ophthalmology, Duke University, Durham, North Carolina.
Chen
E P
EP
Hatchell
D L
DL
Samsa
G P
GP
Saloupis
P T
PT
Westendorf
J
J
Machemer
R
R
D015250:Aclarubicin / Q000627:therapeutic use* / Q000633:toxicity*; D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D005128:Eye Diseases / Q000473:pathology / Q000517:prevention & control; D005260:Female; D005347:Fibroblasts; D005500:Follow-Up Studies; D005654:Fundus Oculi; D008297:Male; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000648:ultrastructure; D012163:Retinal Detachment / Q000517:prevention & control; D012164:Retinal Diseases / Q000473:pathology / Q000517:prevention & control*; D014822:Vitreous Body / Q000187:drug effects* / Q000473:pathology
D015250:Aclarubicin