Background:Ocular hypertension, that is intraocular pressure > 21 mmHg, is a risk factor for glaucoma. A glaucoma risk predictor, the Ocular Hypertension Study-European Glaucoma Prevention Study model, is available. Objectives:(1) To validate and update the Ocular Hypertension Study-European Glaucoma Prevention Study risk prediction model in a United Kingdom population; (2) to assess the relative efficiency of alternative monitoring pathways according to glaucoma risk; (3) to determine the clinical and cost-effectiveness of treating people with ocular hypertension with intraocular pressure of 22 or 23 mmHg and (4) to elicit patient preferences for monitoring. Design:(1) Retrospective data analysis of electronic medical records of ocular hypertension patients attending hospital eye services. The influence of the Ocular Hypertension Study-European Glaucoma Prevention Study predictors and additional ocular and systematic factors was explored. Validation: the Ocular Hypertension Study-European Glaucoma Prevention Study prediction model was applied. Update: the model was refitted by re-estimating baseline hazard and regression coefficients. (2, 3) Predictor versus standard care, with deterministic and probabilistic sensitivity analyses. Subgroup analysis for people with 22-23 mmHg intraocular pressure. (4) Discrete choice experiment. Setting and participants:People with intraocular pressure 22-32 mmHg in either eye, at least four visual field tests, 5 years of follow-up, no significant ocular comorbidities. Data sourced from secondary clinical settings. Main outcome measures:Discriminative ability (c-index) and calibration (calibration slope) to predict conversion to glaucoma in 5 years. Quality-adjusted life-years, incremental cost-effectiveness ratio, preferences. Data sources:Electronic medical records of 10 hospitals in England. Results:(1) Of 9030 patients with ocular hypertension who fitted the inclusion criteria 1530 (16.9%) converted to glaucoma. The Ocular Hypertension Study-European Glaucoma Prevention Study model provided a pooled c-index of 0.61 (95% confidence interval: 0.60 to 0.63). The updated model had a pooled c-index of 0.67 (0.51 to 0.84). (2) In the economic model almost all (99%) patients were treated in the risk predictor strategy, and less than half (47%) in the standard care strategy. The risk predictor strategy produced higher costs, but also higher quality-adjusted life-years and is likely to be cost-effective compared with standard care. (3) Patients with ocular hypertension and intraocular pressure 22-23 mmHg had similar risk of conversion to the rest of the cohort. A treat-all strategy may not be cost-effective. (4) Three hundred and sixty patients were recruited from four NHS hospitals. Almost all respondents (92%) had experienced face-to-face monitoring at a hospital; fewer respondents had experienced virtual clinics (47%) or community optometrist monitoring (43%). Most patients preferred hospital-based monitoring services by health professionals rather than community-based by optometrists but patients with prior experience of community optometrist monitoring preferred it. Patients preferred options associated with lower risk of conversion and lower costs. Limitations:Insufficient data to evaluate influence of ethnicity or ocular factors such as optic disc and retinal anatomy. Conclusions:We validated the Ocular Hypertension Study-European Glaucoma Prevention Study predictor model in a large population with ocular hypertension achieving modest improvements. The use of a risk prediction tool is likely to be cost-effective. Reducing the risk of conversion was the most important preference for patients with ocular hypertension. Future work:Future work should address the influence of genetic or other ocular factors in disease progression, evaluation of effectiveness and cost-effectiveness of different models of eye care, and on how to avoid late glaucoma presentation. Funding:This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR131808.

Abstract This study evaluated the feasibility of collecting passive and active digital phenotyping data using the OverSight iOS application in individuals with inherited retinal diseases (IRDs), and explored associations between digital behavioural markers, visual function and mental health. Participants with IRDs were recruited from Moorfields Eye Hospital (UK) and followed for 12 months. OverSight passively captures mobility data through HealthKit and typing-derived metrics through SensorKit. Participants completed patient-reported outcome measures (EQ-5D, NEI-VFQ-25, HADS and MRDQ) within the app. Passive data included step count, walking speed, typing speed, total words typed, autocorrections, and sentiment word categories (anxiety, down and health-related terms). Feasibility indices included enrolment, retention and completeness of passive datastreams. Twenty-five participants were enrolled, and 92% were retained at 12 months. Seventeen participants met the validity threshold for HealthKit data, and 16 also met SensorKit thresholds. Median daily step count was 6087, walking speed 1.18 m/s and typing speed 2.19 characters/s. Age was negatively correlated with typing speed and anxiety-related word use, and photopic peripheral visual difficulty was negatively correlated with anxiety- and down-related word use. Digital phenotyping using OverSight was feasible over 12 months. Exploratory analyses suggest mobility, typing behaviour and sentiment markers may represent useful adjunctive indicators of functional vision and psychological status. These data may support remote monitoring and earlier identification of clinically relevant changes, informing more timely personalised patient management in IRDs.

Age-related macular degeneration (AMD) is the leading cause of blindness in high income countries and third most common cause of blindness worldwide. This chapter provides an overview of existing literature pertaining to the ways in which AMD impacts clinical measures of visual function, quality of life, and performance of everyday tasks. As well as being used in clinics, some of the tests described in this chapter have the potential to be piloted in patients' homes as self-monitoring tools, or as patient-centred outcome measures in clinical trials for new treatments in AMD. Moreover, the research findings reported in this literature review should help clinicians with patient management and expectations, and should to inform future patient, public and professional education on AMD.

BACKGROUND/OBJECTIVES:This systematic literature review examines the quality of early clinical evaluation of artificial intelligence (AI) decision support systems (DSS) reported in glaucoma care. Artificial Intelligence applications within glaucoma care are increasing within the literature. For such DSS, there needs to be standardised reporting to enable faster clinical adaptation. In May 2022, a checklist to facilitate reporting of early AI studies (DECIDE-AI) was published and adopted by the EQUATOR network. METHODS:The Cochrane Library, Embase, Ovid MEDLINE, PubMed, SCOPUS, and Web of Science Core Collection were searched for studies published between January 2020 and May 2023 that reported clinical evaluation of DSS for the diagnosis of glaucoma or for identifying the progression of glaucoma driven by AI. PRISMA guidelines were followed (PROSPERO registration: CRD42023431343). Study details were extracted and were reviewed against the DECIDE-AI checklist. The AI-Specific Score, Generic-Item Score, and DECIDE-AI Score were generated. RESULTS:A total of 1,552 records were screened, with 19 studies included within the review. All studies discussed an early clinical evaluation of AI use within glaucoma care, as defined by the a priori study protocol. Overall, the DECIDE-AI adherence score was low, with authors under reporting the AI specific items (30.3%), whilst adhering well to the generic reporting items (84.7%). CONCLUSION:Overall, reporting of important aspects of AI studies was suboptimal. Encouraging editors and authors to incorporate the checklist will enhance standardised reporting, bolstering the evidence base for integrating AI DSS into glaucoma care workflows, thus help improving patient care and outcomes.

Background: A cross-sectional study was conducted at Moorfields Eye Hospital, UK, involving patients with CRB1-associated retinopathies: macular dystrophy (MD), cone-rod dystrophy (CORD), and early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA). The study aimed to evaluate CRB1-associated retinopathies using microperimetry (macular integrity assessment (S-MAIA) fast protocol) and spectral domain optical coherence tomography (SD-OCT). Methods: Data quality and participant attrition were assessed in 18 patients (10 MD, 5 EOSRD/LCA, 3 CORD), aged 10–52 years, with a median best corrected visual acuity (BCVA) of 0.41 logMAR. Results: Microperimetry and SD-OCT data were obtained from 14 and 18 patients, respectively, but eccentric fixation hindered structure-function analysis. All participants showed overall abnormal sensitivity on the S-MAIA fast protocol. Parafoveal volume was significantly increased, while foveal thickness and volume were reduced compared to normative data (p < 0.01). Conclusions: This study highlights the challenges of participant attrition and the need for alternative functional metrics to complement traditional evaluations. It also reinforces previous findings of abnormal retinal architecture in CRB1-associated retinopathies, providing further insights into S-MAIA and SD-OCT assessments for this patient population.

BACKGROUND/OBJECTIVES:Although polygenic risk scores (PRSs) have been developed for age-related macular degeneration (AMD), it is not known whether these scores are associated with impairment of visual functions in older individuals with healthy macula. We evaluated age-related changes in visual function in people aged 55 years or above with healthy macula and determined the associations of age-related visual function changes with AMD PRS in people with healthy macula. SUBJECTS/METHODS:Participants aged 55 years or above with healthy macula and a comparative group of people with early or intermediate AMD from the Northern Ireland Sensory Ageing study were included. 45 SNPs were included for PRS calculation. RESULTS:A total of 470 participants with healthy macula were included (Beckman grade 0 or 1). The comparator group consisted of participants with early AMD (n = 87) or intermediate AMD (n = 48). All visual functions except metrics of central visual field assessment showed a significant decline with age in adjusted linear regression models. Rod intercept time (RIT) was the only visual function significantly associated with PRS with Beta = 0.12 (95% confidence interval: 0.01-0.23), P = 0.03. A PRS integrated model achieved the highest area under the receiver operating characteristic curve (AUC) of 0.803 (0.732 to 0.874) to distinguish between normal or increased RIT. CONCLUSIONS AND RELEVANCE:We observed a significant decline in multiple visual functions with increasing age. However, PRS was significantly associated with RIT only, highlighting the genetic association of age-related decline in rod function.

OBJECTIVE:To validate and update the Ocular Hypertension Treatment Study-European Glaucoma Prevention Study (OHTS-EGPS) model predicting risk of conversion from ocular hypertension (OHT) to glaucoma using electronic medical records (EMR). DESIGN:Evaluation and update of a risk prediction algorithm using EMRs and linked visual field (VF) tests. PARTICIPANTS:Newly diagnosed OHT patients attending hospital glaucoma services in England. Inclusion criteria are as follows: intraocular pressure (IOP) 22 to 32 mmHg (either eye); normal baseline VF test, defined as Glaucoma Hemifield Test (GHT) "within normal range" in a reliable VF test; at least 2 VF tests in total; no significant ocular comorbidities. METHODS:Risk factors are as follows: age, ethnicity, sex, IOP, vertical cup-to-disc ratio, central corneal thickness, VF pattern standard deviation, family history of glaucoma, systemic hypertension, diabetes mellitus, and glaucoma treatment. Glaucoma conversion was defined as 2 consecutive and reliable VF tests with GHT "outside normal limits" and/or need for glaucoma surgery. For validation, the OHTS-EGPS model was applied to predict a patient's risk of developing glaucoma in 5 years. In the updating stage, the OHTS model was refitted by re-estimating the baseline hazard and regression coefficients. The updated model was cross-validated and several variants were explored. MAIN OUTCOME MEASURES:Measures of discriminative ability (c-index) and calibration (calibration slope) were calculated and pooled across hospitals using random effects meta-analysis. RESULTS:From a total of 138 461 patients from 10 hospital glaucoma services in England, 9030 patients with OHT fitted the inclusion criteria. A total of 1530 (16.9%) patients converted to glaucoma during this follow-up period. The OHTS-EGPS model provided a pooled c-index of 0.61 (95% confidence interval: 0.60-0.63), ranging from 0.55 to 0.67 between hospitals. The pooled calibration slope was 0.45 (0.38-0.51), ranging from 0.25 to 0.64 among hospitals. The overall refitted model performed better than the OHTS-EGPS model, with a pooled c-index of 0.67 (0.65-0.69), ranging from 0.65 to 0.75 between hospitals. CONCLUSIONS:We performed an external validation of the OHTS-EGPS model in a large English population. Refitting the model achieved modest improvements in performance. Given the poor performance of the OHTS-EGPS model in our population, one should use caution in its application to populations that differ from those in the OHTS and EGPS. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background: Charles Bonnet syndrome (CBS) is a condition characterised by the occurrence of vivid and complex visual hallucinations in individuals with visual impairment. Objective: To explore the relationship between emotional distress and the perceived impact of CBS symptoms on participants’ lives. We tested the hypothesis that heightened negative affect was associated with a more negative appraisal of CBS symptoms, increased self-reported loneliness, and poorer quality of life (QOL). Design: Cross-sectional. Methods: Participants recruited predominantly via vision-related charities rated their hallucinations and their impact on a Likert scale. Loneliness and negative affect were assessed with the Three-Item Loneliness Scale and Positive and Negative Affect Schedule. Health index (EQ-5D-3L) and vision-related QOL (VF-9) were also assessed. Correlation analysis and multi-variable regression determined the relation between survey responses. Results: The majority of 126 respondents (81%) were aged 65+ years and 84% reported active CBS symptoms. Fifty-five percent of respondents rated impact of CBS as negative and no-one rated the impact as ‘very pleasant’. A statistically significant correlation was found between impact of CBS and negative affect ( p ⩽ 0.001; rho = −0.34) and impact of CBS and loneliness ( p = 0.017; rho = −0.21). The relation between negative affect and CBS impact remained statistically significant when accounting for the impact of loneliness and the relationship between loneliness and CBS effect ( p = 0.002, adj R2 = 0.1). A statistically significant correlation between loneliness and negative affect ( p ⩽ 0.001; rho = 0.55) was also found. Conclusion: Respondents experiencing negative emotions were more likely to perceive the impact of CBS symptoms as negative and report greater feelings of loneliness. Negative affect is an important consideration when assessing people with CBS.

