Defining the learning curve for robotic pancreaticoduodenectomy for a single surgeon following experience with laparoscopic pancreaticoduodenectomy.

Robotic pancreaticoduodenectomy (RPD) has a learning curve of approximately 30-250 cases to reach proficiency. The learning curve for laparoscopic pancreaticoduodenectomy (LPD) at Duke University was previously defined as 50 cases. This study describes the RPD learning curve for a single surgeon following experience with LPD. LPD and RPD were retrospectively analyzed. Continuous pathologic and perioperative metrics were compared and learning curve were defined with respect to operative time using CUSUM analysis. Seventeen LPD and 69 RPD were analyzed LPD had an inverted learning curve possibly accounting for proficiency attained during the surgeon's fellowship and acquisition of new skills coinciding with more complex patient selection. The learning curve for RPD had three phases: accelerated early experience (cases 1-10), skill consolidation (cases 11-40), and improvement (cases 41-69), marked by reduction in operative time. Compared to LPD, RPD had shorter operative time (379 vs 479 min, p < 0.005), less EBL (250 vs 500, p < 0.02), and similar R0 resection. RPD also had improved LOS (7 vs 10 days, p < 0.007), and lower rates of surgical site infection (10% vs 47%, p < 0.002), DGE (19% vs 47%, p < 0.03), and readmission (13% vs 41%, p < 0.02). Experience in LPD may shorten the learning curve for RPD. The gap in surgical quality and perioperative outcomes between LPD and RPD will likely widen as exposure to robotics in General Surgery, Hepatopancreaticobiliary, and Surgical Oncology training programs increase.

Performance of Linear Mixed Models in Estimating Structural Rates of Glaucoma Progression Using Varied Random Effect Distributions.

Purpose: To compare how linear mixed models (LMMs) using Gaussian, Student t, and log-gamma (LG) random effect distributions estimate rates of structural loss in a glaucomatous population using OCT and to compare model performance to ordinary least squares (OLS) regression. Design: Retrospective cohort study. Subjects: Patients in the Bascom Palmer Glaucoma Repository (BPGR). Methods: Eyes with ≥ 5 reliable peripapillary retinal nerve fiber layer (RNFL) OCT tests over ≥ 2 years were identified from the BPGR. Retinal nerve fiber layer thickness values from each reliable test (signal strength ≥ 7/10) and associated time points were collected. Data were modeled using OLS regression as well as LMMs using different random effect distributions. Predictive modeling involved constructing LMMs with (n - 1) tests to predict the RNFL thickness of subsequent tests. A total of 1200 simulated eyes of different baseline RNFL thickness values and progression rates were developed to evaluate the likelihood of declared progression and predicted rates. Main Outcome Measures: Model fit assessed by Watanabe-Akaike information criterion (WAIC) and mean absolute error (MAE) when predicting future RNFL thickness values; log-rank test and median time to progression with simulated eyes. Results: A total of 35 862 OCT scans from 5766 eyes of 3491 subjects were included. The mean follow-up period was 7.0 ± 2.3 years, with an average of 6.2 ± 1.4 tests per eye. The Student t model produced the lowest WAIC. In predictive models, all LMMs demonstrated a significant reduction in MAE when estimating future RNFL thickness values compared with OLS (P < 0.001). Gaussian and Student t models were similar and significantly better than the LG model in estimating future RNFL thickness values (P < 0.001). Simulated eyes confirmed LMM performance in declaring progression sooner than OLS regression among moderate and fast progressors (P < 0.01). Conclusions: LMMs outperformed conventional approaches for estimating rates of OCT RNFL thickness loss in a glaucomatous population. The Student t model provides the best model fit for estimating rates of change in RNFL thickness, although the use of the Gaussian or Student t distribution in models led to similar improvements in accurately estimating RNFL loss. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intraocular Pressure and Rates of Macular Thinning in Glaucoma.

PURPOSE: To evaluate the effect of intraocular pressure (IOP) on the rates of macular thickness (ganglion cell layer [GCL] and ganglion cell-inner plexiform layer [GCIPL]) change over time measured by spectral-domain (SD) OCT. DESIGN: Retrospective cohort study. PARTICIPANTS: Overall, 451 eyes of 256 patients with primary open-angle glaucoma. METHODS: Data were extracted from the Duke Ophthalmic Registry, a database of electronic medical records of patients observed under routine clinical care at the Duke Eye Center, and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality Spectralis SD-OCT macula scans were included. Linear mixed models were used to investigate the relationship between average IOP during follow-up and rates of GCL and GCIPL thickness change over time. MAIN OUTCOME MEASURES: The effect of IOP on the rates of GCL and GCIPL thickness loss measured by SD-OCT. RESULTS: Eyes had a mean follow-up of 1.8 ± 1.3 years, ranging from 0.5 to 10.2 years. The average rate of change for GCL thickness was -0.220 µm/year (95% confidence interval [CI], -0.268 to -0.172 µm/year) and for GCIPL thickness was -0.231 µm/year (95% CI, -0.302 to -0.160 µm/year). Each 1-mmHg higher mean IOP during follow-up was associated with an additional loss of -0.021 µm/year of GCL thickness (P = 0.001) and -0.032 µm/year of GCIPL thickness (P = 0.001) after adjusting for potentially confounding factors, such as baseline age, disease severity, sex, race, central corneal thickness, and follow-up time. CONCLUSIONS: Higher IOP was significantly associated with faster rates of GCL and GCIPL loss over time measured by SD-OCT, even during relatively short follow-up times. These findings support the use of SD-OCT GCL and GCIPL thickness measurements as structural biomarkers for the evaluation of the efficacy of IOP-lowering therapies in slowing down the progression of glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

mHealth Coping Skills Training for Symptom Management (mCOPE) for colorectal cancer patients in early to mid-adulthood: Study protocol for a randomized controlled trial.

Background: Colorectal cancer (CRC) patients in early to mid-adulthood (≤50 years) are challenged by high symptom burden (i.e., pain, fatigue, distress) and age-related stressors (e.g., managing family, work). Cognitive behavioral theory (CBT)-based coping skills training interventions reduce symptoms and improve quality of life in cancer patients. However, traditional CBT-based interventions are not accessible to these patients (e.g., in-person sessions, during work day), nor designed to address symptoms within the context of this stage of life. We developed a mobile health (mHealth) coping skills training program for pain, fatigue and distress (mCOPE) for CRC patients in early to mid-adulthood. We utilize a randomized controlled trial to test the extent to which mCOPE reduces pain, fatigue and distress (multiple primary outcomes) and improves quality of life and symptom self-efficacy (secondary outcomes). Methods/Design: Patients (N = 160) ≤50 years with CRC endorsing pain, fatigue and/or distress are randomized 1:1 to mCOPE or standard care. mCOPE is a five-session CBT-based coping skills training program (e.g., relaxation, activity pacing, cognitive restructuring) that was adapted for CRC patients in early to mid-adulthood. mCOPE utilizes mHealth technology (e.g., videoconference, mobile app) to deliver coping skills training, capture symptom and skills use data, and provide personalized support and feedback. Self-report assessments are completed at baseline, post-treatment (5-8 weeks post-baseline; primary endpoint), and 3- and 6-months later. Conclusions: mCOPE is innovative and potentially impactful for CRC patients in early to mid-adulthood. Hypothesis confirmation would demonstrate initial efficacy of a mHealth cognitive behavioral intervention to reduce symptom burden in younger CRC patients.

Predictive Value of Early Autism Detection Models Based on Electronic Health Record Data Collected Before Age 1 Year.

Importance: Autism detection early in childhood is critical to ensure that autistic children and their families have access to early behavioral support. Early correlates of autism documented in electronic health records (EHRs) during routine care could allow passive, predictive model-based monitoring to improve the accuracy of early detection. Objective: To quantify the predictive value of early autism detection models based on EHR data collected before age 1 year. Design, Setting, and Participants: This retrospective diagnostic study used EHR data from children seen within the Duke University Health System before age 30 days between January 2006 and December 2020. These data were used to train and evaluate L2-regularized Cox proportional hazards models predicting later autism diagnosis based on data collected from birth up to the time of prediction (ages 30-360 days). Statistical analyses were performed between August 1, 2020, and April 1, 2022. Main Outcomes and Measures: Prediction performance was quantified in terms of sensitivity, specificity, and positive predictive value (PPV) at clinically relevant model operating thresholds. Results: Data from 45 080 children, including 924 (1.5%) meeting autism criteria, were included in this study. Model-based autism detection at age 30 days achieved 45.5% sensitivity and 23.0% PPV at 90.0% specificity. Detection by age 360 days achieved 59.8% sensitivity and 17.6% PPV at 81.5% specificity and 38.8% sensitivity and 31.0% PPV at 94.3% specificity. Conclusions and Relevance: In this diagnostic study of an autism screening test, EHR-based autism detection achieved clinically meaningful accuracy by age 30 days, improving by age 1 year. This automated approach could be integrated with caregiver surveys to improve the accuracy of early autism screening.

