The Association of Race, Ethnicity, and Insurance Status with the Visual Acuity of Retinoblastoma Survivors in the IRIS® Registry.

PURPOSE: To identify sociodemographic factors associated with the visual outcomes of retinoblastoma survivors. METHODS: Retrospective cohort study using a US-based clinical data registry. All individuals < 18 years of age with a history of retinoblastoma in the Intelligent Research in Sight (IRIS®) Registry (1/1/2013-12/31/2020). The primary outcome was visual acuity below the threshold for legal blindness (20/200 or worse) in at least one eye. Multivariable logistic regression was used to evaluate the association between visual outcomes and age, sex, laterality, race, ethnicity, type of insurance, and geographic location. RESULTS: This analysis included 1545 children with a history of retinoblastoma. The median length of follow-up was 4.1 years (IQR, 2.2-5.9 years) and the median age at most recent clinical visit was 12 years (IQR, 8-16 years). Retinoblastoma was unilateral in 54% of cases. Poor vision in at least one eye was identified in 78% of all children and poor vision in both eyes in 17% of those with bilateral disease. Poor visual outcomes were associated with unilateral diagnosis (OR, 1.55; 95% CI,1.13-2.12; p = .007), Black race (OR, 2.03; 95% CI, 1.19-3.47; p = .010), Hispanic ethnicity (OR, 1.65; 95% CI, 1.16-2.37; p = .006), and non-private insurance (OR, 1.47; 95% CI, 1.02-2.10; p = .037). CONCLUSIONS: Poor visual outcomes appear to be more common among Black, Hispanic, and publicly insured children with a history of retinoblastoma, raising concerns regarding healthcare inequities. Primary care physicians should ensure that young children receive red reflex testing during routine visits and consider retinoblastoma in the differential diagnosis of abnormal eye exams.

Racial Disparities in Glaucoma Vision Outcomes and Eye Care Utilization: An IRIS Registry Analysis.

PURPOSE: To evaluate racial disparities in vision outcomes and eye care utilization among glaucoma patients. DESIGN: Retrospective cohort study. METHODS: In this population-based IRIS Registry (Intelligent Research in Sight) study, we included patients with minimum one diagnosis code for glaucoma at least 6 months prior to January 1, 2015 and at least one eye exam, visual field (VF), optical coherence tomography (OCT), or eye-related inpatient or emergency department (ED) code in 2015. Multivariable logistic and negative binomial regression models were used to assess vision and utilization outcomes, respectively, across race and ethnicity from January 1, 2015 to January 1, 2020. Vision outcomes included cup-to-disc ratio (CDR) progression > 0.80, poor vision (visual acuity 20/200 or worse), low vision codes, and need for glaucoma filtering surgery. Utilization outcomes included outpatient eye exams, OCTs, VFs, inpatient/ED encounters, and lasers/surgeries. RESULTS: Among 996,297 patients, 73% were non-Hispanic White, 15% non-Hispanic Black, 9% Hispanic, 3% Asian/Pacific Islander, and 0.3% Native American/Alaska Native. Compared to White eyes, Black and Hispanic eyes had higher adjusted odds of CDR progression (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.08-1.17; OR = 1.28, 95% CI = 1.22-1.34), poor vision (OR = 1.26, 95% CI = 1.22-1.29; OR = 1.26, 95% CI = 1.22-1.31), glaucoma filtering surgery (rate ratio (RR) = 1.47, 95% CI = 1.42-1.51; RR = 1.13, 95% CI = 1.09-1.18). Hispanic eyes also had increased odds of low vision diagnoses (Hispanic OR = 1.18, 95% CI = 1.07-1.30). Black and Hispanic patients were less likely to have eye exams (RR = 0.94, 95% CI = 0.94-0.95; RR = 0.99, 95% CI = 0.99-0.99) and OCTs (RR = 0.86, 95% CI = 0.85-0.86; RR = 0.97, 95% CI = 0.96-0.98), yet Black patients had higher odds of inpatient/ED encounters (RR = 1.64, 95% CI = 1.37-1.96) compared to White patients. Native American patients were more likely to have poor vision (OR = 1.17, 95% CI = 1.01-1.36) and less likely to have outpatient visits (RR = 0.89, 95% CI = 0.86-0.91), OCTs (RR = 0.85, 95% CI = 0.82-0.89), visual fields (RR = 0.91, 95% CI = 0.88-0.94) or lasers/surgeries (RR = 0.87, 95% CI = 0.79-0.96) compared to White patients. CONCLUSIONS: We found that significant disparities in US eye care exist with Black, Hispanic, and Native American patients having worse vision outcomes and less disease monitoring. Glaucoma may be undertreated in these racial and ethnic minority groups, increasing risk for glaucoma-related vision loss.

