Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

INTRODUCTION: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. METHODS: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. RESULTS: We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. DISCUSSION: Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.

Corneal Collagen Cross-Linking in the Management of Keratoconus in Canada: A Cost-Effectiveness Analysis.

PURPOSE: To use patient-level microsimulation models to evaluate the comparative cost-effectiveness of early corneal cross-linking (CXL) and conventional management with penetrating keratoplasty (PKP) when indicated in managing keratoconus in Canada. DESIGN: Cost-utility analysis using individual-based, state-transition microsimulation models. PARTICIPANTS: Simulated cohorts of 100 000 individuals with keratoconus who entered each treatment arm at 25 years of age. Fellow eyes were modeled separately. Simulated individuals lived up to a maximum of 110 years. METHODS: We developed 2 state-transition microsimulation models to reflect the natural history of keratoconus progression and the impact of conventional management with PKP versus CXL. We collected data from the published literature to inform model parameters. We used realistic parameters that maximized the potential costs and complications of CXL, while minimizing those associated with PKP. In each treatment arm, we allowed simulated individuals to move through health states in monthly cycles from diagnosis until death. MAIN OUTCOME MEASURES: For each treatment strategy, we calculated the total cost and number of quality-adjusted life years (QALYs) gained. Costs were measured in Canadian dollars. Costs and QALYs were discounted at 5%, converting future costs and QALYs into present values. We used an incremental cost-effectiveness ratio (ICER = difference in lifetime costs/difference in lifetime health outcomes) to compare the cost-effectiveness of CXL versus conventional management with PKP. RESULTS: Lifetime costs and QALYs for CXL were estimated to be Can$5530 (Can$4512, discounted) and 50.12 QALYs (16.42 QALYs, discounted). Lifetime costs and QALYs for conventional management with PKP were Can$2675 (Can$1508, discounted) and 48.93 QALYs (16.09 QALYs, discounted). The discounted ICER comparing CXL to conventional management was Can$9090/QALY gained. Sensitivity analyses revealed that in general, parameter variations did not influence the cost-effectiveness of CXL. CONCLUSIONS: CXL is cost-effective compared with conventional management with PKP in the treatment of keratoconus. Our ICER of Can$9090/QALY falls well below the range of Can$20 000 to Can$100 000/QALY and below US$50 000/QALY, thresholds generally used to evaluate the cost-effectiveness of health interventions in Canada and the United States. This study provides strong economic evidence for the cost-effectiveness of early CXL in keratoconus.

Comparison of long-term outcomes of simultaneous accelerated corneal crosslinking combined with intracorneal ring segment or topography-guided PRK.

PURPOSE: To compare long-term outcomes of simultaneous accelerated corneal crosslinking (CXL) with intrastromal corneal ring segments (CXL-ICRS) with simultaneous accelerated CXL with topography-guided photorefractive keratectomy (CXL-TG-PRK) in progressive keratoconus (KC). SETTING: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Prospective nonrandomized interventional study. METHODS: The change in visual and topographical outcomes of CXL-ICRS and CXL-TG-PRK 4 to 5 years postoperatively were compared using linear regression models adjusted for preoperative corrected distance visual acuity (CDVA) and maximum keratometry (Kmax). RESULTS: 57 eyes of 43 patients with progressive KC who underwent simultaneous accelerated (9 mW/cm 2 , 10 minutes) CXL-ICRS (n = 32) and CXL-TG-PRK (n = 25) were included. Mean follow-up duration was 51.28 (9.58) and 54.57 (5.81) months for the CXL-ICRS and CXL-TG-PRK groups, respectively. Initial mean Kmax was higher in the CXL-ICRS group compared with the CXL-TG-PRK group (60.68 ± 6.81 diopters [D] vs 57.15 ± 4.19 D, P = .02). At the last follow-up, change (improvement) in logMAR uncorrected distance visual acuity (UDVA) compared with that preoperatively was significant with CXL-ICRS (-0.31 ± 0.27, P < .001, which is equivalent to approximately 3 lines) and not significant with CXL-TG-PRK (-0.06 ± 0.42, P = .43). The logMAR CDVA improved significantly with CXL-ICRS (-0.22 ± 0.20, P < .001), but not with CXL-TG-PRK (-0.05 ± 0.22, P = .25). Adjusting for baseline Kmax and CDVA, the improvement in UDVA was significantly greater with CXL-ICRS than with CXL-TG-PRK (-0.27, 95% CI, 0.06-0.47, P = .01). Improvement in CDVA was not significantly different. CONCLUSIONS: In this cohort of progressive KC with long-term follow-up, UDVA showed more improvement with accelerated CXL-ICRS than with CXL-TG-PRK.

