Race, Ethnicity, Insurance, and Population Density Associations with Pediatric Strabismus and Strabismic Amblyopia in the IRIS® Registry.

PURPOSE: To evaluate the associations of sociodemographic factors with pediatric strabismus diagnosis and outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) patients with strabismus diagnosed before the age of 10 years. METHODS: Multivariable regression models evaluated the associations of race and ethnicity, insurance, population density, and ophthalmologist ratio with age at strabismus diagnosis, diagnosis of amblyopia, residual amblyopia, and strabismus surgery. Survival analysis evaluated the same predictors of interest with the outcome of time to strabismus surgery. MAIN OUTCOME MEASURES: Age at strabismus diagnosis, rate of amblyopia and residual amblyopia, and rate of and time to strabismus surgery. RESULTS: The median age at diagnosis was 5 years (interquartile range, 3-7) for 106 723 children with esotropia (ET) and 54 454 children with exotropia (XT). Amblyopia diagnosis was more likely with Medicaid insurance than commercial insurance (odds ratio [OR], 1.05 for ET; 1.25 for XT; P < 0.01), as was residual amblyopia (OR, 1.70 for ET; 1.53 for XT; P < 0.01). For XT, Black children were more likely to develop residual amblyopia than White children (OR, 1.34; P < 0.01). Children with Medicaid were more likely to undergo surgery and did so sooner after diagnosis (hazard ratio [HR], 1.23 for ET; 1.21 for XT; P < 0.01) than those with commercial insurance. Compared with White children, Black, Hispanic, and Asian children were less likely to undergo ET surgery and received surgery later (all HRs < 0.87; P < 0.01), and Hispanic and Asian children were less likely to undergo XT surgery and received surgery later (all HRs < 0.85; P < 0.01). Increasing population density and clinician ratio were associated with lower HR for ET surgery (P < 0.01). CONCLUSIONS: Children with strabismus covered by Medicaid insurance had increased odds of amblyopia and underwent strabismus surgery sooner after diagnosis compared with children covered by commercial insurance. After adjusting for insurance status, Black, Hispanic, and Asian children were less likely to receive strabismus surgery with a longer delay between diagnosis and surgery compared with White children. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Predictors of Long-term Ophthalmic Complications after Closed Globe Injuries Using the Intelligent Research in Sight (IRIS®) Registry.

Purpose: To identify clinical factors associated with the need for future surgical intervention following closed globe ocular trauma. Design: Retrospective cohort study. Subjects Participants and/or Controls: Patients in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry with a diagnosis of closed globe ocular trauma occurring between 2013 and 2019, identified using International Classification of Disease, 10th Revision and Systematized Nomenclature of Medicine codes. Methods: Diagnosis codes were used to identify multiple concomitant diagnoses present on the date of closed globe ocular trauma. Survival analyses were performed for each outcome of interest, and linear regression was used to identify clinical factors associated with the risk of surgical intervention. Main Outcome Measures: Outcomes included retinal break treatment, retinal detachment (RD) repair, retinal break treatment or RD repair, glaucoma surgery, and cataract surgery. Results: Of the 206 807 patients with closed globe ocular trauma, 9648 underwent surgical intervention during the follow-up period (mean, 444 days): 1697 (0.8%) had RD repair, 1658 (0.8%) had retinal break treatment, 600 (0.3%) had glaucoma surgery, and 5693 (2.8%) had cataract surgery. Traumatic cataract was the strongest risk factor for cataract surgery (hazard ratio, 13.0; 95% confidence interval, 10.8-15.6), traumatic hyphema showed highest risk for glaucoma surgery (7.24; 4.60-11.4), and vitreous hemorrhage was the strongest risk factor for retinal break treatment and detachment repair (11.01; 9.18-13.2 and 14.2; 11.5-17.6, respectively) during the first 60 days after trauma date. Vitreous hemorrhage was a risk factor for cataract surgery at > 60 days after trauma date only. Iris-angle injury was the strongest risk factor for glaucoma surgery > 60 days after trauma, while vitreous hemorrhage remained the strongest factor for retinal break treatment and detachment repair at > 60 days. Traumatic hyphema was a risk factor for all surgical outcomes during all follow-up intervals. Conclusions: Diagnosis of concomitant traumatic cataract, vitreous hemorrhage, traumatic hyphema, and other risk factors may increase the likelihood of requiring surgical intervention after closed globe ocular trauma.

