Improvement of corneal fluorescein staining in post cataract surgery of diabetic patients by an oral aldose reductase inhibitor, ONO-2235.
OBJECTIVE
While the mechanism in the pathogenesis of diabetic corneal disease is unclear, aldose reductase has been implicated in corneal disease. The effects of an oral aldose reductase inhibitor (ARI) on the ocular surface of diabetic patients after cataract surgery were studied.


METHODS
This clinical trial was designed to be randomised, double blinded, and placebo controlled. Pseudophakic patients with diabetes were randomly assigned to treatment with either oral ARI (ONO-2235) (n=12) or placebo (n=9) for 12 weeks. The vital staining of the ocular surface, tear production and clearance, break up time in tears (BUT), corneal and conjunctival sensation, and symptom score before treatments were examined as well as 4, 8, 12 weeks after the administration. Specular microscopic evaluation was also performed.


RESULTS
After a 12 week period of oral ARI administration, fluorescein staining scores (from 2.04 (SD 1.12) to 1.46 (1.18); p=0.016), conjunctival sensation (from 1.15 (0.37) to 1.36 (0.31); p=0.0006), and symptom scores (from 5.38 (1.932) to 4.00 (2.07); p=0.0002) recovered significantly. Fluorescein staining of oral ARI administration also decreased compared with placebo (p=0.017). Rose bengal staining, tear clearance, and corneal sensation were improved although this increase was minor. Tear production, BUT, and specular microscopic evaluation of the corneal epithelium and endothelium did not demonstrate a significant change.


CONCLUSIONS
Oral ARI opposes the ocular surface changes caused by diabetes, by recovery of ocular surface sensitivity as demonstrated through an improvement in vital staining.
Fujishima
H
H
Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan. fujishima@tdc.ac.jp
Tsubota
K
K
D000284:Administration, Oral; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002387:Cataract Extraction; D003228:Conjunctiva / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019793:Fluorescein; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D011184:Postoperative Period; D012236:Rhodanine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D012395:Rose Bengal; D012677:Sensation; D013666:Tears / Q000378:metabolism; D053778:Thiazolidines
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D053778:Thiazolidines; D012395:Rose Bengal; C038131:epalrestat; D012236:Rhodanine; D000449:Aldehyde Reductase; D019793:Fluorescein