Subjective and objective evaluation of corneal haze after accelerated corneal crosslinking for corneal ectasias.

PURPOSE: To evaluate the relationship between subjective (slit lamp examination [SLE]) and objective (densitometry) measurements of corneal haze after accelerated corneal crosslinking (aCXL), assess the relationship between densitometry and corrected distance visual acuity (CDVA), and determine the effect of baseline characteristics on densitometry after aCXL in eyes with progressive keratoconus and other ectasias. SETTING: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Retrospective analysis of a prospective interventional cohort study. METHODS: Scheimpflug-derived corneal densitometry, CDVA, maximum keratometry (Kmax ), and central corneal thickness were measured preoperatively and up to 1 year after aCXL, and post-operative haze was estimated with SLE (n = 483 eyes). A random effect model was used to examine the relationship between post-operative subjective haze with SLE and densitometry. Linear mixed models were used to examine the relationship between densitometry, pre-operative baseline characteristics, and CDVA. RESULTS: There was a significant association between subjective haze with SLE and densitometry (p < 0.001). There was a significant relationship between CDVA and densitometry: for every 10 GSUs of increased densitometry in the 0-2 mm zone, CDVA worsened by approximately half a Snellen line (p < 0.001). Age and pre-operative Kmax were significant predictors of densitometry. For every 10 years of age, densitometry increased by 0.68 GSUs (95% CI [0.27 to 1.07], p < 0.001). For every 10 D of increased preoperative Kmax , densitometry increased by 0.69 GSUs (95% CI [0.41 to 0.98], p < 0.001). CONCLUSIONS: Subjective haze after aCXL estimated with SLE, is significantly associated with densitometry. Increased densitometry after aCXL is associated with a reduction in CDVA.

Multi-center validation of Catquest-9SF visual function questionnaire in Ontario, Canada.

PURPOSE: To investigate the psychometric performance and responsiveness of Catquest-9SF, a patient-reported questionnaire developed to evaluate visual function as related to daily tasks, in patients referred for cataract surgery in Ontario, Canada. METHODS: This is a pooled analysis on prospective data collected for previous projects. Subjects were recruited from three tertiary care centers in Peel region, Hamilton, and Toronto, Ontario, Canada. Catquest-9SF was administered pre-operative and post-operatively to patients with cataract. Psychometric properties, including category threshold order, infit/outfit, precision, unidimensionality, targeting, and differential item functioning were tested using Rasch analysis with Winsteps software (v.4.4.4) for Catquest-9SF. Responsiveness of questionnaire scores to cataract surgery was assessed. RESULTS: 934 patients (mean age = 71.6, 492[52.7%] female) completed the pre- and post-operative Catquest-9SF questionnaire. Catquest-9SF had ordered response thresholds, adequate precision (person separation index = 2.01, person reliability = 0.80), and confirmed unidimensionality. The infit range was 0.75-1.29 and the outfit range was 0.74-1.51, with one item ('satisfaction with vision') misfitting (outfit value = 1.51). There was mistargeting of -1.07 in pre-operative scores and mistargeting of -2.43 in both pre- and post-operative scores, meaning that tasks were relatively easy for respondent ability. There was no adverse differential item functioning. There was a mean 1.47 logit improvement in Catquest-9SF scores after cataract surgery (p<0.001). CONCLUSION: Catquest-9SF is a psychometrically robust questionnaire for assessment of visual function in patients with cataract in Ontario, Canada. It is also responsive to clinical improvement after cataract surgery.

