Amiodarone keratopathy: an in vivo confocal microscopy study.
OBJECTIVE
To evaluate the characteristics and evolution of corneal morphologic changes induced by systemic amiodarone treatment by using in vivo slit scanning confocal microscopy in an attempt to understand the pathogenesis of corneal and other systemic side effects of this drug.


METHODS
Forty-nine eyes of 25 consecutive subjects receiving amiodarone therapy (group A) and 26 eyes of 13 age- and sex-matched healthy control subjects (group B) were enrolled in the study.


RESULTS
In group A, the mean dosage of amiodarone was 224.0 +/- 71.3 mg, and the mean duration of treatment was 21.3 +/- 20.9 months. In eight (8 of 49,16.3) eyes of four patients, no deposition was observed, neither by slitlamp nor by confocal microscopy. The deposition could be detected as early as 2 months after the onset of treatment in 41 (41 of 49, 83.7%) eyes, by slitlamp and confocal microscopy. Deposition was significantly correlated with the duration of treatment and, therefore, the cumulative dose of the drug ingested. Deposits were observed as bright, hyper-reflective spots that were localized intracellularly and were present at the level of basal lamina of all 41 (100%) corneas in which deposition could be observed at confocal microscopy. Deposits were also observed in the superficial epithelium, anterior stroma, mid stroma, and subepithelial nerves in eyes with grade 2 to 4 keratopathy. Additionally, morphologic abnormalities were observed in anterior stromal keratocytes, subepithelial and stromal nerves, and endothelium. The mean anterior and posterior keratocyte densities were statistically significantly higher than those in group B.


CONCLUSIONS
In addition to showing drug deposition does not seem to occur before 2 months of treatment and does not seem to be correlated with tear function. Although the clinical significance of morphologic changes induced by the drug is known and although deposition could not be detected before it was evident with slitlamp biomicroscopy, with some improvement in instrumentation, the authors believe that confocal microscopy will also prove to be useful in early diagnosis and in understanding the pathophysiology of amiodarone keratopathy. This may help grow insight to the mechanism of other, sometimes lethal, systemic side effects of this drug.
Uçakhan
Omür O
OO
Department of Ophthalmology, Ankara University School of Medicine, Ankara, Turkey. omuru@yahoo.com
Kanpolat
Ayfer
A
Ylmaz
Nurgül
N
Ozkan
Muhip
M
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000009:adverse effects* / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D016022:Case-Control Studies; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003316:Corneal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D014018:Tissue Distribution
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone