Five-year corneal cross-linking outcomes: A Save Sight Keratoconus Registry Study.

BACKGROUND: We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients. METHODS: An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes. RESULTS: There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p < 0.001) in year 1, and 6.9 (p < 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p < 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years. CONCLUSIONS: Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

Acute disseminated encephalomyelitis with bilateral optic neuritis following ChAdOx1 COVID-19 vaccination.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory demyelinating disease of the central nervous system. We report a case of ADEM presenting with bilateral optic neuritis temporally associated with the ChAdOx1 vaccine against SARS-COVID19 virus. CASE PRESENTATION: A 36-year-old female presented with bilateral optic neuritis following her first dose of the ChAdOx1 vaccine. Initial MRI Brain showed evidence of demyelination within the subcortical white matter, with no radiological involvement of the optic nerves. Visual evoked potentials were consistent with bilateral optic neuritis which was confirmed radiologically on follow up MRI. She was treated with intravenous steroids with improvement both in symptoms and radiological appearance. A pseudo-relapse occurred which was treated with a further course of intravenous steroids followed by an oral taper. The clinical, radiological and serological results were most consistent with diagnosis of ADEM. CONCLUSIONS: ADEM is an exceedingly rare complication of ChAdOx1 vaccine despite millions of doses. While it is imperative clinicians remain aware of neurological complications of vaccines, the importance of vaccination to control a pandemic should not be undermined.

Predictors of progression in untreated keratoconus: a Save Sight Keratoconus Registry study.

AIMS: We set out to identify risk factors for progression in untreated keratoconus patients from 34 centres across Australia, New Zealand, Spain and Italy. METHODS: Patients were divided into 'progressors' and 'stable' patients for each clinical parameter: visual acuity (VA), steepest keratometry (maximum keratometry (Max-K)) and thinnest corneal thickness (TCT). Primary outcomes were the proportion of eyes with sustained progression in VA, Max-K or TCT within 3 years. Secondary outcomes included predictors of progression. RESULTS: There were 3994 untreated eyes from 2283 patients. The proportion of eyes with VA, Max-K and TCT progression at 1 year were 3.2%, 6.6% and 3.1% respectively. Factors associated with VA loss were higher baseline VA (HR 1.15 per logMAR line increase in VA; p<0.001) and steeper baseline Max-K (HR 1.07 per 1D increase; p<0.001). Younger baseline age was associated with Max-K steepening (HR 0.96 per year older; p=0.001). Thicker baseline TCT, steeper baseline Max-K and younger baseline age were associated with TCT thinning: (HR 1.08 per 10 µm increase in TCT; p<0.001), (HR 1.03 per 1D increase; p=0.02) and (HR 0.98 per year younger; p=0.01), respectively. CONCLUSIONS: Steeper Max-K and younger age were the most clinically useful baseline predictors of progression as they were associated with worsening of two clinical parameters. Every 1D steeper Max-K was associated with a 7% and 3% greater risk of worsening VA and thinning TCT, respectively. Each 1 year younger was associated with a 4% and 2% greater risk of steepening Max-K and thinning TCT, respectively.

Comparative Efficacy and Safety of Standard Versus Accelerated Corneal Crosslinking for Keratoconus: 1-Year Outcomes From the Save Sight Keratoconus Registry Study.

PURPOSE: The aim of this study was to compare the efficacy and safety of standard [Ultraviolet (UV) light power: 3 mW/cm2, duration: 30 minutes] versus accelerated (UV power: 9 mW/cm2, duration: 10 minutes) corneal crosslinking (CXL) for stabilizing keratoconus. METHODS: A total of 684 eyes (555 patients; mean age ± SD, 25.0 ± 7.9 years; women, 30.6%) from 24 international sites with epithelium-off CXL for keratoconus had follow-up data at 1-year and met the inclusion criteria. Two hundred sixty-six eyes (228 patients) had undergone standard CXL, and 418 eyes (327 patients) had undergone accelerated CXL. The outcome measures included changes in visual acuity, keratometry, minimum corneal thickness, and frequency of adverse events. The outcomes were compared using mixed-effects regression models adjusted for age, sex, visual acuity, keratometry, pachymetry, doctor, practice, and eye laterality. RESULTS: The adjusted mean changes (95% confidence interval) in outcomes were similar in standard and accelerated CXL in visual acuity [6.5 (2.0, 11.1) versus 5.5 (0.4, 10.6) logMAR letters, respectively], Kmax [-0.9 (-1.4, -0.3) D versus -1.2 (-1.9, -0.4) D, respectively], K2 [-0.4 (-0.9, 0.2) D versus -0.4 (-1.1, 0.3), D respectively], or minimum corneal thickness [-13.3 (-20.3, -6.3) µm versus -16.6 (-24.5, -8.6) µm, respectively] (all P > 0.05). The frequency of adverse events at the 12-month visit was also similar between the CXL groups (standard, 8.3% vs. accelerated, 5.5%; P = 0.21). CONCLUSIONS: This real-world observational study found that both standard and accelerated CXL were similarly safe and effective in stabilizing keratoconus at 1-year postsurgery in the real-world setting. The findings support the adoption of accelerated CXL for time and convenience.

Psychometric Properties of the Keratoconus Outcomes Research Questionnaire: A Save Sight Keratoconus Registry Study.

PURPOSE: The aim of this study was to evaluate the psychometric properties of the Keratoconus Outcomes Research Questionnaire (KORQ) in patients enrolled in the Save Sight Keratoconus Registry. METHODS: A cross-sectional study was conducted utilizing prospectively collected web-based registry data. The psychometric properties of the KORQ were assessed using both classical test theory and Rasch analysis. Andrich group rating scale variant of the Rasch analysis was conducted using Winsteps software, Version 3.92.1. RESULTS: The KORQ was completed by 189 patients with keratoconus (men, 67.7%; white, 69.8%; median age 29 years; better eye median values: visual acuity, 75 LogMAR letters; Kmax, 51.3 D; K2, 46.5 D; thinnest pachymetry, 485 µm). Cronbach's α for the "Activity Limitation" and "Symptoms" scales were 0.95 and 0.91, respectively, with both scales free from floor or ceiling effects. On Rasch analysis, the category thresholds were ordered and well-spaced for both scales. The Activity Limitation scale had excellent psychometric properties including person separation index (3.6), unidimensionality (variance explained, 65.4%), fit statistics (<1.3 MnSq), and measurement range (3.6 logits). Similarly, the Symptoms scale had satisfactory psychometric properties including person separation index (2.5), unidimensionality (variance explained, 54.3%), fit statistics (<1.30 MnSq except for 1 item), and measurement range (2.0 logits). Both scales were well targeted to the population and free of differential item functioning. CONCLUSIONS: The KORQ is a psychometrically robust patient-reported outcome measure for evaluating quality of life parameters in keratoconus. It enables routine collection and monitoring of meaningful patient-reported outcome data in clinical settings, including registries.

The Impact on Work Patterns of Implementing the Save Sight Keratoconus Registry in the Hospital Setting.

PURPOSE: The adoption of clinical registries has the potential to improve outcomes, while reducing the costs of health care. We sought to evaluate the changes in workflow that occurred with implementation of the Save Sight Keratoconus Registry (SSKR) in corneal clinics. METHODS: A prospective time-motion study and a clinician survey were conducted. The timing of clinic consultations was recorded before and after implementation of the SSKR. The activities were assigned into 3 main categories: 1) direct patient care (eg, talking to, examining), 2) indirect patient care (record keeping), and 3) indirect patient care (reading). RESULTS: Overall, there was no change in average time spent per patient with or without the SSKR; 12.3 (5.3 SD) versus 12.1 (5.3 SD) minutes, respectively, P = 0.84. There was no change in time spent providing direct care with or without the SSKR; 5.4 (2.8 SD) versus 5.9 (2.8 SD) minutes, respectively, P = 0.51. Within direct patient care, there was no impact with or without the SSKR on the time spent examining (1.9 [1.0 SD] vs. 1.9 [1.4 SD] minutes, respectively, P = 0.58) or talking to patients (3.5 [2.3 SD] vs. 4.1 [2.3 SD] minutes, respectively, P = 0.21). Indirect care time was unchanged overall for record keeping (3.2 [2.2 SD] vs. 4.6 [2.9 SD], respectively, P = 0.16) and reading tasks (3.1 [1.8 SD] vs. 2.0 [1.3 SD], respectively, P = 0.09). CONCLUSIONS: The SSKR was implemented into clinical practice without affecting the total consultation time, time spent directly interacting with patients, or use of patient records. Our findings support that registries requiring data entry could be widely adopted into routine clinical practice.

Keratoconus Natural Progression: A Systematic Review and Meta-analysis of 11 529 Eyes.