A randomized controlled trial comparing femtosecond-enabled deep anterior lamellar keratoplasty and standard deep anterior lamellar keratoplasty (FEDS Study).

OBJECTIVES: To compare outcomes of femtosecond-enabled deep anterior lamellar keratoplasty (FE-DALK) and standard deep anterior lamellar keratoplasty (S-DALK). METHODS: An open label, randomized controlled trial (Kensington Eye Institute, Toronto, ON, Canada) including 100 eyes of 97 participants with either keratoconus or corneal scarring, randomized to either FE-DALK (n = 48) or S-DALK (n = 49). PRIMARY OUTCOMES: postoperative astigmatism and surgically induced corneal astigmatism (SIA) - both at 15 months. SECONDARY OUTCOMES: 6-, 12- and 15-month postoperative uncorrected- and best spectacle-corrected visual acuity, steep and flat keratometry, manifest sphere and astigmatism, rate of conversion to penetrating keratoplasty (PK), big-bubble success, central corneal thickness, endothelial cell count and complications. RESULTS: In intention-to-treat analysis, mean postoperative astigmatism in the FE-DALK (n = 30) and S-DALK (n = 30) groups at 15 months was 7.8 ± 4.4 D and 6.3 ± 5.0 D, respectively (p = 0.282) with an adjusted mean difference of 1.3 D (95% CI -1.08, +3.65). Mean SIA (arithmetic) was 9.2 ± 7.8 and 8.8 ± 5.4 D, respectively (p = 0.838) with a mean difference of 0.4 D (95% CI -3.13, +3.85). In an analysis of successful DALK cases only, mean postoperative astigmatism in the FE-DALK (n = 24) and S-DALK (n = 20) groups at 15 months (after excluding 4 eyes with AEs) was 7.3 ± 4.4 and 6.2 ± 4.9 D, respectively (p = 0.531) with an adjusted mean difference of 0.9 D (95% CI -1.94, +3.71). Mean SIA (arithmetic) was 9.1 ± 7.8 and 7.9 ± 4.6 D, respectively (p = 0.547) with a mean difference of 1.2 D (95% CI -2.70,+5.02). Comparison of secondary outcomes showed only weak statistical evidence. CONCLUSIONS: In this randomized controlled trial, FE-DALK and S-DALK showed comparable functional and anatomical outcomes.

Ontario Cataract Quality Outcome Initiative: appropriateness and prioritization of cataract surgery.

OBJECTIVE: To explore the utility of the Catquest 9SF visual function (VF) questionnaire along with visual acuity (VA) for determining appropriateness and priority for cataract surgery. To evaluate the feasibility of administering the Catquest-9SF in a clinical setting using web-based electronic data capture and interpretation. DESIGN: Prospective multicentred interventional observational study. PARTICIPANTS: Subjects undergoing sequential cataract surgery in both eyes at 4 sites in Ontario. METHODS: We recorded best-corrected VA (BCVA) and VA with current correction (CCVA) in each eye and both eyes (OU) and Catquest-9SF responses on a tablet before and after cataract surgery. Linear regression models were employed to test for associations between VA and visual function (VF). RESULTS: Preoperative BCVA and CCVA in the worse eye were significant predictors of change in VF (p = 0.006 and p = 0.008, respectively); subjects with worse VA had a greater improvement in VF after surgery. There was a significant association between improvement in VF and improvement in CCVA OU (p = 0.001). Fourteen of 151 subjects (9%) had no improvement or worse VF scores after surgery. Within this group, 10 of 14 subjects had a preoperative score ≤-3, which is suggestive of minimal visual disability. Within this subset, 4 of 14 subjects (2.6%) had a preoperative BCVA of 20/30 or better in their worse eye. CONCLUSIONS: For patient groups with equal VA, the Catquest-9SF score can help determine priority for surgery. Web-based data capture and interpretation allow for efficient virtual assessments of VF. A BCVA in the worse eye of 20/30 or better combined with a Catquest-9SF score <-3 can be used as a guideline for lowest priority.