Effectiveness of Angle-Based Minimally Invasive Glaucoma Surgery after Laser Trabeculoplasty: An Analysis of the IRIS® Registry (Intelligent Research in Sight).

OBJECTIVE: Angle-based minimally invasive glaucoma surgery (ab-MIGS) has grown substantially, although long-term efficacy is poorly understood. We analyze ab-MIGS effectiveness with and without preceding laser trabeculoplasty (LTP). DESIGN: Retrospective cohort study. SUBJECTS: Eyes undergoing ab-MIGS (Canaloplasty, Goniotomy, Trabectome, and iStent) with and without prior laser trabeculoplasty (< 2 years preceding MIGS) were identified in the IRIS® Registry (Intelligent Research in Sight) 2013 to 2018. METHODS: Propensity score matching (PSM) was undertaken to define the following 4 cohorts: (1) standalone ab-MIGS, no prior LTP vs. (2) standalone ab-MIGS, with prior LTP; and (3) ab-MIGS + phacoemulsification, no prior LTP vs. (4) ab-MIGS + phacoemulsification, with prior LTP. MAIN OUTCOME MEASURES: Failure was defined as subsequent glaucoma reoperation after ab-MIGS (either MIGS or traditional glaucoma surgery). Time-to-event outcome and incidence rates were calculated using survival analysis, and adjusted hazard ratios (aHRs) were generated using multivariate Cox proportional hazards models. Medication data were not available for analysis. RESULTS: A total of 164 965 unique MIGS procedures were performed, from 2013 to 2018. After PSM, we identified 954 eyes undergoing standalone ab-MIGS and 7522 undergoing ab-MIGS + phacoemulsification. For eyes undergoing standalone ab-MIGS, those with prior LTP (n = 477) were more likely to undergo reoperation vs. those without LTP (n = 477) at 6 and 12 months. In multivariable models, those with prior LTP were more likely to undergo reoperation over the 36-month period vs. those without prior LTP (aHR, 1.53; CI, 1.15-2.04; P = 0.004). For eyes undergoing ab-MIGS + phacoemulsification, those with prior LTP (n = 3761) were more likely to undergo reoperation vs. those without LTP (n = 3761) at 12, 24, and 36 months. In multivariable models, those with prior LTP were more likely to undergo reoperation over the 36-month period vs. those without prior LTP (aHR, 1.53 CI, 1.15-2.04; P = 0.004). CONCLUSIONS: Prior LTP may be associated with a higher chance of subsequent glaucoma surgery following ab-MIGS, either with or without concurrent phacoemulsification. These findings have important implications for understanding who may benefit most from ab-MIGS, and for guiding patient and surgeon treatment expectations. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Incidence of Strabismus After Upper and Lower Blepharoplasty in the United States.

PURPOSE: To compare the incidence of strabismus after upper and lower blepharoplasty in the United States. METHODS: Retrospective cohort study of adults (age ≥18 years) in the IRIS Registry (Intelligent Research in Sight) who underwent blepharoplasty between January 1, 2013 and December 31, 2020. The primary outcome was the Kaplan-Meier estimated cumulative incidence of strabismus diagnosis and surgery within 3 years of blepharoplasty. Multivariable Cox regression was used to determine the association of blepharoplasty type with strabismus diagnosis and surgery, adjusting for patient age, sex, and geographic region. RESULTS: Blepharoplasty was performed in 368,623 patients (median [interquartile range] age, 69 [63-75] years, and 69% female). Compared with those undergoing upper eyelid blepharoplasty, patients treated with lower eyelid blepharoplasty were slightly younger (median age, 66 vs. 69 years; p < 0.001) and more likely to be female (71% vs. 69%; p < 0.001). There was a greater 3-year incidence of strabismus diagnosis (2.0% vs. 1.5%; p < 0.001) and a greater 3-year incidence of strabismus surgery (0.15% vs. 0.06%; p = 0.003) for individuals undergoing lower vs. upper blepharoplasty. After adjusting for age, sex, and geographic region, lower blepharoplasty was associated with a higher 3-year risk of strabismus diagnosis (HR, 1.49; 95% CI, 1.23-1.81; p < 0.001) and surgery (HR, 2.53; 95% CI, 1.27-5.03; p = 0.008). CONCLUSIONS: This registry-based analysis found that individuals undergoing lower eyelid blepharoplasty were at higher risk of strabismus compared with those undergoing upper eyelid blepharoplasty. Using large databases to understand the incidence of complications of frequently performed procedures may improve ophthalmologists' ability to provide data-driven counseling on surgical risks prior to intervention.

Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS® Registry Analysis.

BACKGROUND AND OBJECTIVE: This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS® Registry. PATIENTS AND METHODS: This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed. RESULTS: The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion. CONCLUSIONS: In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:220-226.].

Risk Factors for Glaucoma Diagnosis and Surgical Intervention following Pediatric Cataract Surgery in the IRIS® Registry.

PURPOSE: To compare demographic and clinical factors associated with glaucoma following cataract surgery (GFCS) and glaucoma surgery rates between infants, toddlers, and older children using a large, ophthalmic registry. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the IRIS® Registry (Intelligent Research in Sight) who underwent cataract surgery at ≤ 17 years old and between January 1, 2013 and December 31, 2020. METHODS: Glaucoma diagnosis and procedural codes were extracted from the electronic health records of practices participating in the IRIS Registry. Children with glaucoma diagnosis or surgery before cataract removal were excluded. The Kaplan-Meier estimator was used to determine the cumulative probability of GFCS diagnosis and glaucoma surgery after cataract surgery. Multivariable Cox regression was used to identify factors associated with GFCS and glaucoma surgery. MAIN OUTCOME MEASURES: Cumulative probability of glaucoma diagnosis and surgical intervention within 5 years after cataract surgery. RESULTS: The study included 6658 children (median age, 10.0 years; 46.2% female). The 5-year cumulative probability of GFCS was 7.1% (95% confidence interval [CI], 6.1%-8.1%) and glaucoma surgery was 2.6% (95% CI, 1.9%-3.2%). The 5-year cumulative probability of GFCS for children aged < 1 year was 22.3% (95% CI, 15.7%-28.4%). Risk factors for GFCS included aphakia (hazard ratio [HR], 2.63; 95% CI, 1.96-3.57), unilateral cataract (HR, 1.48; 95% CI, 1.12-1.96), and Black race (HR, 1.61; 95% CI, 1.12-2.32). The most common surgery was glaucoma drainage device insertion (32.6%), followed by angle surgery (23.3%), cyclophotocoagulation (15.1%), and trabeculectomy (5.8%). CONCLUSIONS: Glaucoma following cataract surgery diagnosis in children in the IRIS Registry was associated with young age, aphakia, unilateral cataract, and Black race. Glaucoma drainage device surgery was the preferred surgical treatment, consistent with the World Glaucoma Association 2013 consensus recommendations for GFCS management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Surgical Approach and Reoperation Risk in Intermittent Exotropia in the IRIS Registry.

Importance: There is no consensus on the optimal surgical treatment for children with intermittent exotropia (IXT). Objective: To compare the 5-year reoperation rates for children with IXT treated with horizontal muscle strabismus surgery using bilateral lateral rectus recession (BLR) vs unilateral lateral rectus recession with medial rectus resection (RR). Design, Setting, and Participants: This cohort study examined data obtained from the Intelligent Research in Sight (IRIS) Registry on 7482 children (age, <18 years) with IXT who underwent horizontal eye muscle strabismus surgery between January 1, 2013, and December 31, 2017. Children undergoing initial surgeries involving 3 or more horizontal muscles, vertical muscles, or reoperations were excluded. Main Outcomes and Measures: The primary outcome was the adjusted cumulative incidence of repeat horizontal muscle surgery within 5 years after the initial surgery. Reoperation risk was analyzed using adjusted hazard ratios (AHRs) derived from multivariable Cox regression models, adjusting for individual demographic and surgical factors (age, sex, race and ethnicity, US Census region, and surgeon subspecialty). Data were analyzed between January 16 and September 20, 2023. Results: The study included 7482 children (median [IQR] age at initial surgery, 6 [4-9] years; 3945 females [53%]) with IXT treated with horizontal muscle strabismus surgery. Bilateral lateral rectus recession was performed more frequently than RR (85.3% vs 14.7%, P < .001), especially in younger children (rates of BLR vs RR by age: age 0 to ≤4 years, 88.4% vs 11.6%; age 5 to ≤11 years, 84.7% vs 15.3%; age 12 to ≤17 years, 78.1% vs 21.9%; P < 0.001). After data adjustment, the 5-year cumulative incidence of reoperation was 21.3% (95% CI, 20.1%-22.5%). The adjusted 5-year cumulative incidence of reoperation was higher for BLR than for RR (22.2% vs 17.2%; difference, 4.9%; 95% CI, 1.9%-8.0%). Unilateral lateral rectus recession with medial rectus resection was associated with a lower 5-year reoperation risk compared with BLR (AHR, 0.77; 95% CI, 0.64-0.93). Younger age at time of initial surgery was associated with a higher reoperation risk (AHR per 1-year decrease, 1.09; 95% CI, 1.07-1.11) after adjusting for all other covariates. Conclusions and Relevance: In this nationwide registry, approximately 1 in 5 children with IXT underwent reoperation within 5 years after the initial surgery. Children treated with RR were less likely to require a reoperation within 5 years compared with those treated with BLR. Further efforts to identify modifiable risk factors for reoperation are needed to reduce the surgical burden and improve outcomes for children with IXT.

Smoking Is Associated With a Higher Risk of Surgical Intervention for Thyroid Eye Disease in the IRIS Registry.

PURPOSE: To describe the association of smoking status with surgical intervention for thyroid eye disease (TED) at the population-level. DESIGN: Retrospective cohort study. METHODS: This study included all adults (aged ≥18 years) with Graves disease in the Intelligent Research in Sight (IRIS) Registry (January 1, 2013, to December 31, 2020). The primary outcome was surgical intervention for TED, stratified into orbital decompression, strabismus surgery, and eyelid recession surgery. The Kaplan-Meier estimated 5-year cumulative probability for each surgical intervention was calculated. Multivariable Cox regression was used to evaluate the association between smoking status and each surgical intervention, adjusting for age, sex, race, ethnicity, and geographic region. RESULTS: This study included 87,774 patients. Median age was 59 years (IQR, 48-68 years); 81% were female patients. Current smokers had a greater 5-year cumulative probability of orbital decompression (3.7% vs 1.9%; P < .001), strabismus surgery (4.6% vs 2.2%; P < .001), and eyelid recession (4.1% vs 2.6%; P < .001) compared to never smokers. After adjusting for demographic factors, current smokers were at greater risk for orbital decompression (hazard ratio [HR], 2.1; 95% CI, 1.8-2.4; P < .001), strabismus surgery (HR, 2.0; 95% CI, 1.8-2.3; P < .001), and eyelid recession (HR, 1.7; 95% CI, 1.5-1.9; P < .001) than never smokers. Former smokers were at higher risk for each type of surgery for TED, albeit at lower levels than current smokers. CONCLUSIONS: Smoking was associated with increased risk of surgical intervention for TED in the IRIS Registry. Former smokers were at a lower risk than current smokers, supporting the role of smoking cessation on lowering the burden of surgical disease at the population-level.

Effectiveness of Microinvasive Glaucoma Surgery in the United States: Intelligent Research in Sight Registry Analysis 2013-2019.

PURPOSE: To evaluate the effectiveness of microinvasive glaucoma surgery (MIGS) with and without concurrent phacoemulsification. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight (IRIS®) Registry who underwent Xen gel stent (ab interno) implantation, endoscopic cyclophotocoagulation (ECP), or goniotomy or canaloplasty from 2013 through 2019. METHODS: Kaplan-Meier survival analysis was used to assess reoperation rates. We defined reoperation as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine factors predictive of reoperation. MAIN OUTCOME MEASURES: Reoperation rate, mean intraocular pressure (IOP) and visual acuity (VA), postoperative complications, predictors of reoperation, and reoperation procedure type. RESULTS: A total of 79 363 eyes from 57 561 patients were included, with 15 118 eyes (19%) receiving stand-alone MIGS and 64 245 eyes (81%) receiving MIGS concurrent with phacoemulsification. Overall, patients who underwent MIGS concurrently with phacoemulsification showed lower reoperation rates compared with stand-alone MIGS, most pronounced in ECP and goniotomy or canaloplasty. At postoperative year 2, the cumulative reoperation rate for stand-alone procedures was 15% for ECP, 24% for Xen implantation, and 24% for goniotomy or canaloplasty compared with 3% for ECP, 19% for Xen implantation, and 6% for goniotomy or canaloplasty concurrent with phacoemulsification (P < 0.001 for each stand-alone MIGS vs. MIGS with phacoemulsification). Black race, older age, moderate and severe glaucoma, higher baseline IOP, and glaucoma subtype were associated with higher reoperation risk. Although IOP decreased in all groups, stand-alone MIGS showed a more substantial decrease in mean IOP. Complication rates from MIGS were low overall: 1% for ECP, 1% for Xen implantation, and 2% for goniotomy or canaloplasty. CONCLUSIONS: In current United States clinical practice, MIGS has substantially lower reoperation rates when performed with phacoemulsification, especially for ECP and goniotomy or canaloplasty. Approximately one-sixth of patients undergoing stand-alone ECP and one-quarter of patients undergoing stand-alone Xen implantation or goniotomy or canaloplasty require reoperation by 2 years. Black race, diagnosis coding of moderate to severe glaucoma, and higher baseline IOP were associated with higher risk of reoperation after MIGS procedures. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Effectiveness of Trabeculectomy and Tube Shunt with versus without Concurrent Phacoemulsification: Intelligent Research in Sight Registry Longitudinal Analysis.

