Understanding keratoconus: what have we learned from the New Zealand perspective?

Abstract

Although first described more than 150 years ago, keratoconus is still an enigmatic disease that remains an area of wide-ranging, dynamic, international research. This review considers data from New Zealand/Aotearoa, where keratoconus is both relatively common and extensively studied. New Zealand researchers have made several significant contributions to the international literature in this field, including identifying a higher prevalence of keratoconus in New Zealand per se and within Maori and Polynesian populations compared to many international studies. As reported in other studies, a higher proportion of asthma, allergy and eczema as potential risk co-factors are present in New Zealand subjects with keratoconus compared with estimates from the general population. The rates of family history of keratoconus are typically higher than those reported internationally, with higher rates in Asian, Pacific and Maori ethnicities. Interestingly, such a positive family history has been associated with less severe keratoconus on computerised topographic analysis. Investigations of corneal microstructure have revealed dramatic alterations in the keratoconic cornea, with reduced density and abnormal morphology of the corneal sub-basal nerve plexus and decreased keratocytic density. Laboratory studies of keratoconic corneal buttons have also furthered our understanding of the pathophysiology of this disease, demonstrating elevated levels of cathepsin enzymes and localised disruptions in Bowman's layer with incursion of cellular processes from anterior keratocytes. Over the past two decades keratoconus has consistently remained the leading indication for corneal transplantation in New Zealand, accounting for over 40 per cent of cases. Indeed, New Zealand appears to have the highest reported proportion of transplantation surgery for keratoconus worldwide. Current and future studies of keratoconus in New Zealand highlight an emphasis on elucidating the genetics of, and investigating novel therapeutic interventions for, this relatively common corneal disease.

Inflammation and Keratoconus

“…31 Significantly lower keratocyte densities have been found in subjects with KC in comparison with age-matched control subjects. 33 In particular, the reduction in density of keratocytes was significant in the anterior stroma of keratoconic subjects with contact lens wear and in the posterior stroma of all keratoconic subjects (with or without contact lens wear). 33 There may be a common set of epithelial cellkeratocyte interactions in KC that are mediated by growth factors, chemokines, cytokines, and neural peptides.…”

“…33 In particular, the reduction in density of keratocytes was significant in the anterior stroma of keratoconic subjects with contact lens wear and in the posterior stroma of all keratoconic subjects (with or without contact lens wear). 33 There may be a common set of epithelial cellkeratocyte interactions in KC that are mediated by growth factors, chemokines, cytokines, and neural peptides. 34 There are several potential sources of cytokine release within the cornea and anterior chamber.…”

Epigenetic Mechanisms Might Help Explain Environmental Contributions to the Pathogenesis of Keratoconus

“…2 Several mechanisms for corneal weakening and/or thinning in KC have been described. 4 The etiology of KC is probably multifactorial, 5 representing the final common pathway for a variety of different pathological processes 6 involving both genetic and environmental processes. 4 The etiology of KC is probably multifactorial, 5 representing the final common pathway for a variety of different pathological processes 6 involving both genetic and environmental processes.…”

“…3 Nevertheless, despite intensive research activity over the years into the etiology and pathogenesis of KC since 1984, KC still remains an enigmatic disease in inheritance, prevention, associated risk factors, disease progression, treatment, and underlying pathophysiology. 1,[4][5][6] In some patients, unilateral KC has been found to only develop in the eye that is subjected to frequent episodes of abnormal levels of rubbing trauma. 1,[4][5][6] In some patients, unilateral KC has been found to only develop in the eye that is subjected to frequent episodes of abnormal levels of rubbing trauma.…”

Ultrasound biomicroscopy as a diagnostic method of corneal degeneration and inflammation

“…Major advances in the treatment of KC include improved technology in rigid gas permeable and hybrid contact lenses and corneal transplantation (72,73,(92)(93)(94). PKP offers good longterm visual rehabilitation for KC (79,(94)(95)(96)(97)(98).…”