Purpose: This study aims to determine whether OCT-derived rates of change in minimum rim width (MRW) are associated with and can potentially predict corresponding alterations in retinal nerve fiber layer thickness (RNFLT) in people with glaucoma. Methods: The rates of change between six-monthly visits were taken from 568 eyes of 278 participants in the P3 Study. Structural equation models (SEM) assessed whether one parameter was predicted by the concurrent or previous rate of the other parameter, after adjusting for its own rate in the previous time interval. Root mean square error of approximation (RMSEA, with 90% confidence intervals [CI]), Tucker Lewis index (TLI) and the comparative fit index (CFI) assessed goodness of fit. Results: Models without a time lag provided a better fit for the data (RMSEA = 0.101 [CI, 0.089, 0.113]), compared to a model featuring a time lag in RNFLT (RMSEA = 0.114 [CI, 0.102, 0.126]) or MRW (RMSEA = 0.114 [CI, 0.102, 0.127]). The SEMs indicated that rates for both MRW and RNFLT were predicted by their own rate in the previous time interval and by the other measure's change in the concurrent time interval (P > 0.001 for all). No evidence of a clinically significant time lag for either parameter was determined. Conclusions: MRW and RNFLT exhibit concurrent changes over time in patients with glaucoma, with no clinically significant time lag determined. Translational Relevance: RNFLT may be more useful than MRW in early glaucoma assessment because of its previously reported lower variability and reduced sensitivity to intraocular pressure changes.

Objectives To explore the acceptability of an eHealth App for vision-related monitoring and symptom reporting among young people with a visual impairment and their parents. Methods Qualitative investigation using virtual semi-structured focus groups (via Zoom software) of seven young participants with a genetic eye disorder including inherited retinal disease and structural eye abnormalities (e.g. microphthalmia), and 7 parents; all recruited from ocular genetic clinics at Moorfields Eye Hospital. Audio transcripts were analysed using thematic analysis. Results Data were coded into six key themes: (1) increased involvement in care, (2) opportunity for less hospital-centric care, (3) better representation of visual impairment in a real-world setting, (4) trust in a reputable service provider, (5) harnessing data for health purposes and (6) intended purpose of the app. Both young people and their families were accepting of an eHealth app and felt they would be empowered by greater involvement in their care plan, if privacy of the data was retained, and information was managed correctly. While parents endorsed the opportunity for mental health tracking, young people were hesitant towards its inclusion. Conclusion In summary, there was overall acceptability of an eHealth app among young people with a visual impairment and their parents. These findings will help to maximise the effective integration of digital phenotyping when monitoring and supporting young people experiencing sight loss.

Background: Visual impairment can significantly impact an individual’s daily activities. Patients require regular monitoring, typically occurring within hospital eye services. Capacity constraints have necessitated innovative solutions to improve patient care. Existing digital solutions rely on task-based digital home monitoring such as visual acuity testing. These require active involvement from patients and do not typically offer an indication of quality of life. Digital phenotyping refers to the use of personal digital devices to quantify passive behaviour for detecting clinically significant changes in vision and act as biomarkers for disease. Its uniqueness lies in the ability to detect changes passively. The objective was to co-design an accessible smartphone app (OverSight) for the purposes of digital phenotyping in people with sight impairment. Methods: Development of OverSight included stakeholder consultations following principles of user-centred design. Apple iOS software frameworks (HealthKit, ResearchKit, and SensorKit) and a SwiftUI developer toolkit were used to enable the collection of active and passive data streams. Accessibility and usability were assessed using the System Usability Scale (SUS) and feedback following a 3-month pilot study. Consultations with patients informed the design of OverSight, including preferred survey scheduling and the relevancy of patient support resources. Results: Twenty visually impaired participants (mean age 42 ± 19 years) were recruited to the pilot study. The average score on the SUS was 76.8 (±8.9), indicating good usability. There was a statistically significant moderate negative correlation between SUS scores and visual acuity in both the better (r = −0.494; p ≤ 0.001) and worse eye (r = −0.421; p ≤ 0.001). Conclusions: OverSight offers promising potential for collecting patient-generated health data for the purposes of digital phenotyping in patients with eye disease. Through further testing and validation, this novel approach to patient care may ultimately provide opportunities for remote monitoring in ophthalmology.

Purpose: This study investigates the temporal relationship between blood flow changes and alterations in retinal nerve fiber layer thickness (RNFLT) and mean deviation (MD) in individuals with glaucoma. Methods: Blood flow, measured by mean blur rate in optic nerve head vessels (MBRv) and tissues (MBRt) using laser speckle flowgraphy (LSFG)-NAVI, was analyzed using structural equation models (SEMs). SEMs assessed whether the previous rate of one parameter predicted the current rate of the other parameter, adjusted for its own rate in the previous time interval. Data from 345 eyes of 174 participants were gathered from visits every six months. Results: Rates of change of both MBRv and MBRt were significantly predicted by their own rate in the previous time interval and by the rate of change of MD in the previous time interval (P < 0.001 and P = 0.043, respectively), but not by the rate of MD in the concurrent interval (P = 0.947 and P = 0.549), implying that changes in MD precede changes in blood flow. Rates of change of RNFLT were predicted by their own previous rate and the rate of change of MBRv and MBRt in either the previous interval (P = 0.002 and P = 0.008) or the concurrent interval (P = 0.001 and P = 0.018), suggesting that MBR may change before RNFLT. Conclusions: The evidence supports a temporal sequence where MD changes precede blood flow changes, which, in turn, may precede alterations in RNFLT.

TopicAssessing Reporting Standards in Glaucoma Studies Utilizing Electronic Health Records (EHR)Clinical RelevanceGlaucoma's significance, underscored by its status as a leading cause of irreversible blindness worldwide, necessitates reliable research findings. This study evaluates adherence to the CODE-EHR Framework in glaucoma studies using EHR, aiming to improve clinical care and patient outcomes.MethodsA systematic review, following PRISMA guidelines (PROSPERO CRD42023430025), identified relevant studies (January 2022-May 2023) in MEDLINE, EMBASE, CINAHL, and Web of Science. Eligible studies, using EHR data from clinical institutions for glaucoma research, were assessed for study design, participant characteristics, EHR data, and sources. Quality appraisal used the CODE-EHR Framework, focusing on data construction, linkage, fitness for purpose, disease and outcome definitions, analysis, and ethics and governance.ResultsOf 31 identified studies, predominant EHR sources were hospitals and clinical warehouses. Commonly reported elements included age, gender, glaucoma diagnosis, and intraocular pressure. Only 16% fully adhered to CODE-EHR Framework's minimum standards, with none meeting preferred standards. While statistical analysis and ethical considerations were relatively well-addressed, areas such as EHR data management and study design showed room for improvement. Patient and public involvement, and acknowledgment of data linkage processes, data security and storage reporting were often missed.ConclusionAdherence to CODE-EHR Framework's standards in EHR-based studies of glaucoma can be improved upon. Standardised reporting of EHR data is essential to ensure the reliability of research, facilitating its translation into clinical practice and improving healthcare decision-making for better patient outcomes.

Purpose: Mutations affecting the CRB1 gene can result in a range of retinal phenotypes, including early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa, cone-rod dystrophy (CORD), and macular dystrophy (MD). As research into treatment strategies advances towards clinical translation, there is a need to establish reliable outcome metrics. This study explores the contrast sensitivity function (CSF) across different spatial frequencies in individuals with CRB1-retinopathies using the child-friendly PopCSF test, an iPad-based "gamified" assessment. Methods: Prospective cross-sectional study of 20 patients with molecularly confirmed biallelic CRB1 pathogenic variants from Moor fields Eye Hospital, London, UK, was conducted. Best-corrected visual acuity (BCVA), contrast sensitivity using the PelliRobson chart, and the PopCSF test were performed. Results: Of the 20 CRB1 patients, seven had EOSRD/LCA, three had CORD, and 10 had MD. There was no statistically significant difference between the mean BCVA between phenotypes (P = 0.066). However, a significant difference was found between groups in the mean letter log contrast sensitivity (logCS) and area under the contrast sensitivity function (AUCSF) with P = 0.047 and P < 0.001, respectively. A moderate positive correlation was observed between Pelli-Robson and PopCSF (r = 0.53, P = 0.020). The CRB1 cohort had significantly lower CSF at both low and high spatial frequencies compared to controls. Among the CRB1 phenotypes, patients with EOSRD/LCA, exhibited the lowest CSF. Conclusions: This study is the first to examine CSF across spatial frequencies in patients with CRB1-retinopathies using the novel PopCSF test. Translational Relevance: The CSF holds promise as a potential functional vision trial endpoint.

Purpose:The purpose of this study was to assess test-retest variability and discriminatory power of measures from macular integrity assessment (S-MAIA) and AdaptDx. Methods:This is a cross-sectional study of 167 people with intermediate age-related macular degeneration (iAMD), no AMD (controls; n = 54), early AMD (n = 28), and late AMD (n = 41), recruited across 18 European ophthalmology centers. Repeat measures of mesopic and scotopic S-MAIA average (mean) threshold (MMAT decibels [dB] and SMAT [dB]) and rod intercept time (RIT [mins]) at 2 visits 14 (±7) days apart were recorded. Repeat measures were assessed by Bland-Altman analysis, intra-class correlation coefficients (ICCs) and variability ratios. Secondary analysis assessed the area under the receiver operating characteristic curves (AUC) to determine the ability to distinguish people as having no AMD, early AMD, or iAMD. Results:Data were available for 128, 131, and 103 iAMD participants for the mesopic and scotopic S-MAIA and AdaptDx, respectively. MMAT and SMAT demonstrate similar test-retest variability in iAMD (95% confidence interval [CI] ICC of 0.79-0.89 and 0.78-0.89, respectively). ICCs were worse in RIT (95% CI ICC = 0.55-0.77). All tests had equivalent AUCs (approximately 70%) distinguishing between subjects with iAMD and controls, whereas early AMD was indistinguishable from iAMD on all measures (AUC = <55%). A learning effect was not seen in these assessments under the operating procedures used. Conclusions:MMAT, SMAT, and RIT have adequate test-retest variability and are all moderately good at separating people with iAMD from controls. Translational Relevance:Expected levels of test-retest variability and discriminatory power of the AdaptDx and MAIA devices in a clinical study setting must be considered when designing future trials for people with AMD.

