Corneal ectasias: study cohorts and epidemiology.

Primary corneal ectasias such as classic keratoconus with inferior ectasia, central keratoconus, and butterfly (or claw)-shaped pellucid marginal corneal degenerations are likely genetically determined.1 Currently there is a lack of understanding of the genetic mechanisms due to limited data on this topic and treatment options in the past have been palliative and somewhat unsatisfactory.23

However, over the past 2 decades, improved diagnostics and a greater choice of staged treatment options compared to only contact lenses and penetrating keratoplasty have emerged.4 The diagnostic focus has shifted from the anterior cornea to the posterior cornea and the treatment options feature more targeted approaches including biological modifiers of the diseased tissue and lamellar surgical procedures. Data on ethnic differences in incidence and severity have attracted increased attention as the reported populations may harbor index patients for successful gene linkage studies.1

From the genetic standpoint, corneal ectasias are frequently lumped together as keratoconus, but it may represent a heterogeneous entity.5 Significant differences in the rate of progression, changes of specific topographic parameters including front and back elevation, deterioration of uncorrected visual acuity, central corneal thickness, elasticity, and other ocular parameters warrant a precise clinical identification and distinction in order to arrive at the diagnosis of central keratoconus, classic inferior keratoconus, or pellucid marginal corneal degeneration. A clear definition will facilitate the selection of appropriate cohorts for clinical trials. Currently, only few genetic marker studies are available. At this time, 3900 PubMed listed publications on keratoconus are available, of which only 300 are on genetics of keratoconus. However, future multiethnic population studies should include a phenotypic assessment including a differentiation between (what we now call) pellucid marginal corneal degeneration and KC, which would provide a clearer clinical understanding.6

Sustainable recommendations for treatment options can only be derived from genetically and phenotypically/clinically well-defined cohorts. Historically, the focus of “keratoconus” literature has been on the surgery of late-stage or end-stage manifestation, which may camouflage a noncoherent mix of conditions.

Population studies in the Middle East have reported a high (20:100000) incidence of keratoconus in secluded areas of Saudi Arabia,7 and similar data have been reported from a non-Arab, Iranian cohort at 22–25:100000.8 Penetrating keratoplasty data from Riyadh, Saudi Arabia reflect the findings of the aforementioned epidemiological study from Saudi Arabia.9

A study of Levante Arab cohort of students in Lebanon reported prevalence of keratoconus at 3.3%, with forme fruste keratoconus at 1.1%.10 A study from Jerusalem reports a similar incidence of 3.34% between Israeli Jews and Israeli Arabs.11 The incidence of corneal ectasia in the Middle East seems fairly comparable to that in certain Asian-Pacific populations at 22–25:100000 and differ significantly with Caucasian European and United States populations at 1.3–3:100000.12–15 A phenotype study in the Middle East has shown that butterfly-shaped pellucid marginal corneal degeneration with late progression is more frequent in Levante Arabs than in the Middle Eastern Arabs, whereas keratoconus with fast progression is more frequent in the Middle Eastern Arabs. The central keratoconus index was reported to be high in pellucid marginal corneal degeneration, and it appeared abnormal later than in keratoconus patients. The index of surface variation in pellucid marginal corneal degeneration was higher than in keratoconus patients at first presentation (Bialasiewicz AA WOC 2012 – submitted for publication).

Genetic studies rely on precise clinical information for a genotype-phenotype correlation. Although general multiethnic data represent an important step to find cohorts in whom gene identification may be more successful, clinical investigators should not bypass the fact that detailed phenotyping clearly adds value to a diagnosis, which is intrinsically important for correct treatment indications and genetic and proteomic studies. Such studies as mentioned above are yet to be performed in the Middle East and elsewhere as phenotypes may differ in Western and Asian populations.