OBJECTIVE: To determine the effectiveness of trabeculectomy and glaucoma drainage device (GDD) surgery performed with concurrent phacoemulsification compared with stand-alone procedures. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight Registry who underwent trabeculectomy or GDD from 2013 through 2019. METHODS: The Kaplan-Meier survival analysis was used to determine reoperation rates. Reoperation was defined as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine reoperation risk factors. MAIN OUTCOME MEASURES: Reoperation rate, intraocular pressure (IOP), visual acuity, reoperation procedure type, postoperative complications, and predictors of surgical failure. RESULTS: A total of 117 697 eyes undergoing glaucoma surgery alone and 35 657 eyes undergoing surgery with phacoemulsification were included. The cumulative reoperation rates at postoperative years 1 and 3 were 4.9% and 11.5%, respectively, for trabeculectomy alone and 3.0% and 7.3%, respectively, for trabeculectomy combined with phacoemulsification (P < 0.001). The reoperation rates at postoperative 1 and 3 years were 3.8% and 7.8%, respectively, for GDD alone and 2.1% and 5.4%, respectively, for GDD with phacoemulsification (P < 0.001). Stand-alone procedures achieved greater IOP reduction by percentage change from baseline (trabeculectomy alone, 35.3% vs. trabeculectomy with phacoemulsification, 23.1%, P < 0.001; and GDD alone, 36.0% vs. GDD with phacoemulsification, 29.3%; P < 0.001). Visual acuity improved by 0.12 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.11-0.12) and 0.10 logMAR (95% CI, 0.08-0.11) after trabeculectomy and GDD with phacoemulsification and declined by 0.15 logMAR (95% CI, 0.14-0.15) and 0.12 logMAR (95% CI, 0.11-0.12) after stand-alone trabeculectomy and GDD. The overall documented complication rate was 2.9% for GDD and 1.4% for trabeculectomy. Age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical failure risk. The most common reoperation procedure was GDD. CONCLUSIONS: Reoperation rates within the first 3 years after trabeculectomy and GDD with and without phacoemulsification were low. Trabeculectomy and GDD with phacoemulsification had lower reoperation rates than those with stand-alone procedures. However, stand-alone procedures resulted in greater IOP reduction compared with combined procedures. Postoperative complications were uncommon overall. Patient age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical success.

Background polygenic risk modulates the association between glaucoma and cardiopulmonary diseases and measures: an analysis from the UK Biobank.

AIMS: To assess whether associations of cardiopulmonary conditions and markers with glaucoma differ by background genetic risk for primary open angle glaucoma (POAG). METHODS: We constructed a POAG polygenic risk score (PRS) using genome-wide association study summary statistics from a large cross-ancestry meta-analysis. History of glaucoma (including self-report and codes for POAG, 'other glaucoma' or unspecified glaucoma), history of common cardiopulmonary conditions and cardiopulmonary measures were assessed in the UK Biobank. Stratifying by PRS decile 1 (lowest risk) versus decile 10 (highest risk), separate multivariable models were estimated to assess the associations of cardiopulmonary diseases or factors with glaucoma, adjusting for age, sex, smoking and medication use. A Bonferroni correction was used to adjust p values for multiple comparisons. RESULTS: Individuals in POAG PRS decile 1 (417 cases, 44 458 controls; mean age 56.8 years) and decile 10 (2135 cases, 42 413 controls; mean age 56.7 years) were included. Within decile 1, glaucoma cases had significantly higher glycated haemoglobin (38.5 vs 35.9 mmol/mol) and higher prevalence of diabetes (17.5% vs 6.5%), dyslipidaemia (31.2% vs 18.3%) and chronic kidney disease (CKD) (6.7% vs 2.0%) than controls (adjusted p<0.0013 for each). Within decile 10, glaucoma was associated with higher prevalence of dyslipidaemia (27.7% vs 17.3%, p=6.9E-05). The magnitude of association between glaucoma and diabetes, CKD and glycated haemoglobin differed between deciles 1 and 10 (contrast test p value for difference <0.05). CONCLUSION: The relations between systemic conditions and glaucoma vary by underlying genetic predisposition to POAG, with larger associations among those who developed glaucoma despite low genetic risk.