Higgins et al.1Higgins B.E. Montesano G. Crabb D.P. et al.Assessment of the Classification of Age-Related Macular Degeneration Severity from the Northern Ireland Sensory Ageing Study Using a Measure of Dark Adaptation.Ophthalmology Science. 2022; 2https://doi.org/10.1016/j.xops.2022.100204Abstract Full Text Full Text PDF Scopus (0) Google Scholar use rod intercept time (RIT), a measure of rod-mediated dark adaptation (RMDA), to compare older adults in different stages of age-related macular degeneration (AMD). There are some statistical issues in this presentation that merit commentary. As implied by the name of the disease, the incidence and severity of age-related macular degeneration increases with age. With RMDA being such a closely related psychophysical measure to the pathophysiology of AMD, it is not surprising that age is a confounder when analyzing RMDA and disease severity. Thus, it is important to design studies and analyze data which correctly mitigate these effects (Szklo and Neito2Szklo M, Nieto FJ. Epidemiology, Beyond the Basics. 3 ed. Jones and Bartlett Learning; 2014.Google Scholar is one of many texts which explore confounding and mitigation approaches in-depth). Higgins et al. state in the abstract that the main outcome measure in their study is age-corrected RIT. However, as stated in the methods, age was included as a covariable in parametric survival models. Therefore, the hazard rate of rod intercept in their article was adjusted for age, but RIT itself was not corrected for age. Furthermore, their interpretation of the results based on the parametric survival model is questionable. For example, they state that RMDA was significantly slower in Beckman grade 3 (intermediate AMD) as compared to the other Beckman groups with less severe AMD. However, the correct interpretation of this finding is that those with Beckman grade 3 have a lower hazard rate of rod intercept compared to each of the other Beckman groups, meaning the instantaneous probability of reaching rod intercept following photobleach was lower for Beckman grade 3 compared to the other disease categories. A comparison of the hazard rate of rod intercept by disease category is not the same as comparing mean or median RIT by disease category, as the former compares the probability of the event over time while the latter compares a measured value. Higgins et al. state, “. . . [A]nother strength of our methodology was that we compensated for age effects. For example, a previous study by Owsley et al.3Owsley C. Huisingh C. Clark M.E. Jackson G.R. McGwin Jr., G. Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.Curr Eye Res. 2016; 41: 266-272https://doi.org/10.3109/02713683.2015.1011282Crossref PubMed Scopus (59) Google Scholar,4Owsley C. Huisingh C. Jackson G.R. et al.Associations between abnormal rod-mediated dark adaptation and health and functioning in older adults with normal macular health.Investigative ophthalmology & visual science. May 22 2014; 55: 4776-4789https://doi.org/10.1167/iovs.14-14502Crossref Scopus (56) Google Scholar did not correct the estimates of RIT but rather applied a correction for age and other factors to the estimated odds ratios of having an abnormal RIT based on predefined cutoffs.” Contrary to their claim, adjusting measures of association such as odds ratios for a confounder, in this case age, does adjust the association for it in the analysis.2Szklo M, Nieto FJ. Epidemiology, Beyond the Basics. 3 ed. Jones and Bartlett Learning; 2014.Google Scholar The models used by Owsley et al.3Owsley C. Huisingh C. Clark M.E. Jackson G.R. McGwin Jr., G. Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.Curr Eye Res. 2016; 41: 266-272https://doi.org/10.3109/02713683.2015.1011282Crossref PubMed Scopus (59) Google Scholar,4Owsley C. Huisingh C. Jackson G.R. et al.Associations between abnormal rod-mediated dark adaptation and health and functioning in older adults with normal macular health.Investigative ophthalmology & visual science. May 22 2014; 55: 4776-4789https://doi.org/10.1167/iovs.14-14502Crossref Scopus (56) Google Scholar to calculate the odds ratios included age as a covariable just like Higgins et al. did in their parametric survival models. Additionally, creating an outcome measure like odds ratios based on impaired and unimpaired RIT is a valid approach if it addresses the question(s) of interest. Statements by Higgins et al. that their own analyses are more appropriate since they corrected RIT directly for age are misplaced, not only because they never age-corrected RIT but also since the outcome measures in their analysis and the Owsley et al. analyses assessed different research questions. The use of survival models to analyze RIT should be done cautiously. Methods used should directly address the research question of interest, and interpretations must accurately reflect the statistical assessment completed. Response to the letter by Swain et al.Ophthalmology SciencePreviewWe thank Swain et al. for their interest in our work1 and for the chance to address some perceived statistical issues. Their main criticism pertains to our use of parametric survival analysis to estimate the parameters of a model describing changes in Rod intercept time (RIT) due to age and disease stage, which they define ‘questionable’. In their ‘correct’ interpretation of the results, they explain how our model describes the changes in the hazard rate of reaching the rod intercept among groups. Full-Text PDF Open Access