Cyclosporine in ocular surface inflammation

Abstract

Use in dry eye disease: influence on related corneal neuropathy?Dry eye disease (DED) is the most frequent encountered ocular surface condition and remains one of the world's most overlooked and treatment elusive ocular conditions. 1,2 There a multitude of lubricating eye drops, agents/approaches to deal with the condition and associated external eye disease. 3 Without gaining much in symptomatic relief.In 2007, the International Dry Eye WorkShop produced the DEWS report. 1,3,4 Over the past decade, this has made a significant impact rationalising the approach on the management of DED. For example, the DEWS report has been particularly helpful in dividing the classification of DED into Evaporative and Aqueous Deficient Dry Eye. 4 The report has also helped to focus on improving the tools for DED assessment and stimulated pharmaceutical firms to develop new therapies.We also know there have been many weaknesses of the original DEWS report and the International Working Group have recently reconvened and a revised version DEWS report, the DEWS II report is to be published soon. 5 From DEWS I, a strong role for inflammation in DED pathogenesis is described. 4 Chronic inflammation leads to structural changes to the corneal surface and anti-inflammatory agents like topical steroids in varying strengths can improve symptoms. If inflammation could be controlled over the long-term, we would expect more sustained benefits in symptom control. However, the use of steroids over longer periods is limited by the risks of intraocular pressure rise and/or cataract formation. 3 An alternative to long-term topical steroids is the use of topical cyclosporine. 6 Different formulations of this agent have been shown to improve features in DED with a lower risk profile than topical steroid. Topical cyclosporin can safely control chronic ocular surface inflammation over a long period. Such improved control offers the opportunity to evaluate the changes in corneal structure. 3 In this issue, Iaccheri et al 7 have used topical cyclosporine 0.05% twice a day for 6 months in patients with established dry eye disease (Sjögren's and Non-Sjögren's). The drug appeared to be well tolerated with o5% of patients discontinuing the medication. As expected, there were improvements in DED symptoms with ocular surface parameters such as improvements in OSDI questionnaire, tear break time and ocular surface staining.What appears more interesting are the structural changes found on corneal confocal microscopy over a 6-month period of therapy. They confirmed findings that corneal epithelial cell density substantially increased with lower 'keratocyte activation'. 8 But they show the number of sub-basal nerves were reduced by almost half with similar changes to nerve reflectivity and tortuosity. The results provide the strongest evidence so far for a correlation between the changes in nerve morphology and the degree of dry eye.Results from previous studies examining the changes to the subepithelial plexus have produced conflicting findings. Some showing dec...

Comparison of therapeutic effects between topical 8-oxo-2′-deoxyguanosine and corticosteroid in ocular alkali burn model

“…Currently, topical corticosteroids are reportedly the most potent anti-inflammatory agents available for treating ocular surface inflammation. Although T cell inhibitors such as cyclosporin A and tacrolimus, are effective against ocular surface inflammation, their anti-inflammatory effects are not as potent as those treated with corticosteroids, especially in acute exacerbation of ocular inflammation 1 , 2 . However, long-term use of topical corticosteroid is clinically restricted owing to potential risks such as secondary infection, elevated intraocular pressure, and cataract formation 3 .…”