Risk Factors Associated With Pterygium Reoperation in the IRIS Registry.

This cohort study used data from the IRIS Registry to assess the risk factors associated with pterygium reoperation.

Adjustable Suture Technique Is Associated with Fewer Strabismus Reoperations in the Intelligent Research in Sight Registry.

PURPOSE: To compare the reoperation rates after strabismus surgery with and without the adjustable suture technique. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or older in the Intelligent Research in Sight (IRIS®) Registry who underwent strabismus surgery between January 1, 2013, and December 31, 2018. METHODS: Data were collected from the electronic health records of practices participating in the IRIS Registry. The primary exposure of interest was use of the adjustable suture technique, identified by Current Procedural Terminology coding. MAIN OUTCOME MEASURES: The primary outcome was repeat strabismus surgery within 1 year of initial strabismus surgery. Odds ratios (ORs) were derived from a multivariable logistic regression model evaluating the association between the use of adjustable sutures and reoperation rate, adjusting for patient demographics and surgical factors. RESULTS: A total of 34 872 patients who underwent strabismus surgery during the study interval were identified: 72% underwent horizontal muscle surgery, 17% underwent vertical muscle surgery, and 11% underwent combined horizontal and vertical muscle surgery. Adjustable sutures were used in 18% of patients. The overall reoperation rate within 1 year of strabismus surgery was 7.7%. The 1-year reoperation rate was 6.0% for patients treated with adjustable sutures and 8.1% for patients treated without adjustable sutures (P < 0.001). The multivariable regression model revealed a statistically significant 30% decrease in the odds of reoperation within 1 year of surgery when adjustable sutures were used (OR, 0.70; 95% confidence interval [CI], 0.62-0.78), a 40% increase in those with a history of prior strabismus surgery (OR, 1.40; 95% CI, 1.28-1.53), and a 9% increase per decade of age at surgery (OR, 1.09; 95% CI, 1.06-1.11). CONCLUSIONS: In adults cared for in practices participating in the IRIS Registry, the adjustable suture technique was associated with a significantly lower reoperation rate within 1 year of undergoing horizontal or combined horizontal and vertical strabismus surgery. Adjustable suture use in vertical strabismus surgery alone did not reduce the 1-year reoperation rate significantly. A history of prior strabismus surgery was associated with increased odds of reoperation.

Unsupervised Machine Learning Shows Change in Visual Field Loss in the Idiopathic Intracranial Hypertension Treatment Trial.

PURPOSE: We previously reported that archetypal analysis (AA), a type of unsupervised machine learning, identified and quantified patterns of visual field (VF) loss in idiopathic intracranial hypertension (IIH), referred to as archetypes (ATs). We assessed whether AT weight changes over time are consistent with changes in conventional global indices, whether visual outcome or treatment effects are associated with select AT, and whether AA reveals residual VF defects in eyes deemed normal after treatment. DESIGN: Analysis of data collected from a randomized controlled trial. PARTICIPANTS: Two thousand eight hundred sixty-two VFs obtained from 165 participants during the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: We applied a 14-AT model derived from IIHTT VFs. We examined changes in individual AT weights over time for all study eyes and evaluated differences between treatment groups. We created an AT change score to assess overall VF change from baseline. We tested threshold baseline AT weights for association with VF outcome and treatment effect at 6 months. We determined the abnormal ATs with meaningful weight at outcome for VFs with a mean deviation (MD) of -2.00 dB or more. MAIN OUTCOME MEASURES: Individual AT weighting coefficients and MD. RESULTS: Archetype 1 (a normal VF pattern) showed the greatest weight change for all study eyes, increasing from 11.9% (interquartile range [IQR], 0.44%-24.1%) at baseline to 31.2% (IQR, 16.0%-45.5%) at outcome (P < 0.001). Archetype 1 weight change (r = 0.795; P < 0.001) and a global score of AT change (r = 0.988; P < 0.001) correlated strongly with MD change. Study eyes with baseline AT2 (a mild diffuse VF loss pattern) weight of 44% or more (≥ 1 standard deviation more than the mean) showed higher AT2 weights at outcome than those with AT2 weight of < 44% at baseline (P < 0.001). Only the latter group showed a significant acetazolamide treatment effect. Archetypal analysis revealed residual VF loss patterns, most frequently representing mild diffuse loss and an enlarged blind spot in 64 of 66 study eyes with MD of -2.00 dB or more at outcome. CONCLUSIONS: Archetypal analysis provides a quantitative approach to monitoring VF changes in IIH. Baseline AT features may be associated with treatment response and VF outcome. Archetypal analysis uncovers residual VF defects not otherwise revealed by MD.

