The assessment of disease progression in keratoconus and corneal crosslinking in thin corneae

Sammanfattning: Keratoconus generally manifests in adolescents, and can progress leading to severely impaired vision. The risk of progression is inversely correlated to age; thus younger patients are at higher risk than older ones. Progressive keratoconus can be halted by corneal crosslinking (CXL). The general indication for CXL is progressive keratoconus, although children are commonly treated with CXL upon diagnosis. Tomography is used to assess progression, and the most commonly used system is the Pentacam HR. Measurements made on different visits are compared to determine whether the patient’s keratoconus has progressed, and they should be referred for CXL. However, there is no consensus on which parameters should be used, or the change in magnitude of these parameters that indicates progression. An increase in the curvature power of the steepest point on the anterior surface, Kmax, of 1.0 dioptres is commonly used for all patients. However, there is little evidence that this is appropriate. Furthermore, inconsistent results have been presented regarding the magnitude at which progression can be detected. Such studies are often based on determinations of the repeatability of measurements made on one occasion. However, the progression of keratoconus is evaluated from measurements made on different occasions, and it is reasonable to assume that measurements obtained on different days will be subject to greater variation due to the biomechanical instability of corneae affected by keratoconus. Also, it has been suggested in studies that the repeatability of measurements in subjects with more severe keratoconus have poorer repeatability. Another important aspect of keratoconus is that it is a thinning disorder. A minimum corneal thickness of 400 µm has been suggested for the safe performance of CXL. Thus, a significant proportion of keratoconus patients will be excluded from the standard CXL treatment protocol.Thus, in the first study we elucidated the association between measurement error and disease severity. In the second investigation we investigated the inter-day repeatability and in the third investigation we investigated the Belin ABCD Progression Display. In the fourth study we investigate a protocol in which sterile water was added during the crosslinking procedure to increase the corneal thickness. The results demonstrated that the measurement error is associated to the disease severity and that limits at which progression is defined should be defined by inter-day measurements. The results also suggest that the diagnosis of progressive keratoconus by the Belin ABCD Progression Display will lead to overdiagnosis of progression. Further, the results suggest that the addition of sterile water is effective in increasing the corneal thickness above the suggested safety limits. These results have important clinical implications. The results demonstrate that limits at which progression is defined should be stratified according to the severity of the disease. Patients with less advanced keratoconus will be underdiagnosed as progressive if commonly used parameters are not stratified according to disease severity. This could lead to delayed referral for CXL, resulting in an avoidable risk of deterioration in vision. Patients with more advanced keratoconus, on the other hand, would be overdiagnosed as progressive, which could lead to unnecessary CXL, thus subjecting the patient to discomfort and possible treatment-associated complications. This risk of overdiagnosis of progression is also relevant when using the Belin ABCD Progression Display. Further, The data suggest that such a simple measure as adding sterile water during corneal crosslinking could enhance the corneal thickness above safety limits.