The effects of cidofovir 1% with and without cyclosporin a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study.
OBJECTIVE
To evaluate the efficacy of cidofovir 1% eyedrops with and without cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis (AKC).


METHODS
Randomized, controlled trial.


METHODS
Thirty-four patients with acute adenoviral keratoconjunctivitis of recent onset.


METHODS
Patients were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir 10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily, and 4) sodium chloride four times daily (control). The diagnosis was confirmed by adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days.


METHODS
Severity of conjunctival injection, conjunctival chemosis, punctate epithelial keratitis during the course of treatment, and presence and severity of corneal subepithelial infiltrates were evaluated by a clinical score. Duration until subjective improvement of symptoms was recorded.


RESULTS
The frequency of severe corneal opacities was lower with cidofovir (P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were clinically similar to the signs of the initial viral inflammation. They first appeared 8 to 12 days after beginning of treatment and completely subsided 7 to 28 days after discontinuation of cidofovir. The outcome measures of local inflammation did not differ between the four treatment groups. Cyclosporin A did not alter the course of the infection.


CONCLUSIONS
Cidofovir lowers the frequency of severe corneal opacities, but its clinical use 4 to 10 times daily at a 1% concentration is limited by local toxicity. Further clinical studies to find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an improved pharmaceutical preparation, are required.
Hillenkamp
Jost
J
The Eye Hospital, Heinrich-Heine-University, Düsseldorf, Germany. hillenka@hotmail.com
Reinhard
Thomas
T
Ross
Rudolf S
RS
Böhringer
Daniel
D
Cartsburg
Olaf
O
Roggendorf
Michael
M
De Clercq
Erik
E
Godehardt
Erhard
E
Sundmacher
Rainer
R
D000208:Acute Disease; D000258:Adenovirus Infections, Human / Q000188:drug therapy* / Q000821:virology; D000260:Adenoviruses, Human / Q000235:genetics / Q000302:isolation & purification*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077404:Cidofovir; D003228:Conjunctiva / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D015828:Eye Infections, Viral / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D005143:Eyelids / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007637:Keratoconjunctivitis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012449:Safety
D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D016572:Cyclosporine; D003596:Cytosine; D000077404:Cidofovir