Risk Factors for Glaucoma Drainage Device Revision or Removal Using the IRIS Registry.

PURPOSE: To elucidate risk factors for revision or removal of glaucoma drainage devices (GDD) in glaucoma patients in the United States. DESIGN: Retrospective cohort study. METHODS: IRIS Registry (Intelligent Research in Sight) patients who underwent GDD insertion between January 1, 2013 and December 31, 2018 were included. Various demographic and clinical factors were collected. Kaplan-Meier survival plots, Cox proportional-hazard models utilizing Firth's Penalized Likelihood, and multivariate linear regression models were used. The main outcome measures were hazard ratios (HR) and beta coefficient (ß) estimates. RESULTS: A total of 44,330 distinct patients underwent at least 1 GDD implantation, and 3354 of these underwent subsequent GDD revision or removal surgery. With failure defined as GDD revision/removal, factors significantly associated with decreased failure included unknown race (HR = 0.83; P = .004) and unknown ethnicity (HR = 0.68; P < .001). Factors associated with increased risk of GDD revision/removal surgery included presence of chronic angle-closure glaucoma (HR = 1.32; P < .001) and dry eye disease (HR = 1.30; P = .007). Additionally, factors associated with a decreased average time (in days) to GDD revision/removal included male sex (ß = -25.96; P = .044), unknown race (ß = -55.28; P = .013), and right-eye laterality (ß = -38.67; P = .026). Factors associated with an increased average time to GDD revision/removal included having a history of a past eye procedure (ß = 104.83; P < .001) and being an active smoker (ß = 38.15; P = .024). CONCLUSIONS: The size and scope of the IRIS Registry allows for detection of subtle associations between risk factors and GDD revision or removal surgery. The aforementioned demographic and clinical factors may all have an impact on GDD longevity and can inform the treatment options available for glaucoma patients.

Photoreceptor Layer Thinning Is an Early Biomarker for Age-Related Macular Degeneration: Epidemiologic and Genetic Evidence from UK Biobank OCT Data.

PURPOSE: Despite widespread use of OCT, an early-stage imaging biomarker for age-related macular degeneration (AMD) has not been identified. Pathophysiologically, the timing of drusen accumulation in relationship to photoreceptor degeneration in AMD remains unclear, as are the inherited genetic variants contributing to these processes. Herein, we jointly analyzed OCT, electronic health record data, and genomic data to characterize the time sequence of changes in retinal layer thicknesses in AMD, as well as epidemiologic and genetic associations between retinal layer thicknesses and AMD. DESIGN: Cohort study. PARTICIPANTS: Forty-four thousand eight hundred twenty-three individuals from the UK Biobank (enrollment age range, 40-70 years; 54% women; median follow-up, 10 years). METHODS: The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we associated AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age-squared (age2), sex, smoking status, and principal components of ancestry. MAIN OUTCOME MEASURES: Prevalent and incident AMD. RESULTS: Photoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed, whereas retinal pigment epithelium (RPE) and Bruch's membrane (BM) complex thickening started after 57 years of age. Each standard deviation (SD) of PS thinning and RPE-BM complex thickening was associated with incident AMD (PS: hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.23-1.47; P = 3.7 × 10-11; RPE-BM complex: HR, 1.14; 95% CI, 1.06-1.22; P = 0.00024). The AMD PRS was associated with PS thinning (ß, -0.21 SD per twofold genetically increased risk of AMD; 95% CI, -0.23 to -0.19; P = 2.8 × 10-74), and its association with RPE-BM complex was U-shaped (thinning with AMD PRS less than the 92nd percentile and thickening with AMD PRS more than the 92nd percentile). The loci with strongest support for genetic correlation were AMD risk-raising variants Complement Factor H (CFH):rs570618-T, CFH:rs10922109-C, and Age-Related Maculopathy Susceptibility 2 (ARMS2)/High-Temperature Requirement Serine Protease 1 (HTRA1):rs3750846-C on PS thinning and SYN3/Tissue Inhibitor of Metalloprotease 3 (TIMP3):rs5754227-T on RPE-BM complex thickening. CONCLUSIONS: Epidemiologically, PS thinning precedes RPE-BM complex thickening by decades and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage biomarker for future AMD development.

