Hideki Miyake

Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.

PURPOSE A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD). METHODS Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks. Development of MGD was assessed by histopathology at 4-week intervals. The lid margin was observed by slit-lamp examination. After cessation of the HR-AD diet, the mice were fed a normal diet to restore normal eye conditions. Expression of cytokeratin 6 was determined by immunostaining. We evaluated the effects of topically applied azithromycin on the plugged orifice in this model. RESULTS After mice were fed the HR-AD diet, histopathology analysis showed hyperkeratinization of the ductal epithelium in the meibomian gland. Ductal hyperkeratinization resulted in the loss of acini, followed by atrophy of the gland. Slit-lamp examination revealed a markedly plugged orifice, telangiectasia, and a toothpaste-like meibum compared with that of a normal eyelid. Cessation of feeding with HR-AD ameliorated both the MGD signs and the expression of cytokeratin 6, restoring the tissue to a histologically normal state. Azithromycin treatment significantly decreased the number of plugged orifices and ameliorated atrophy, as revealed by histopathologic analysis. CONCLUSIONS We developed a novel model that mimics human MGD signs in HR-1 hairless mice fed an HR-AD diet. Azithromycin treatment led to therapeutic improvement in this model. This MGD model could be useful for the evaluation of drug candidates for MGD.

Tear volume estimation using a modified Schirmer test: a randomized, multicenter, double-blind trial comparing 3% diquafosol ophthalmic solution and artificial tears in dry eye patients

Purpose We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients. Patients and methods A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests. Results According to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears. Conclusion The modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear-secreting compounds for dry eye.

A Novel Model of Meibomian Gland Dysfunction Induced with Complete Freund’s Adjuvant in Rabbits

A novel meibomian gland dysfunction (MGD) model induced by the injection of complete Freund’s adjuvant (CFA) in rabbits was developed to facilitate the understanding of the pathophysiology of MGD with meibomitis. In addition, we sought to evaluate treatment with steroid eye drops in this model. Male Japanese white rabbits were subcutaneously injected with CFA into the upper eyelid margin. The eyelid margins of the rabbits were chronologically observed through slit lamp examination. The development of meibomitis was assessed through histopathology. We evaluated the effects of topically applied tobramycin/dexamethasone (Tob/Dex) eye drops on the plugged orifices and telangiectasia. After the injection of CFA, slit lamp examination revealed markedly plugged orifices, telangiectasia around the orifices and a toothpaste-like meibum, as compared with the normal eyelids. Histopathology revealed granulation tissue with infiltration of inflammatory cells, hyperkeratinization of the ductal epithelium, and cystic dilatation of ducts in the meibomian gland. The orifices were plugged with a proteinaceous substance. Tob/Dex eye drops significantly suppressed the plugging and telangiectasia around the orifices. Through the injection of CFA, we successfully established a novel rabbit MGD that mimics the symptoms observed in humans meibomitis. This model should be useful in the evaluation of the efficacy of drug candidates.