Patient Satisfaction and Visual Function Following Implantation of Trifocal or Extended Range of Vision Intraocular Lenses.

Purpose: To compare the trifocal TFNT00 and extended depth-of-focus (EDF) ZXR00 intraocular lenses (IOLs) with respect to overall satisfaction with near and distance vision, visual acuity, dysphotopsia symptoms, spectacle dependence, and mesopic best corrected contrast sensitivity (MBCCS). Materials and Methods: This non-randomized, retrospective, single-centre, comparative study took place at the Kensington Eye Institute in Toronto, Canada. Subjects implanted with either the TFNT00 IOL (n = 11) or ZXR00 IOL (n = 13) were assessed up to 4 years post operatively. Overall satisfaction with distance and near vision, corrected distance visual acuity, uncorrected visual acuity at distance, intermediate (60 cm) and near (40 cm) (UNVA), dysphotopsia symptoms, spectacle dependence and monocular MBCCS were evaluated. Results: Forty-eight eyes of 24 subjects (mean age 68 years, 54% female) were assessed. There was no difference in overall satisfaction; both groups had a median score of 10/10 for overall distance vision, and 7/10 and 8/10 for near vision for EDF and trifocal, respectively. MBCCS at the higher spatial frequencies was significantly better with the ZXR00 IOL. Potentially clinically relevant but not statistically significant differences were found; the trifocal group (vs the EDF group) had better binocular UNVA (20/24 vs 20/32) and less spectacle dependence at least some of the time (54% vs 85%). Conclusion: The ZXR00 may be preferred for those who want optimal contrast sensitivity in dim lighting. Consistent with previous studies, the TFNT00 trifocal IOL may be a better choice for those who want to optimize UNVA. More studies in North America are required to further investigate spectacle dependence.

Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Purpose: Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia). Study design: Prospective, multi-centre, observational study. Materials and methods: pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness. Results: A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 µm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness. Conclusion: The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 µm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.

Fellow Eye as a Predictor for Keratoconus Progression Following Accelerated Corneal Cross-linking.

PURPOSE: To assess the fellow eye as a predictor for keratoconus progression following bilateral same-day accelerated corneal cross-linking (A-CXL). METHODS: This was a post-hoc analysis of data from a prospective study of bilateral A-CXL for progressive keratoconus between 2013 and 2015. The primary outcome measures were absolute change in maximum keratometry (Kmax) (diopters [D]), relative change in Kmax (%), and A-CXL progression (increase in Kmax > 2.00 D). Responses in both eyes were measured by the change in Kmax, with the right eye serving as the "predictor" of progression for the left eye. RESULTS: Three-hundred ninety-two eyes (196 patients) with a mean age of 26.8 ± 7.7 years were included. There was a significant correlation in absolute and relative Kmax change (r = 0.26, P < .001 and r = 0.32, P < .001, respectively) between right and left eyes. In regression analysis, the only significant predictors of change in Kmax in the left eye were preoperative Kmax of the left eye (P < .02) and change in Kmax of the right eye (P < .001). Eyes that progressed in the right eye were more likely to progress in the left eye (29.4% versus 4.5%, odds ratio = 8.85, P < .001). In multiple regression, right eye progression of greater than 2.00 D was the significant predictor of left eye progression of greater than 2.00 D (odds ratio = 15.15, P < .007). CONCLUSIONS: This large-scale study of keratoconus following A-CXL indicates that patients with progression in the right eye were 15.5 times more likely to have progression in the left eye. Patients with progression following A-CXL in one eye should be closely observed due to increased risk of progression in the fellow eye. [J Refract Surg. 2021;37(3):186-191.].

Central versus paracentral cone location and outcomes of accelerated cross-linking in keratoconus patients.

