Extremely asymmetric ectasia:Tomographically unilateral keratoconus

Purpose: To investigate the characteristics of apparently stable forms of tomographically unilateral keratoconus (KC). Methods: In this retrospective case–control study, strict unilaterality criteria were applied to select tomographically unilateral cases with ≥3 years of follow-up. For comparison, a healthy cohort and two bilateral KC cohorts were matched to the tomographically unilateral cases. All patients were selected from The Rotterdam Eye Hospital, whereas healthy controls were selected from the population-based Rotterdam Study. After cohort selection, several risk factors and 25 Pentacam features were assessed. Unaffected (i.e. tomographically non-keratoconic) eyes from the tomographically unilateral cases were compared to matched healthy eyes, matched bilateral KC eyes and affected unilateral KC eyes. Furthermore, affected tomographically unilateral KC eyes were compared to matched bilateral KC eyes. Statistical analysis relied on Wilcoxon signed-rank tests and conditional logistic regression. Results: From 1006 assessed cases, 18 (1.8%) tomographically unilateral cases were selected. Their median (interquartile range) follow-up was 5.7 (4.3–8) years. Eczema and asthma were more prevalent among tomographically unilateral patients (28% each) compared to bilateral patients (6% and 9%) (p = 0.01 and p = 0.05, signed-rank test). We could not detect meaningful Pentacam differences between unaffected unilateral eyes and matched healthy eyes. Expectedly, significant differences were detected between unaffected unilateral eyes and affected (bilateral or unilateral) eyes. Lastly, the ectatic features of affected unilateral eyes seemed comparable to their bilateral counterparts, but their high-order aberrations were significantly lower. Conclusion: Our findings support the existence of tomographically unilateral KC. Understanding how tomographic unilaterality ensues may offer valuable insights into KC aetiology.</p

Climate Determinants of Keratoconus:Insights From a Systematic Review of Prevalence

Purpose: The reported prevalence of keratoconus varies widely worldwide, but the causes of this variation are not well understood. We therefore aimed to explore the potential impact of local climate variables on keratoconus prevalence. Methods: The worldwide prevalence of clinical keratoconus in the general population was systematically reviewed. In each eligible prevalence area, four climate variables deemed possibly relevant to keratoconus were assessed: daily maximum temperature, relative humidity, ultraviolet radiation, and wind speed. Climate variables were calculated using worldwide gridded climate datasets from the European Center of Medium-Range Weather Forecasts. Population density weighting was applied to enhance exposure accuracy. The average of each climate variable was calculated over the 10 years preceding data collection of each study. The potential impact of those climate variables was investigated using multiple linear regression adjusted for the gross domestic product per capita (based on purchasing power parity) with the natural logarithm of prevalence as the outcome variable. Results: Sixteen eligible studies were identified. After filtering to retain one prevalence estimate per region, 11 studies including datapoints from 61 areas were analyzed. The median (interquartile range) prevalence of keratoconus was 0.10% (0.07%-0.19%). Multiple regression revealed a significant negative association between humidity and keratoconus prevalence (β = -0.03; 95% confidence interval, -0.06 to -0.01; P = 0.004). In contrast, the other analyzed climate variables were not significantly associated with keratoconus prevalence.Conclusions: Using global gridded climate maps, we observed a significant and biologically plausible link between low humidity and keratoconus. This suggests that humidification could benefit patients and at-risk groups.</p

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease

Applying Computerized Adaptive Testing to the FACE-Q Skin Cancer Module: Individualizing Patient-Reported Outcome Measures in Facial Surgery

Background: Skin cancer is among the most frequently occurring malignancies worldwide, which creates a great need for an effective patient-reported outcome measure. Providing shorter questionnaires reduces patient burden and increases patients' willingness to complete forms. The authors set out to use computerized adaptive testing to reduce the number of items needed to predict results for scales of the FACE-Q Skin Cancer Module, a validated patient-reported outcome measure that measures health-related quality of life and patient satisfaction in facial surgery. Methods: Computerized adaptive testing generates tailored questionnaires for patients in real time based on their responses to previous questions. The authors used an open-source computerized adaptive testing simulation software to run item responses for the five scales from the FACE-Q Skin Cancer Module (i.e., scar appraisal, satisfaction with facial appearance, appearance-related psychosocial distress, cancer worry, and satisfaction with information about appearance). Each simulation continued to administer items until prespecified levels of precision were met, estimated by standard error. Mean and maximum item reductions between the original fixed-length short forms and the simulated versions were evaluated. Results: The number of questions that patients needed to answer to complete the FACE-Q Skin Oncology Module was reduced from 41 items in the original form to a mean of 23 +/- 0.55 items (range, 15 to 29) using the computerized adaptive testing version. Simulated computerized adaptive testing scores maintained a high correlation (0.98 to 0.99) with the score from the fixed-length short forms. Conclusions: Applying computerized adaptive testing to the FACE-Q Skin Cancer Module can reduce the length of assessment by more than 50 percent, with virtually no loss in precision. It is likely to play a critical role in the implementation in clinical practice

Different keratoconus definitions can lead to substantial prevalence disparities in population-based studies

Abstract This report explores the prevalence of keratoconus in a population-based cohort of adults aged 40 or older according to ten different definitions. All Rotterdam Study participants with reliable Pentacam scans and no prior corneal refractive surgery were cross-sectionally analysed (n = 2660). First, we applied a novel evidence-based definition. Suspected keratoconus was defined as having at least one eye with a final D-index (BAD-D) ≥ 2.6. Manifest keratoconus was defined as having at least one eye with: (1) BAD-D ≥ 2.6; and (2) a score of at least 4/10 on the novel Rotterdam Keratoconus Scale (RKS); and (3) a confirming assessment of the relevant Pentacam maps; and (4) meeting Holladay’s criteria in case of recent contact lens usage. Using this proposed definition, 72 participants (2.71%, 95%CI: 2.16–3.40%) had suspected keratoconus, while 10 participants (0.38%, 95%CI: 0.20–0.69%) had manifest keratoconus. To assess reproducibility, two specialists independently applied the proposed definition, with a substantial inter-observer agreement (Kappa = 0.74). Interestingly, 6(60%) patients were unaware of having keratoconus. Applying nine alternative definitions from similar screening studies produced prevalence estimates ranging from 0.19 to 9.29% in the same cohort. Moreover, counting solely on a BAD-D cutoff of 2.6 to define keratoconus was unreliable, with a low positive predictive value of 14%. These findings explain partially the large heterogeneity in the reported keratoconus prevalences, underscoring the need for a standardized definition

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease