Keratoconus: the arc of past, present and future

It is almost 160 years since Nottingham (1854) published his landmark treatise that defined keratoconus in the contemporary sense; however, in this issue Gryzbowski and McGhee highlight that much earlier descriptions of the disease were briefly recorded by Duddell (1736) and in more detail by John ‘Chevalier’ Taylor (1766). Importantly, in the 19 century other works, not equally feted, preceded Nottingham’s description in delineating keratoconus in considered detail. Such early reports often contain surprisingly prescient clinical descriptions, although the understanding of the disease process was generally limited. So, as we consider this 2013 special edition of Clinical and Experimental Optometry, dedicated entirely to keratoconus, perhaps we should contemplate how approaching three centuries of knowledge has increased our understanding of keratoconus and yet in many respects, it still remains the perplexing and challenging disease entity reported by Pickford. Through the revolution in molecular genetics the inheritance of many corneal dystrophies has now been delineated to a single nucleotide polymorphism. In contrast, while many syndromes and systemic conditions have been associated with keratoconus (for example, Down, Marfan, Ehlers-Danlos, mitral valve prolapse), the genetics of keratoconus remain far from completely understood. Burdon and Vincent and Edwards et al provide an incisive, review of contemporary genetic analyses, while highlighting that keratoconus has both genetic and environmental components. Indeed, despite extensive search over many years for a common genetic predisposition, none has yet been established, although candidates include VSX1, SOD1, ZEB1, TGFBI and collagen genes. Keratoconus is of particular regional relevance in Australasia, since it has long been established as the most common indication for corneal transplantation in both Australia and New Zealand. Thus keratoconus has become a strong focus of clinical and research interest in Australasia leading to a multitude of publications in the last two decades from diverse, established research groups. In this edition, Patel and McGhee highlight the inter-relationship of such clinical and laboratory research in New Zealand, while elsewhere, others cover the gamut of keratoconus studies from aetiology to treatment options. Keratoconus is typically described as a non-inflammatory, corneal ectasia; however, Cheung et al expand on the theory that keratoconus is due, at least in part, to altered wound healing and propose that repair and oxidative pathways in the cornea are linked. This new perspective may lead to the contention that pro-inflammatory events are involved in the keratoconus disease process. Eye rubbing as a source of repetitive micro-trauma in keratoconus has long been postulated. This concept has been particularly championed by Charles McMonnies, who reviews the potential effect of altered IOP on corneal ectasias; noting that body position, playing wind instruments and eye rubbing, in particular, may elevate IOP from modest levels to transient peaks of up to 400 mmHg. In an era, wherein we are increasingly aware of the effects of environmental factors in making manifest the underlying genetic predisposition to keratoconus, this association provides a potential area for intervention via patient education and therapeutic strategies to reduce ocular itch and eye rubbing. Interestingly, in a related experimental study of normal subjects, Balasubramanian et al record that eye rubbing for 60 seconds increases the level of tear MMP-13, IL-6 and TNF-alpha, which may predispose to tissue degradation in the context of keratoconus. In the UK and Australasia, keratoconus is typically diagnosed by the optometrist and three studies in this edition examine aspects of clinical presentation and management of keratoconus. In a population with a high prevalence of keratoconus, Shneor et al studied 244 patients presenting to optometric services in Israel and identified a number of features common to UK and Australasian studies including: 1. male preponderance 2. the majority (79 per cent) corrected by contact lenses 3. corneal transplantation in more than 20 per cent 4. high prevalence of eye rubbing (66 per cent) and 5. moderate family history of keratoconus (28 per cent). In juxtaposition, a study by Fan et al of acute corneal hydrops from New Zealand highlights associations between ethnicity and hydrops and a surprisingly late presentation to optometry/ophthalmology (with 31 per cent of subjects never having attended an eye care professional prior to hydrops). The corneal thinning, steepening and irregularity that are intrinsic to keratoconus make accurate measurement of intra-ocular pressure (IOP) by Goldmann tonometry both difficult and unreliable. Interestingly, C L I N I C A L A N D E X P E R I M E N T A L