PURPOSE: To compare outcomes 1 year after accelerated cross-linking (CXL) between keratoconus eyes with central cones to those with paracentral cones. METHODS: In this post hoc analysis of data from a prospective multicentre study, consecutive progressive keratoconus eyes treated with accelerated CXL were included. Preoperative and 1 year post CXL manifest refraction, corneal cylinder, maximal keratometry (Kmax), central corneal thickness and coma were assessed. Central and paracentral cones were defined as cones within the central 3 mm and those between 3 and 5 mm, respectively. Eyes with apical scarring and peripheral cones (>5 mm) were excluded. The primary outcome measures were changes in best spectacle-corrected visual acuity (BSCVA) and Kmax. RESULTS: Overall, 314 eyes (n = 314) with a mean age of 27.5 ± 7.7 years were included. At baseline, the central cone group was younger (p < 0.001), had lower corneal astigmatism (p = 0.03) and coma (p = 0.02). At 1 year post CXL, after adjusting for baseline characteristics (age, BSCVA, corneal astigmatism, Kmax and coma), the central cone group showed a greater reduction in myopia (mean difference 1.27 ± 0.60D, p = 0.04) and more improvement in BSCVA (mean difference 0.08 ± 0.02 logMAR, p < 0.001) compared to the paracentral group. There was no significant difference in progression rates between the central and paracentral groups (ΔKmax > 2D, 6.7% vs. 6.5%, respectively, p = 0.83). CONCLUSIONS: This large-scale study of keratoconus eyes 1 year after accelerated CXL indicates that compared to those with paracentral cones, central cones have on average almost one additional line improvement in BCSVA and 1.27 D more reduction in myopia.

Factors affecting central corneal thickness measurement agreement between Scheimpflug imaging and ultrasound pachymetry in keratoconus.

PURPOSE: To evaluate the agreement of central corneal thickness (CCT) measurement between Scheimpflug imaging and ultrasound (U/S) pachymetry in keratoconic eyes, and investigate factors that affect the agreement. METHODS: This post hoc analysis within a prospective, observational non-randomised study preformed at the Kensington Eye Institute, Toronto, Ontario, Canada, included crosslinking candidates with progressive keratoconus (KC). Main outcome measures were the agreement of CCT measurement between Scheimpflug imaging (Pentacam Oculus, Wetzlar, Germany) and U/S pachymetry (PachPen 24-5100, Accutome Inc., Malvern, Pennsylvania, USA), and factors that affect the agreement. RESULTS: A total of 794 keratoconic eyes of 456 subjects with a mean age of 27.6±8.0 years (69.7% males and 49.6% right eyes) were included. Agreement between devices was moderate (intraclass correlation coefficient: 74.9%, Bland-Altman limits of agreement: -48.5 µm to +62.5 µm). In a multivariable analysis, cone decentration (p<0.001, coefficient +10.13 [+6.73 to +13.53 95% CIs]) and Kmax (p<0.001, coefficient +0.68 [+0.46 to +0.90 95% CIs]) were significantly associated (both clinically and statistically) with the level of agreement between the devices; the discrepancy in CCT between the devices increased on average by 10.13 µm for every mm of cone decentration, and by 6.8 µm for every 10D of Kmax. Age, corneal astigmatism and spherical equivalent were statistically but not clinically significant factors affecting agreement. CONCLUSION: The agreement of CCT measurement between Scheimpflug imaging and U/S pachymetry in KC was moderate. To ensure the safety of crosslinking in keratoconic corneas, Scheimpflug and U/S CCT measurements should not be used interchangeably, especially in steep corneas and corneas with decentred cones.

Vision to improve: quality improvement in ophthalmology.

Improving quality of care and patient outcomes is a professional duty of all health care workers. Quality improvement is a part of health policy, an accreditation requirement of residency programs, and a recognized sub-specialty in academic medicine. Given the increasing need for ophthalmological services with our aging population, it is critical for ophthalmologists and their staff to develop the necessary skills in quality improvement to ensure access to care that is safe, patient-centered, effective, efficient, equitable, and timely. This narrative review outlines tools that are used in a recognized framework, including the creation of an aim statement, Ishikawa diagram, Pareto analysis, process maps, Plan-Do-Study-Act cycles, and run charts. We also discuss common challenges that occur when conducting quality initiatives. Two quality improvement projects conducted in the Department of Ophthalmology at University of Toronto are used as examples to illustrate these tools. The aim of the first project was to improve visual field test reliability and the aim of the second was to ensure secure email communication between residents and staff in caring for emergency patients. This primer provides the foundations ophthalmologists and their staff can use to support and guide their quality improvement efforts.

Validation and application of Catquest-9SF in various populations: A systematic review.

Cataract is a common cause of reversible blindness. Visual acuity alone is not enough to assess appropriateness for surgery, prioritization, and outcomes. Catquest-9SF questionnaire evaluates patients' self-assessed visual function as related to daily tasks. We summarize and assess the validity of Catquest-9SF as a patient-reported outcome questionnaire to determine its suitability for clinical use. Thirteen studies with sample sizes ranging 102-10,886 (total n = 15,289) undertaken from 2009 to 2018 were included. Catquest-9SF showed unidimensionality, ordered response thresholds, and acceptable precision in all studies. Nine studies had significant mistargeting (range 0.66 to -2.04); the tasks being easy relative to the respondent ability in most studies. Two studies had misfitting items. We conclude Catquest-9SF is a valid and reliable tool to measure visual function in patients with cataract in various populations. Because results can be population specific, it is recommended that Catquest-9SF be validated in a new population before it is incorporated in routine practice.

Accelerated Corneal Cross-Linking: Efficacy, Risk of Progression, and Characteristics Affecting Outcomes. A Large, Single-Center Prospective Study.

PURPOSE: We examined the efficacy and preoperative characteristics that affect outcomes of accelerated (9 mW/cm2 for 10 minutes) corneal cross-linking (CXL). DESIGN: Prospective single-center observational cohort study. METHODS: We enrolled 612 eyes of 391 subjects with progressive keratoconus (n = 589), pellucid marginal degeneration (n = 11), and laser in situ keratomileusis-induced ectasia (n = 12). We evaluated best spectacle-corrected visual acuity (BSCVA), topography, refraction, endothelial cell density, corneal thickness, haze, intraocular pressure, and visual function before and 12 months after the CXL procedure. We tabulated the proportion of those with progression of maximum keratometry (Kmax). We included participant's race, age, sex, and the presence of preoperative apical scarring and environmental allergies in a multivariable linear regression model to determine the effect of these characteristics on outcomes. RESULTS: At 1 year there was no significant change in mean Kmax (n = 569). Progression of Kmax was higher in subgroups with a baseline Kmax >58 diopters (n = 191) and those 14-18 years of age (n = 53). Preoperative BSCVA, Kmax, refraction, corneal cylinder, coma, central corneal thickness, and vision function were statistically and clinically significant predictors of outcomes (P < .001). Preoperative apical scarring led to worsening haze (P = .0001), more astigmatism (P = .002), more central corneal thinning (P = .002), and was protective to the endothelium (P = .008). Race, age, and sex affected some outcomes. CONCLUSION: Mean Kmax was stable at 1 year after accelerated CXL. Younger patients and those with a higher preoperative Kmax need to be monitored closely for progression. Preoperative BSCVA, topography, refraction, CCT, and apical scarring were significant predictors of outcomes.

A recommended "minimum data set" framework for SD-OCT retinal image acquisition and analysis from the Atlas of Retinal Imaging in Alzheimer's Study (ARIAS).

