Treatment of herpes retinitis in an animal model with a sustained delivery antiviral drug, liposomal 1-O-octadecyl-SN-glycerol-3-phosphonoformate.
OBJECTIVE
To evaluate the clinical treatment efficacy of a long-lasting intravitreous injectable anti-cytomegalovirus (CMV) liposomal drug, 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA).


METHODS
Sixty-four pigmented rabbits were used for evaluation of the potency and duration of action of ODG-PFA after intravitreal injection using a herpes simplex virus (HSV)-1 retinitis model. For the potency evaluation, liposomal ODG-PFA was injected into rabbit vitreous at the same time that HSV-1 virus was inoculated onto the retina (simultaneous treatment). For the duration evaluation, ODG-PFA was injected days or weeks before inoculation (pretreatment). Retinitis was clinically graded by indirect ophthalmoscopy, and the retinitis scores were compared across the treatment and control groups.


RESULTS
Simultaneous treatment study revealed that ODG-PFA was much more potent than its parent compound, foscarnet (P = 0.0027). Pretreatment study indicated that ODG-PFA possesses a much longer antiviral effect (at least 2 weeks) than foscarnet after a single intravitreal injection.


CONCLUSIONS
Liposomal ODG-PFA is a potent long-lasting intravitreal injectable antiviral compound that may be an ideal alternative for treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.
Cheng
L
L
Shiley Eye Center, University of California-San Diego, La Jolla 92093-0946, USA.
Hostetler
K Y
KY
Chaidhawangul
S
S
Gardner
M F
MF
Ozerdem
U
U
Bergeron-Lynn
G
G
Mach-Hofacre
B
B
Mueller
A J
AJ
Severson
G M
GM
Freeman
W R
WR
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D015828:Eye Infections, Viral / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D005500:Follow-Up Studies; D017245:Foscarnet / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000472:pathogenicity; D008081:Liposomes; D010742:Phospholipid Ethers / Q000008:administration & dosage*; D011817:Rabbits; D012160:Retina / Q000473:pathology / Q000821:virology; D012173:Retinitis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D016896:Treatment Outcome
C119381:1-O-octadecyl-sn-glycerol-3-phosphonoformate; D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D010742:Phospholipid Ethers; D017245:Foscarnet