PURPOSE: We set out to describe the natural history of keratoconus. We included untreated patients, and our key outcome measures were vision, refraction, and corneal curvature. CLINICAL RELEVANCE: Keratoconus affects 86 in 100 000 people, causing visual loss due to increasing irregular corneal astigmatism, and the quality of life declines in patients. Interventions are used to stabilize the disease or improve vision, including corneal cross-linking (CXL) and grafting, but these carry risks. Detailed knowledge of the natural history of keratoconus is fundamental in making informed decisions on when their benefits outweigh these risks. METHODS: We included prospective or retrospective studies of pediatric or adult patients who reported 1 or more of visual acuity, refraction, and corneal curvature measures: steep keratometry (K2), mean keratometry (Kmean), or maximum keratometry (Kmax), thinnest pachymetry, corneal transplantation rates, corneal scarring incidence, and patient-reported outcome measures (PROMs). Databases analyzed included Medline, Embase, CENTRAL, and CINAHL. Searches were carried out until October 2018. Bias assessment was carried out using the Joanna Briggs Institute model of evidence-based healthcare. RESULTS: Our search yielded 3950 publication titles, of which 41 were included in our systematic review and 23 were incorporated into the meta-analysis. Younger patients and those with greater Kmax demonstrated more steepening of Kmax at 12 months. The meta-analysis for Kmax demonstrated a significant increase in Kmax of 0.7 diopters (D) at 12 months (95% confidence interval [CI], 0.31-1.14; P = 0.003). Our meta-regression model predicted that patients had 0.8 D less Kmax steepening over 12 months for every 10-year increase in age (P = 0.01). Patients were predicted to have 1 D greater Kmax steepening for every 5 D of greater baseline Kmax (P = 0.003). At 12 months, there was a significant increase in the average Kmean of 0.4 D (95% CI, 0.18-0.65; P = 0.004). CONCLUSIONS: We report the first systematic review and meta-analysis of keratoconus natural history data including 11 529 eyes. Younger patients and those with Kmax steeper than 55 D at presentation have a significantly greater risk of progression of keratoconus. Closer follow-up and a lower threshold for cross-linking should be adopted in patients younger than 17 years and steeper than 55 D Kmax.

Vision-Related Quality of Life in Keratoconus: A Save Sight Keratoconus Registry Study.

PURPOSE: To assess vision-related quality of life using the Impact of Vision Impairment Questionnaire (IVI) in patients with keratoconus enrolled in the Save Sight Keratoconus Registry. METHODS: In this cross-sectional study, data on 107 keratoconic patients were collected through a prospectively designed web-based registry from a quaternary referral eye hospital and 2 corneal subspecialty practices. Vision-related quality of life was evaluated using the IVI. Rasch analysis was used to transform the IVI responses into interval-level measures comprising reading, mobility, and emotional well-being subscales. Associations between best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), and pachymetry for each eye and IVI subscale scores were evaluated with univariate (Pearson correlations) and multivariable regression adjusted for age and gender. RESULTS: Of the 107 patients, 37 (34.5%), 41 (38.0%) and 29 (26.9%) had mild, moderate, and severe keratoconus, respectively. On uni- and multivariable analysis, BCVA in the better eye had the strongest association with reading [r = 0.51; 95% confidence interval (CI), 0.35-0.64, P = 0.004] and mobility (r = 0.55; 95% CI, 0.41-0.67, P < 0.001) subscale scores. BCVA in the better and worse eye, both had the joint strongest associations with emotional scores on univariate analysis, but only the latter was significant on multivariable analysis (r = 0.37; 95% CI, 0.20-0.53, P < 0.001). K2 and Kmax in the better eye also displayed significant associations with reading and mobility scores. CONCLUSIONS: In patients with keratoconus, BCVA in the better eye had the strongest correlation with reading and mobility scores, whereas BCVA in the worse eye was significantly correlated with emotional scores.

Outcomes of adjustable strabismus surgery in an Irish University Hospital.

PURPOSE: Strabismus surgery aims to improve binocular vision, reduce diplopia, and enhance cosmesis. Adjustable strabismus procedures have been developed as a means of tackling unpredictability in some post-operative results. The purpose of the study was to compare the effectiveness of adjustable and non-adjustable squint procedures in the treatment of strabismus. METHODS: We analyzed adjustable or non-adjustable squint surgery undergone in our Irish locality by retrospectively studying 27 consecutive patients at Mater Misericordiae University Hospital, Dublin. RESULTS: There was no significant difference (p = 0.519) in the mean post-operative horizontal deviation between the adjustable group (mean = 11.6 PD) and the non-adjustable group (mean = 15.3 PD). We found that adjustable procedures resulted in a trend (p = 0.050) towards a greater mean horizontal effect per muscle (18.9 PD per muscle) than non-adjustable procedures (mean 9.7 PD). We went on to analyze the adjustable group in order to determine the impact on outcome in those patients in whom their adjustable sutures were manipulated postoperatively. Of the 11 patients who underwent adjustable procedures, 6 subsequently had adjustments made as planned and 5 did not require adjustment. Those patients who had their sutures adjusted demonstrated a smaller mean post-operative deviation (8.5 PD) than those patients in whom their suture was not adjusted (mean = 16.3 PD). CONCLUSION: Our study displays a trend that adjustable procedures are more effective in terms of the mean horizontal effect per muscle operated, and is a novel way of reporting effectiveness of strabismus procedures.