INTRODUCTION: We propose a minimum data set framework for the acquisition and analysis of retinal images for the development of retinal Alzheimer's disease (AD) biomarkers. Our goal is to describe methodology that will increase concordance across laboratories, so that the broader research community is able to cross-validate findings in parallel, accumulate large databases with normative data across the cognitive aging spectrum, and progress the application of this technology from the discovery stage to the validation stage in the search for sensitive and specific retinal biomarkers in AD. METHODS: The proposed minimum data set framework is based on the Atlas of Retinal Imaging Study (ARIAS), an ongoing, longitudinal, multi-site observational cohort study. However, the ARIAS protocol has been edited and refined with the expertise of all co-authors, representing 16 institutions, and research groups from three countries, as a first step to address a pressing need identified by experts in neuroscience, neurology, optometry, and ophthalmology at the Retinal Imaging in Alzheimer's Disease (RIAD) conference, convened by the Alzheimer's Association and held in Washington, DC, in May 2019. RESULTS: Our framework delineates specific imaging protocols and methods of analysis for imaging structural changes in retinal neuronal layers, with optional add-on procedures of fundus autofluorescence to examine beta-amyloid accumulation and optical coherence tomography angiography to examine AD-related changes in the retinal vasculature. DISCUSSION: This minimum data set represents a first step toward the standardization of retinal imaging data acquisition and analysis in cognitive aging and AD. A standardized approach is essential to move from discovery to validation, and to examine which retinal AD biomarkers may be more sensitive and specific for the different stages of the disease severity spectrum. This approach has worked for other biomarkers in the AD field, such as magnetic resonance imaging; amyloid positron emission tomography; and, more recently, blood proteomics. Potential context of use for retinal AD biomarkers is discussed.

Comparison of accelerated CXL alone, accelerated CXL-ICRS, and accelerated CXL-TG-PRK in progressive keratoconus and other corneal ectasias.

PURPOSE: To compare accelerated corneal crosslinking (CXL) alone, CXL with simultaneous intrastromal corneal ring segments (CXL-ICRS), and CXL with simultaneous topography-guided photorefractive keratectomy (CXL-TG-PRK) in progressive keratoconus, pellucid marginal degeneration (PMD), or laser in situ keratomileusis (LASIK)-induced ectasia. SETTING: The Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Prospective nonrandomized interventional study. METHODS: Visual and topographical outcomes using a comparative analysis adjusting for preoperative maximum keratometry (Kmax) were evaluated 1 year postoperatively. RESULTS: Four hundred fifty-two eyes from 375 patients with progressive keratoconus, PMD, or LASIK-induced ectasia that underwent accelerated (9 mW/cm, 10 minutes) CXL alone (n = 204), CXL-ICRS (n = 126), or CXL-TG-PRK (n = 122) were included. Change in logarithm of the minimum angle of resolution uncorrected distance visual acuity was significant with CXL-ICRS (-0.31; 95% CI, -0.38 to -0.24) and CXL-TG-PRK (-0.16; 95% CI, -0.24 to -0.09), but not with CXL alone. No significant differences in change were found between the 3 groups. Change in corrected distance visual acuity (CDVA) was significant in all 3 groups: -0.12 (95% CI, -0.15 to -0.10) with CXL alone, -0.23 (95% CI, -0.27 to -0.20) with CXL-ICRS, and -0.17 (95% CI, -0.21 to -0.13) with CXL-TG-PRK. Improvement in CDVA was greater with CXL-ICRS than with CXL alone (-0.08 ± 0.02; P < .0001) and CXL-TG-PRK (-0.05 ± 0.02; P = .005). Change in Kmax was significant with CXL-ICRS [-3.21 diopters (D); 95% CI, -3.98 to -2.45] and CXL-TG-PRK (-3.69 D; 95% CI, -4.49 to -2.90), but not with CXL alone (-0.05 D; 95% CI, -0.66 to 0.55). CONCLUSIONS: CXL alone might be best for keratoconic patients who meet the inclusion criteria. CXL-ICRS might be more effective for eyes with more irregular astigmatism and worse CDVA and CXL-TG-PRK for eyes requiring improvements in irregular astigmatism but still have good CDVA.

Risk factors for acute endophthalmitis after cataract surgery: a population-based study.