Identifying Risk Factors for Blindness From Glaucoma at First Presentation to a Tertiary Clinic.

PURPOSE: Glaucoma is the leading cause of irreversible blindness, a crippling disability resulting in higher risks of chronic health conditions. To better understand disparities in blindness risk, we identified risk factors of blindness on first presentation to a glaucoma clinic using a large clinical database. DESIGN: Retrospective cross-sectional study. METHODS: We used electronic health records of glaucoma patients from the Duke Ophthalmic Registry. International Classification of Diseases codes were used to identify glaucoma and exclude concurrent diseases. Blindness classification was based on the definition of legal blindness. Risk factors included gender, race, marital status, age, intraocular pressure, diabetes history, income level, and education. Odds ratios (ORs) and 95% CIs were calculated for risk factors using univariable and multivariable logistic regression. RESULTS: Our cohort consisted of 3753 patients, with 192 (5%) blind on first presentation. In univariable models, African American / Black race (OR 2.48, 95% CI 1.83-3.36), single marital status (1.74, 95% CI 1.25-2.44), prior diabetes diagnosis (2.23, 95% CI 1.52-3.27), and higher intraocular pressure (1.29 per 1 SD higher, 95% CI 1.13-1.46) were associated with increased risk of presenting blind, whereas higher annual income (0.75, 95% CI 0.65-0.86) and education (0.77, 95% CI 0.69-0.85) were associated with lower risk. These associations remained significant and in the same direction in a multivariable model apart from income, which became insignificant. CONCLUSIONS: Using a large real-world clinical database, we identified risk factors associated with presentation with blindness among glaucoma patients. Our results highlight disparities in health care outcomes and indicate the importance of targeted education to reduce disparities in blindness.

A Framework for Automating Psychiatric Distress Screening in Ophthalmology Clinics Using an EHR-Derived AI Algorithm.

Purpose: In patients with ophthalmic disorders, psychosocial risk factors play an important role in morbidity and mortality. Proper and early psychiatric screening can result in prompt intervention and mitigate its impact. Because screening is resource intensive, we developed a framework for automating screening using an electronic health record (EHR)-derived artificial intelligence (AI) algorithm. Methods: Subjects came from the Duke Ophthalmic Registry, a retrospective EHR database for the Duke Eye Center. Inclusion criteria included at least two encounters and a minimum of 1 year of follow-up. Presence of distress was defined at the encounter level using a computable phenotype. Risk factors included available EHR history. At each encounter, risk factors were used to discriminate psychiatric status. Model performance was evaluated using area under the receiver operating characteristic (ROC) curve and area under the precision-recall curve (PR AUC). Variable importance was presented using odds ratios (ORs). Results: Our cohort included 358,135 encounters from 40,326 patients with an average of nine encounters per patient over 4 years. The ROC and PR AUC were 0.91 and 0.55, respectively. Of the top 25 predictors, the majority were related to existing distress, but some indicated stressful conditions, including chemotherapy (OR = 1.36), esophageal disorders (OR = 1.31), central pain syndrome (OR = 1.25), and headaches (OR = 1.24). Conclusions: Psychiatric distress in ophthalmology patients can be monitored passively using an AI algorithm trained on existing EHR data. Translational Relevance: When paired with an effective referral and treatment program, such algorithms may improve health outcomes in ophthalmology.

Rates of Glaucoma Progression Derived from Linear Mixed Models Using Varied Random Effect Distributions.

PURPOSE: To compare the ability of linear mixed models with different random effect distributions to estimate rates of visual field loss in glaucoma patients. METHODS: Eyes with five or more reliable standard automated perimetry (SAP) tests were identified from the Duke Glaucoma Registry. Mean deviation (MD) values from each visual field and associated timepoints were collected. These data were modeled using ordinary least square (OLS) regression and linear mixed models using the Gaussian, Student's t, or log-gamma (LG) distributions as the prior distribution for random effects. Model fit was compared using the Watanabe-Akaike information criterion (WAIC). Simulated eyes of varying initial disease severity and rates of progression were created to assess the accuracy of each model in predicting the rate of change and likelihood of declaring progression. RESULTS: A total of 52,900 visual fields from 6558 eyes of 3981 subjects were included. Mean follow-up period was 8.7 ± 4.0 years, with an average of 8.1 ± 3.7 visual fields per eye. The LG model produced the lowest WAIC, demonstrating optimal model fit. In simulations, the LG model declared progression earlier than OLS (P < 0.001) and had the greatest accuracy in predicted slopes (P < 0.001). The Gaussian model significantly underestimated rates of progression among fast and catastrophic progressors. CONCLUSIONS: Linear mixed models using the LG distribution outperformed conventional approaches for estimating rates of SAP MD loss in a population with glaucoma. TRANSLATIONAL RELEVANCE: Use of the LG distribution in models estimating rates of change among glaucoma patients may improve their accuracy in rapidly identifying progressors at high risk for vision loss.

Atrial branch coronary artery stenosis as a mechanism for atrial fibrillation.

BACKGROUND: The etiology of atrial fibrillation (AF) is multifactorial and incompletely understood. OBJECTIVE: The purpose of this study was to evaluate the association between coronary artery disease (CAD) affecting atrial tissue and AF. METHODS: Patients from a single center with obstructive CAD during cardiac catheterization (January 1, 2007, through December 1, 2013) were included in a matched case-control analysis on the basis of the presence or absence of new-onset AF within 12 months of catheterization. Quantitative measurements of stenosis severity were performed for the sinoatrial nodal artery, atrioventricular (AV) nodal artery, and right intermediate atrial artery (RIAA) as well as the right coronary, left circumflex, and left anterior descending proximal to the takeoff for each atrial level artery. A multivariable logistic regression model identified factors associated with AF. RESULTS: Of 1794 patients, 115 (6%) developed AF within 1 year of catheterization. The matched cohort included 110 patients with and 110 patients without AF within 12 months of catheterization. Higher odds of AF at 1 year were associated with increasing lesion stenosis severity in the RIAA (odds ratio [OR] 1.41 per 10% increase in lesion severity above 50%; 95% confidence interval [CI] 1.01-1.97; P = .047) and AV nodal artery (OR 1.58 per 10% increase in lesion severity above 50%; 95% CI 1.00-2.49; P = .050). Odds of AF diagnosis during the year after catheterization increased with the number of atrial arteries with >50% lesion (OR 1.53 for each additional artery; 95% CI 1.08-2.15; P = .015). CONCLUSION: In patients with obstructive CAD, disease of the AV nodal artery and RIAA as well as a higher burden of CAD within all arteries supplying blood flow to the atrial myocardium were associated with higher odds of new-onset AF at 1 year.

Blood Pressure and Glaucomatous Progression in a Large Clinical Population.

PURPOSE: To investigate the effect of systemic arterial blood pressure (BP) on rates of progressive structural damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 7501 eyes of 3976 subjects with glaucoma or suspected of glaucoma followed over time from the Duke Glaucoma Registry. METHODS: Linear mixed models were used to investigate the effects of BP on the rates of retinal nerve fiber layer (RNFL) loss from spectral-domain OCT (SD-OCT) over time. Models were adjusted for intraocular pressure (IOP), gender, race, diagnosis, central corneal thickness (CCT), follow-up time, and baseline disease severity. MAIN OUTCOME MEASURE: Effect of mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) on rates of RNFL loss over time. RESULTS: A total of 157 291 BP visits, 45 408 IOP visits, and 30 238 SD-OCT visits were included. Mean rate of RNFL change was -0.70 µm/year (95% confidence interval, -0.72 to -0.67 µm/year). In univariable models, MAP, SAP, and DAP during follow-up were not significantly associated with rates of RNFL loss. However, when adjusted for mean IOP during follow-up, each 10 mmHg reduction in mean MAP (-0.06 µm/year; P = 0.007) and mean DAP (-0.08 µm/year; P < 0.001) but not SAP (-0.01 µm/year; P = 0.355) was associated with significantly faster rates of RNFL thickness change over time. The effect of the arterial pressure metrics remained significant after additional adjustment for baseline age, diagnosis, sex, race, follow-up time, disease severity, and corneal thickness. CONCLUSIONS: When adjusted for IOP, lower MAP and DAP during follow-up were significantly associated with faster rates of RNFL loss, suggesting that levels of systemic BP may be a significant factor in glaucoma progression.

A Community Partnership to House and Care for Complex Patients with Unstable Housing.

Rising homelessness, especially among older adults, has significant ramifications for our health care system. People experiencing homelessness tend to experience worse health and poorer access to needed health care than people with stable housing. Commonwealth Care Alliance (CCA), a not-for-profit payer and provider that offers health plans to people dually eligible for Medicare and Medicaid, sought to address homelessness among its beneficiaries through a partnership with a local community-based housing organization, Hearth. This partnership led to many CCA members gaining access to permanent supportive housing in a setting in which CCA and Hearth could monitor and address their medical, social, and behavioral needs. It also provided an opportunity to examine health care utilization and cost trends associated with permanent supportive housing. Our experience demonstrates that a community-based partnership can effectively address homelessness among older adults with significant medical needs and may be associated with reduced health care expenditures.

Rapid initial OCT RNFL thinning is predictive of faster visual field loss during extended follow-up in glaucoma.

PURPOSE: To investigate the relationship between the rate of retinal nerve fiber layer (RNFL) loss during initial follow-up and the magnitude of associated visual field loss during an extended follow-up period. DESIGN: Retrospective cohort study. METHODS: A total of 1,150 eyes of 839 glaucoma patients extracted from the Duke Glaucoma Registry. Rates of RNFL loss were obtained from global RNFL thickness values of the first 5 optical coherence tomography (OCT) scans. Rates of visual field loss were assessed using standard automated perimetry mean deviation (SAP MD) during the entire follow-up period. Joint longitudinal mixed effects models were used to estimate rates of change. Eyes were categorized as fast, moderate or slow progressors based on rates of RNFL loss, with cutoffs of ≤-2 µm/year, -2 to -1 µm/year and ≥-1 µm/year, respectively. Univariable and multivariable regressions were completed to identify significant predictors of SAP MD loss. RESULTS: The rate of RNFL change was -0.76±0.85 µm/y during initial follow-up, which occurred over 3.7±1.5 years. 765 (66%) eyes were slow, 328 (29%) moderate, and 57 (5%) fast progressors, with rates of RNFL thinning of -0.36±0.54 µm/year, -1.34±0.25 µm/year, and -2.87±1.39 µm/year respectively. The rates of SAP MD loss among slow, moderate, and fast OCT progressors were -0.16±0.35 dB/y, -0.32±0.43 dB/y, and -0.71±0.65 dB/y respectively over the extended follow-up period of 6.1±1.9 years (P<0.001). Age, OCT progressor group, and concurrent SAP rate were all significantly associated with the overall rate of SAP MD loss in a multivariable model (all P<0.001). CONCLUSION: Rapid RNFL thinning during an initial follow-up period was predictive of concurrent and subsequent rates of visual field decline over an extended period.

Comparative effectiveness of oral anticoagulants in everyday practice.

OBJECTIVES: This study evaluated the comparative effectiveness of vitamin K antagonists (VKAs), direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaI) in patients with atrial fibrillation (AF) at risk of stroke in everyday practice. METHODS: Data from patients with AF and Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category (CHA2DS2-VASc) score ≥2 (excluding gender) in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation registry were analysed using an improved method of propensity weighting, overlap weights and Cox proportional hazards models. RESULTS: All-cause mortality, non-haemorrhagic stroke/systemic embolism (SE) and major bleeding over 2 years were compared in 25 551 patients, 7162 (28.0%) not treated with oral anticoagulant (OAC) and 18 389 (72.0%) treated with OAC (FXaI (41.8%), DTI (11.4%) and VKA (46.8%)). OAC treatment compared with no OAC treatment was associated with decreased risk of all-cause mortality (HR 0.82 (95% CI 0.74 to 0.91)) and non-haemorrhagic stroke/SE (HR 0.71 (95% CI 0.57 to 0.88)) but increased risk of major bleeding (HR 1.46 (95% CI 1.15 to 1.86)). Non-vitamin K antagonist oral anticoagulant (NOAC) use compared with no OAC treatment was associated with lower risks of all-cause mortality and non-haemorrhagic stroke/SE (HR 0.67 (95% CI 0.59 to 0.77)) and 0.65 (95% CI 0.50 to 0.86)) respectively, with no increase in major bleeding (HR 1.10 (95% CI 0.82 to 1.47)). NOAC use compared with VKA use was associated with lower risk of all-cause mortality and major bleeding (rates/100 patient-years 3.6 (95% CI 3.3 to 3.9) vs 4.8 (95% CI 4.5 to 5.2) and 1.0 (95% CI 0.9 to 1.1) vs 1.4 (95% CI 1.2 to 1.6); HR 0.79 (95% CI 0.70 to 0.89) and 0.77 (95% CI 0.61 to 0.98) respectively), with similar risk of non-haemorrhagic stroke/SE (rates/100 patient-years 0.8 (95% CI 0.7 to 0.9) versus 1.0 (95% CI 0.8 to 1.1); HR 0.96 (95% CI 0.73 to 1.25). CONCLUSION: Important benefits in terms of mortality and major bleeding were observed with NOAC versus VKA with no difference among NOAC subtypes. TRIAL REGISTRATION NUMBER: NCT01090362.

An objective structural and functional reference standard in glaucoma.

The current lack of consensus for diagnosing glaucoma makes it difficult to develop diagnostic tests derived from deep learning (DL) algorithms. In the present study, we propose an objective definition of glaucomatous optic neuropathy (GON) using clearly defined parameters from optical coherence tomography and standard automated perimetry. We then use the proposed objective definition as reference standard to develop a DL algorithm to detect GON on fundus photos. A DL algorithm was trained to detect GON on fundus photos, using the proposed objective definition as reference standard. The performance was evaluated on an independent test sample with sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and likelihood ratios (LR). The test sample had 2118 fundus photos from 585 eyes of 405 individuals. The AUC to discriminate between GON and normal was 0.92 with sensitivity of 77% at 95% specificity. LRs indicated that the DL algorithm provided large changes in the post-test probability of disease for the majority of eyes. A DL algorithm to evaluate fundus photos had high performance to discriminate GON from normal. The newly proposed objective definition of GON used as reference standard may increase the comparability of diagnostic studies of glaucoma across devices and populations.

Rates of Glaucomatous Structural and Functional Change From a Large Clinical Population: The Duke Glaucoma Registry Study.

PURPOSE: To investigate rates of structural and functional change in a large clinical population of glaucoma and glaucoma suspect patients. DESIGN: Retrospective cohort. METHODS: Twenty-nine thousand five hundred forty-eight spectral-domain optical coherence tomography (OCT) and 19,812 standard automated perimetry (SAP) tests from 6138 eyes of 3669 patients with ≥6 months of follow-up, 2 good quality spectral-domain OCT peripapillary retinal nerve fiber layer scans, and 2 reliable SAP tests were included. Data were extracted from the Duke Glaucoma Registry, a large database of electronic health records of patients from the Duke Eye Center and satellite clinics. Rates of change for the 2 metrics were obtained using linear mixed models, categorized according to pre-established cutoffs, and analyzed according to the severity of the disease. RESULTS: Average rates of change were -0.73 ± 0.80 µm per year for global retinal nerve fiber layer thickness and -0.09 ± 0.36 dB per year for SAP mean deviation. More than one quarter (26.6%) of eyes were classified as having at least a moderate rate of change by spectral-domain OCT vs 9.1% by SAP (P < .001). In eyes with severe disease, 31.6% were classified as progressing at moderate or faster rates by SAP vs 26.5% by spectral-domain OCT (P = .055). Most eyes classified as fast by spectral-domain OCT were classified as slow by SAP and vice versa. CONCLUSION: Although most patients under routine care had slow rates of progression, a substantial proportion had rates that could potentially result in major losses if sustained over time. Both structural and functional tests should be used to monitor glaucoma, and spectral-domain OCT still has a relevant role in detecting fast progressors in advanced disease.

Effect of Diabetes Control on Rates of Structural and Functional Loss in Patients with Glaucoma.

PURPOSE: To investigate the association between levels of diabetes mellitus (DM) control and rates of visual field and retinal nerve fiber layer (RNFL) loss over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 351 eyes of 222 patients with type 2 DM with concomitant primary open-angle glaucoma (POAG) or suspected glaucoma extracted from the Duke Glaucoma Registry. METHODS: All patients had at least 2 reliable standard automated perimetry (SAP) tests, 2 spectral domain OCT (SD-OCT) tests, and 2 glycated hemoglobin (HbA1c) measures over time with a minimum follow-up of 6 months. Values of HbA1c were summarized for each patient as mean, peak, and fluctuation across time. Multivariable linear mixed models were used to estimate the effect of HbA1c on rates of change in SAP mean deviation (MD) and OCT RNFL thickness loss over time while adjusting for various confounding factors. MAIN OUTCOME MEASURES: Rates of change in MD and RNFL thickness over time. RESULTS: Subjects had a mean baseline age of 62.5 ± 10.2 years and follow-up time of 6.9 ± 5.1 years. Subjects had an average of 4.8 SAP tests (range, 2-28), 3.6 SD-OCT tests (range, 2-10), and 8.3 HbA1c tests (range, 2-21). Average HbA1c mean was 7.1% ± 1.1% (range, 5.4-11.7), peak HbA1c over time was 8.1% ± 2% (range, 5.5-15.6), and HbA1c fluctuation was 0.6% ± 0.6% (range, 0-4.4). Mean rate of SAP MD change was -0.09 ± 0.20 decibel/year (median -0.06 decibel/year; interquartile range -0.15 to 0.01 decibel/year), and mean rate of RNFL change was -0.83 ± 0.51 µm/year (median -0.76 µm/year; interquartile range -1.06 to 0.56 µm/year). After adjustment for confounding factors, mean, peak, and fluctuation in HbA1c levels were not significantly associated with rates of MD change over time (P = 0.994, P = 0.689, P = 0.920, respectively), nor were rates of change in RNFL loss over time (P = 0.805, P = 0.575, P = 0.770). CONCLUSIONS: We did not find a significant association between diabetes control, as measured by levels of HbA1c, and rates of visual field or RNFL loss over time in individuals with glaucoma or suspected glaucoma.

Impact of Intraocular Pressure Control on Rates of Retinal Nerve Fiber Layer Loss in a Large Clinical Population.

PURPOSE: To investigate the impact of intraocular pressure (IOP) control on rates of change of spectral-domain OCT (SD-OCT) retinal nerve fiber layer (RNFL) thickness in a large clinical population. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 85 835 IOP measurements and 60 223 SD-OCT tests from 14 790 eyes of 7844 patients. METHODS: Data were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients with glaucoma and suspected disease followed over time at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality SD-OCT scans and 2 clinical visits with Goldmann applanation tonometry were included. Eyes were categorized according to the frequency of visits with IOP below cutoffs of 21 mmHg, 18 mmHg, and 15 mmHg over time. Rates of change for global RNFL thickness were obtained using linear mixed models and classified as slow if change was slower than -1.0 µm/year; moderate if between -1.0 and -2.0 µm/year; and fast if faster than -2.0 µm/year. Multivariable models were adjusted for age, gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity. MAIN OUTCOME MEASURES: Rates of change in SD-OCT RNFL thickness according to levels of IOP control. RESULTS: Eyes had a mean follow-up of 3.5±1.9 years. Average rate of change in RNFL thickness was -0.68±0.59 µm/year. Each 1 mmHg higher mean IOP was associated with 0.05 µm/year faster RNFL loss (P < 0.001) after adjustment for potentially confounding variables. For eyes that had fast progression, 41% of them had IOP <21 mmHg in all visits during follow-up, whereas 20% of them had all visits with IOP <18 mmHg, but only 9% of them had all visits with IOP <15 mmHg. CONCLUSIONS: Intraocular pressure was significantly associated with rates of progressive RNFL loss in a large clinical population. Eyes with stricter IOP control over follow-up visits had a smaller chance of exhibiting fast deterioration. Our findings may assist clinicians in establishing target pressures in clinical practice.

The Effect of Age on Increasing Susceptibility to Retinal Nerve Fiber Layer Loss in Glaucoma.

Purpose: To determine whether aging modifies the effect of intraocular pressure (IOP) on progressive glaucomatous retinal nerve fiber layer (RNFL) thinning over time. Methods: This was a retrospective cohort study involving patients with glaucoma or suspected of having glaucoma who were followed over time from the Duke Glaucoma Registry. Rates of RNFL loss from spectral-domain optical coherence tomography (SD-OCT) were used to assess disease progression. Generalized estimating equations with robust sandwich variance estimators were used to investigate the effects of the interaction of age at baseline and mean IOP on rates of RNFL loss over time. Models were adjusted for gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity. Results: The study included 85,475 IOP measurements and 60,026 SD-OCT tests of 14,739 eyes of 7814 patients. Eyes had a mean follow-up time of 3.5 ± 1.9 years. The average rate of change in RNFL thickness was -0.70 µm/year (95% confidence interval, -0.72 to -0.67). There was a significant interaction between age and mean IOP and the rate of RNFL loss (P = 0.001), with older eyes having significantly faster rates of RNFL loss than younger ones for the same level of IOP. The effect of IOP on rates of change was greater in the inferior and superior regions of the optic disc. Conclusions: Age is a significant modifier of the relationship between IOP and glaucomatous loss in RNFL thickness over time. Older patients may be more susceptible to glaucomatous progression than younger patients at the same level of IOP.

Health system utilization before age 1 among children later diagnosed with autism or ADHD.

Children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) have 2-3 times increased healthcare utilization and annual costs once diagnosed, but little is known about their utilization patterns early in life. Quantifying their early health system utilization could uncover condition-specific health trajectories to facilitate earlier detection and intervention. Patients born 10/1/2006-10/1/2016 with ≥ 2 well-child visits within the Duke University Health System before age 1 were grouped as ASD, ADHD, ASD + ADHD, or No Diagnosis using retrospective billing codes. An additional comparison group was defined by later upper respiratory infection diagnosis. Adjusted odds ratios (AOR) for hospital admissions, procedures, emergency department (ED) visits, and outpatient clinic encounters before age 1 were compared between groups via logistic regression models. Length of hospital encounters were compared between groups via Mann-Whitney U test. In total, 29,929 patients met study criteria (ASD N = 343; ADHD N = 1175; ASD + ADHD N = 140). ASD was associated with increased procedures (AOR = 1.5, p < 0.001), including intubation and ventilation (AOR = 2.4, p < 0.001); and outpatient specialty care, including physical therapy (AOR = 3.5, p < 0.001) and ophthalmology (AOR = 3.1, p < 0.001). ADHD was associated with increased procedures (AOR = 1.41, p < 0.001), including blood transfusion (AOR = 4.7, p < 0.001); hospital admission (AOR = 1.60, p < 0.001); and ED visits (AOR = 1.58, p < 0.001). Median length of stay was increased after birth in ASD (+ 6.5 h, p < 0.001) and ADHD (+ 3.8 h, p < 0.001), and after non-birth admission in ADHD (+ 1.1 d, p < 0.001) and ASD + ADHD (+ 2.4 d, p = 0.003). Each condition was associated with increased health system utilization and distinctive patterns of utilization before age 1. Recognizing these patterns may contribute to earlier detection and intervention.

Artificial Intelligence Mapping of Structure to Function in Glaucoma.

Purpose: To develop an artificial intelligence (AI)-based structure-function (SF) map relating retinal nerve fiber layer (RNFL) damage on spectral domain optical coherence tomography (SDOCT) to functional loss on standard automated perimetry (SAP). Methods: The study included 26,499 pairs of SAP and SDOCT from 15,173 eyes of 8878 patients with glaucoma or suspected of having the disease extracted from the Duke Glaucoma Registry. The data set was randomly divided at the patient level in training and test sets. A convolutional neural network (CNN) was initially trained and validated to predict the 52 sensitivity threshold points of the 24-2 SAP from the 768 RNFL thickness points of the SDOCT peripapillary scan. Simulated localized RNFL defects of varied locations and depths were created by modifying the normal average peripapillary RNFL profile. The simulated profiles were then fed to the previously trained CNN, and the topographic SF relationships between structural defects and SAP functional losses were investigated. Results: The CNN predictions had an average correlation coefficient of 0.60 (P < 0.001) with the measured values from SAP and a mean absolute error of 4.25 dB. Simulated RNFL defects led to well-defined arcuate or paracentral visual field losses in the opposite hemifield, which varied according to the location and depth of the simulations. Conclusions: A CNN was capable of predicting SAP sensitivity thresholds from SDOCT RNFL thickness measurements and generate an SF map from simulated defects. Translational Relevance: AI-based SF map improves the understanding of how SDOCT losses translate into detectable SAP damage.