Usage Patterns of Minimally Invasive Glaucoma Surgery (MIGS) Differ by Glaucoma Type: IRIS Registry Analysis 2013-2018.

PURPOSE: To examine patterns of standard (trabeculectomy or glaucoma drainage devices, GDDs) vs novel (minimally invasive glaucoma surgery, MIGS) surgical techniques in the US. METHODS: We used the American Academy of Ophthalmology (AAO) IRIS® Registry (Intelligent Research in Sight) queried between 2013 and 2018 (inclusive) to calculate the cumulative proportion of stand-alone, concurrent (same day) or sequential (subsequent day) glaucoma surgical techniques performed in each glaucoma diagnosis type. Secondary analyses of adjusted proportions of concurrent and sequential surgeries stratified by glaucoma diagnosis were also performed. RESULTS: Of 203,146 eyes receiving glaucoma surgeries, open angle glaucoma (OAG) was most likely to undergo all types of intervention. The iStent was the most commonly performed MIGS, primarily for those with normal tension glaucoma (NTG) or OAG (p < .001). Conversely, GDD was the most commonly performed procedure in secondary glaucoma or other (specified) glaucoma (p < .001). ECP and iStent were the most common concurrent procedures performed; most often for OAG and NTG (p < .001). After an initial standard surgery, most eyes underwent recurrent standard interventions (90.3%). ECP was the most common MIGS performed after an initial standard surgery; particularly in primary angle-closure (PACG) and secondary glaucoma eyes (p < .001). CONCLUSION: Glaucoma type may influence the choice of glaucoma procedures and the decision to perform concurrent as well sequential surgical procedures. Given the poorly understood long term safety and effectiveness of MIGS, and with substantially increasing use of MIGS procedures in recent years, future studies comparing their safety and effectiveness vs standard interventions, for a variety of glaucoma types, is needed.

Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature.

BACKGROUND: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. METHODS: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases-based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. RESULTS: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). CONCLUSIONS: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.

Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness-the LIFE-Adult Study.

BACKGROUND: Circumpapillary retinal nerve fiber layer thickness (cpRNFLT) as assessed by spectral domain optical coherence tomography (SD-OCT) is a new technique used for the detection and evaluation of glaucoma and other optic neuropathies. Before translating cpRNFLT into clinics, it is crucially important to investigate anthropometric, biochemical, and clinical parameters potentially affecting cpRNFLT in a large population-based dataset. METHODS: The population-based LIFE-Adult Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. All participants underwent standardized systemic assessment of various cardiometabolic risk markers and ocular imaging, including cpRNFLT measurement using SD-OCT (Spectralis, Heidelberg Engineering). After employing strict SD-OCT quality criteria, 8952 individuals were analyzed. Multivariable linear regression analyses were used to evaluate the independent associations of various cardiometabolic risk markers with sector-specific cpRNFLT. For significant markers, the relative strength of the observed associations was compared to each other to identify the most relevant factors influencing cpRNFLT. In all analyses, the false discovery rate method for multiple comparisons was applied. RESULTS: In the entire cohort, female subjects had significantly thicker global and also sectoral cpRNFLT compared to male subjects (p < 0.05). Multivariable linear regression analyses revealed a significant and independent association between global and sectoral cpRNFLT with biomarkers of renal function and lipid profile. Thus, thinner cpRNFLT was associated with worse renal function as assessed by cystatin C and estimated glomerular filtration rate. Furthermore, an adverse lipid profile (i.e., low high-density lipoprotein (HDL) cholesterol, as well as high total, high non-HDL, high low-density lipoprotein cholesterol, and high apolipoprotein B) was independently and statistically significantly related to thicker cpRNFLT. In contrast, we do not observe a significant association between cpRNFLT and markers of inflammation, glucose homeostasis, liver function, blood pressure, or obesity in our sector-specific analysis and globally. CONCLUSIONS: Markers of renal function and lipid metabolism are predictors of sectoral cpRNFLT in a large and deeply phenotyped population-based study independently of previously established covariates. Future studies on cpRNFLT should include these biomarkers and need to investigate whether incorporation will improve the diagnosis of early eye diseases based on cpRNFLT.