OBJECTIVE: To identify risk factors for suspected acute endophthalmitis after cataract surgery. DESIGN: Population-based retrospective cohort. PARTICIPANTS: Administrative data from more than 440,000 consecutive cataract surgeries in Ontario, Canada, from April 1, 2002, to March 31, 2006. METHODS: Consecutive physician billing claims for cataract surgery and specific intraoperative and postoperative procedures related to complications of cataract surgery were identified. Acute endophthalmitis was defined using surrogate markers for intraocular infection, including vitrectomy, vitreous injection, or aspiration procedures not in combination with air/fluid exchange or dislocated lens extraction, performed 1 to 14 days after cataract surgery. Anterior vitrectomy performed on the day of surgery was used as a surrogate marker for capsular rupture. MAIN OUTCOME MEASURES: Overall rates of endophthalmitis were calculated and grouped by patient demographics, surgical facility, season, year, and association with capsular rupture. RESULTS: There were 617 suspected acute endophthalmitis cases of 442,177 cataract surgeries over the 4 years. The overall unadjusted and adjusted rates of suspected acute endophthalmitis were both 1.4 per 1000 cataract surgeries. Men had higher rates than women (1.70 vs. 1.19/1000 surgeries, P<0.0001) with an adjusted odds ratio of 1.40 (95% confidence interval, 1.19-1.64).The oldest age group (>or= 85 years) had the highest rate (2.18/1000), and the youngest group (20-64) had the second highest rate (1.76/1000). The endophthalmitis rates for these age groups were significantly different from those aged 65 to 84 years. The endophthalmitis rate was approximately 10-fold higher in those with capsular rupture compared with those without (13.11 vs. 1.34/1000, P<0.0001), with an adjusted odds ratio of 9.56 (95% confidence interval, 6.43-14.2). CONCLUSIONS: The overall rates of suspected acute endophthalmitis are low but significantly higher in certain patient groups. Our population-based analysis can be used as a benchmark for quality-improvement initiatives and can assist clinicians in educating their patients regarding the risks associated with cataract surgery. Future work is required to address the higher rate of endophthalmitis in men, those with capsular rupture, and the oldest patients undergoing cataract surgery.

Association between tamsulosin and serious ophthalmic adverse events in older men following cataract surgery.

CONTEXT: Both benign prostatic hyperplasia (BPH) and cataract formation are common in older men. The alpha-adrenergic receptor blocker tamsulosin is frequently prescribed to treat BPH, and research suggests this drug may increase the intraoperative difficulty of cataract surgery. No studies have documented whether use of tamsulosin or other alpha-blocker drug therapies affect the risk of serious postoperative adverse events. OBJECTIVE: To assess the risk of adverse events following cataract surgery in older men prescribed tamsulosin or other alpha-blocking drugs used to treat BPH. DESIGN, SETTING, AND PATIENTS: Nested case-control analysis of a population-based retrospective cohort study using linked health care databases from Ontario, Canada. We included all men aged 66 years or older who had cataract surgery between 2002 and 2007 (N = 96 128). MAIN OUTCOME MEASURES: A composite of procedures signifying retinal detachment, lost lens or lens fragment, or endophthalmitis occurring within 14 days after cataract surgery. The risk of these adverse events was compared between men treated with tamsulosin or other alpha-blockers and men with no exposure to these medications in the year prior to cataract surgery. We separately examined the association of drug exposure that was either recent (within the 14 days before surgery) or previous (15-365 days before surgery). RESULTS: Overall, 3550 patients (3.7%) in the cohort had recent exposure to tamsulosin and 7426 patients (7.7%) had recent exposure to other alpha-blockers. Two hundred eighty-four patients (0.3%) had an adverse event. We randomly matched 280 of the cases to 1102 controls according to their age, surgeon, and year of surgery. Adverse events were significantly more common among patients with recent tamsulosin exposure (7.5% vs 2.7%; adjusted odds ratio [OR], 2.33; 95% confidence interval [CI], 1.22-4.43) but were not associated with recent exposure to other alpha-blockers (7.5% vs 8.0%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to previous exposure to either tamsulosin (< or = 1.8% vs 1%; adjusted OR, 0.94; 95% CI, 0.27-3.34) or other alpha-blockers (2.9% vs 2.1%; adjusted OR, 1.08; 95% CI, 0.47-2.48). This corresponds to an estimated number needed to harm (NNH) of 255 (95% CI, 99-1666). CONCLUSIONS: Exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events. There were no significant associations with exposure to other alpha-blocker medications used to treat BPH.