Causal Management of Keratoconus: Controlling Inflammation

We read with interest the article by Shetty et al.¹ on keratoconous and inflammation. 

They rightly stated that atopy has been associated with the disease. However, although that association has been identified for several decades, multiple studies have shown conflicting results.² There is also a very important confounding factor when one is analyzing the relationship between ocular allergy and keratoconus: the mechanical trauma caused by eye rubbing. In 1961, Ridley³ related eye rubbing to keratoconus. Much later, at the end of the 20th century, Bawazeer et al.⁴ published their now classic study on the topic, which had the primary goal of determining if atopy was a risk factor for keratoconus. They showed in a case–control study that in the univariate analysis there was an association between keratoconus and atopy, as well as eye rubbing and family history of keratoconus. However, in the multivariate analysis, only eye rubbing was maintained as a significant predictor of keratoconus. The conclusion of the authors was that atopy might contribute to keratoconus but most probably via eye rubbing associated with the irritation of atopy.⁴ The possible role of eye rubbing has been also suggested by other authors. Weed et al.⁵ in the Dundee University Scottish Keratoconus study found that when using a visual analogue scale to describe eye rubbing history, a statistically significant difference was identified between patients with keratoconus and normal patients. The keratoconic patients rubbed their eyes more frequently. 

Recently Gordon-Shaag et al.⁶ in Israel found that asthma and eczema were not significantly associated with keratoconus, while on the other hand, eye rubbing was identified as a significant risk factor. McMonnies⁷ has suggested several mechanisms by which the eye rubbing could promote corneal ectasia, including large intraocular pressure spikes; and some recent findings by Balasubramanian et al.,⁸ also cited by Shetty et al.,¹ support effects of the rubbing at molecular level: Eye rubbing was found to increase the level of tear matrix metalloproteinase (MMP)-13, IL-6, and TNF-α in normal eyes and in keratoconus. 

Passing now to another point, the results that the authors obtained on the effect of topical cyclosporine in patients with keratoconus are very significant. They identified corneal epithelium as a source of MMP-9 and proinflammatory cytokines in keratoconus, and thus it became a specific target for therapeutic modulation. According to our view, this study marked a new direction in the management of the disease, which is in line with what has been gradually identified in recent decades: the inflammatory nature of corneal ectasia. Certainly further studies are required with more patients and longer follow-up, but we are seeing the dawn of a causal therapeutic approach to this complex condition.