Improving precision for detecting change in the shape of the cornea in patients with keratoconus

To investigate a method for precision analysis to discriminate true corneal change from measurement imprecision in keratoconus (KC). Thirty patients with KC and 30 healthy controls were included. Coefficients of repeatability and limits of agreement (LOA) were compared using multiple measurements for inter-observer and inter-device agreement with the Pentacam HR, Orbscan IIz, and Tomey Casia SS-1000. Correlation of repeated measurements was evaluated using a linear mixed effect model (also called random effect model). A formula was derived for the theoretical expected change in precision and compared with measured change. Correlation between measurements from the same eye was small (R = 0.13). The 99.73% LOA (3 SD) of the mean of three measurements, provided better precision than 95% LOA (2 SD) of single cut-off values as expected from statistical theory for uncorrelated measurements for evidence of a significant change in corneal shape in patients with keratoconus. This enabled the determination of cut-off values for the detection of true change in corneal shape. The mean of three repeated measurements will provide better precision when there is minimal correlation. Three (rather than two) standard deviations provides a precise estimate of the LOA within or between observers and can be used as a reliable measure for identifying stage-independent corneal shape changes (progression) in keratoconus

Learning physical examination skills outside timetabled training sessions: what happens and why?

Lack of published studies on students’ practice behaviour of physical examination skills outside timetabled training sessions inspired this study into what activities medical students undertake to improve their skills and factors influencing this. Six focus groups of a total of 52 students from Years 1–3 using a pre-established interview guide. Interviews were recorded, transcribed and analyzed using qualitative methods. The interview guide was based on questionnaire results; overall response rate for Years 1–3 was 90% (n = 875). Students report a variety of activities to improve their physical examination skills. On average, students devote 20% of self-study time to skill training with Year 1 students practising significantly more than Year 3 students. Practice patterns shift from just-in-time learning to a longitudinal selfdirected approach. Factors influencing this change are assessment methods and simulated/real patients. Learning resources used include textbooks, examination guidelines, scientific articles, the Internet, videos/DVDs and scoring forms from previous OSCEs. Practising skills on fellow students happens at university rooms or at home. Also family and friends were mentioned to help. Simulated/real patients stimulated students to practise of physical examination skills, initially causing confusion and anxiety about skill performance but leading to increased feelings of competence. Difficult or enjoyable skills stimulate students to practise. The strategies students adopt to master physical examination skills outside timetabled training sessions are self-directed. OSCE assessment does have influence, but learning takes place also when there is no upcoming assessment. Simulated and real patients provide strong incentives to work on skills. Early patient contacts make students feel more prepared for clinical practice

Keratoconus : Epidemiology, treatment effects and economic evaluation

Keratoconus is a disease of the cornea that usually has its onset during puberty or early adulthood. The annual incidence of keratoconus is 1 per 7500 and the estimated prevalence in the general population is 1 per 375. These values are five-fold to ten-fold higher than previously reported values in population studies. In advanced keratoconus cases a corneal transplantation is often warranted to restore visual function. Receiving a corneal transplant has a substantial impact on quality of life, especially when visual acuity deteriorates or if a corneal transplantation must be performed to restore visual acuity. Preventing the need for corneal transplantation is one of the priorities in keratoconus care. In the Netherlands, the annual number of corneal transplantations decreased after the introduction of corneal crosslinking, suggesting that crosslinking can reduce the need for corneal transplantation. Lamellar transplantation techniques were increasingly performed over the last decade, accounting for approximately 35% of keratoplasties in 2010 and thereafter. The classic penetrating keratoplasty is still common, with a stable frequency form 2010 onwards. This thesis provided evidence for the stabilizing effect of crosslinking in children up to five years. An interesting finding was that the chance of progression despite crosslinking treatment is much higher in children (22%) then in adults (2-10%). The prognosis after treatment is related to the location of the cornea that is most affected by keratoconus; patients with more central cones benefitting more from treatment in terms of cone flattening and patients with lower pre-treatment visual acuity are more likely to benefit from crosslinking with respect to visual acuity. Although the transepithelial crosslinking technique was initially lauded by many for its potential beneficial effects, head-to-head comparison between the transepithelial technique and the (original) epithelium-off technique demonstrated that transepithelial crosslinking was less effective in halting keratoconus progression than epithelium-off crosslinking. Furthermore, there was no clinically relevant difference between the two techniques on higher-order aberration, which are optical disturbances of the cornea that are not correctable by glasses and that are much more frequent in keratoconic eyes than in normal eyes. The cost of the crosslinking treatment, including pre-treatment screening and one year follow-up are €1759.06 ($1929.47). In order to investigate the rational of investing money in crosslinking treatments in order to prevent future corneal transplantations and loss of visual acuity, we performed a cost-effectiveness analysis. Cost-effectiveness turned out to be strongly influenced by the assumption of crosslinking effectiveness duration. The longest documented stabilizing effect of crosslinking in literature is ten years. When assuming no effect of crosslinking after ten years, the benefits in terms of gain in quality of life and prevented transplantations would be relatively small in relation to the costs of crosslinking (€54,384 per quality-adjusted life year). However, long term follow-up studies on crosslinking efficacy showed no trend towards a diminishing effect over time, and a stabilizing effect beyond ten years is regarded probable and reasonable. If a lifetime stabilizing effect of crosslinking was assumed crosslinking would be very cost-effective compared to standard management (€10,149 per quality-adjusted life year)

Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus

Daniel A Godefrooij, Mustapha El Kandoussi, Nienke Soeters, Robert PL Wisse Utrecht Cornea Research Group, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands Purpose: The purpose of this study was to compare the effects of transepithelial crosslinking (trans-CXL) versus epithelium-off crosslinking (epi-off CXL) for progressive keratoconus with respect to the development of higher order aberrations (HOAs) and their effects on visual acuity.Materials and methods: A total of 61 patients were randomized and examined preoperatively and 1, 3, 6, and 12 months postoperatively in an academic referral center. Total corneal HOAs were compared between the two treatment groups using mixed linear modeling. Types of HOAs (coma, trefoil, and spherical aberration) that differed between groups were entered in a multivariable analysis to test their effect on uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA).Results: The epi-off CXL group had more flattening in maximal keratometry compared to the trans-CXL group (P=0.02). UDVA did not differ significantly between the groups (P=0.59); however, CDVA was significantly more improved in the trans-CXL group (P=0.02). Horizontal trefoil improved more in the epi-off group compared to the trans-CXL group (P=0.04), whereas the other HOAs were virtually unchanged in both groups. Differences in changes in HOAs between the two groups had no effect on either UCVA (P=0.76) or CDVA (P=0.96).Conclusion: Although HOAs are clinically relevant determinants of vision quality in keratoconus patients, the change in total HOAs post treatment did not differ between the trans-CXL and epi-off CXL groups. Only horizontal trefoil differed significantly post treatment between the trans-CXL and epi-off CXL groups. However, this difference did not independently affect either UDVA or CDVA. Trans-CXL provides no benefit over epi-off CXL regarding visual relevant HOAs. Keywords: keratoconus, crosslinking, epithelium off, epithelium on, transepithelial, higher order aberrations, HOA