Demographics and Seasonality of Retinal Detachment, Retinal Breaks, and Posterior Vitreous Detachment from the Intelligent Research in Sight Registry.

Purpose: To investigate the incidence, seasonal variation, and differences among age, sex, and race for rhegmatogenous retinal detachment (RRD) repair, retinal break (RB) treatment, and posterior vitreous detachment (PVD) in the Intelligent Research in Sight (IRIS) Registry. Design: Retrospective database study. Participants: Patients in the IRIS Registry who underwent RRD repair, RB treatment, or cataract surgery (CS) based on Current Procedural Terminology codes and PVD diagnosis based on International Classification of Diseases, Ninth and Tenth Revision, codes. Methods: Daily incidence rates were defined as the ratio of patients who underwent RRD repair or RB treatment and patients with a diagnosis of PVD to the total number of patients followed on a given day within the IRIS Registry. The CS group was included as a comparison for seasonal variation. Rates were stratified by decade of life, sex, and race. Main Outcome Measures: Time series trends for incidence rates of RRD, RB, and PVD. Results: A total of 7 115 774 patients received a diagnosis of incident PVD, 237 646 patients underwent RRD repair, and 359 022 patients underwent RB treatment. Also included were 5 940 448 patients who underwent CS. The mean daily incidence for RRD repair, RB treatment, PVD diagnosis, and CS were 0.46 per 100 000 patients, 0.70 per 100 000 patients, 13.90 per 100 000 patients, and 11.80 per 100 000 patients, respectively. Men showed higher incidence of RRD repair and RB treatment than women, whereas women showed higher incidence of PVD diagnosis. Rhegmatogenous retinal detachment incidence was higher in White people compared with other races. Seasonal decreases in PVD, RB treatment, RRD repair, and CS corresponded to national holidays, with larger decreases in winter months. Kaplan-Meier estimates showed that RRD repair and RB treatment typically occurred within 60 days of PVD diagnosis. Conclusions: Within the IRIS Registry, the highest incidence of RRD was in the 6th and 7th decade of life. There was a higher incidence of RRD repair and RB treatment in men compared with women. The seasonal variation associated with national holidays was less pronounced for RRD repair and RB treatment.

Endophthalmitis Rate in Immediately Sequential versus Delayed Sequential Bilateral Cataract Surgery within the Intelligent Research in Sight (IRIS®) Registry Data.

PURPOSE: To compare the rate of postoperative endophthalmitis after immediately sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry database. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the IRIS Registry who underwent cataract surgery from 2013 through 2018. METHODS: Patients who underwent cataract surgery were divided into 2 groups: (1) ISBCS and (2) DSBCS (second-eye surgery ≥1 day after the first-eye surgery) or unilateral surgery. Postoperative endophthalmitis was defined as endophthalmitis occurring within 4 weeks of surgery by International Classification of Diseases (ICD) code and ICD code with additional clinical criteria. MAIN OUTCOME MEASURES: Rate of postoperative endophthalmitis. RESULTS: Of 5 573 639 IRIS Registry patients who underwent cataract extraction, 165 609 underwent ISBCS, and 5 408 030 underwent DSBCS or unilateral surgery (3 695 440 DSBCS, 1 712 590 unilateral surgery only). A total of 3102 participants (0.056%) met study criteria of postoperative endophthalmitis with supporting clinical findings. The rates of endophthalmitis in either surgery eye between the 2 surgery groups were similar (0.059% in the ISBCS group vs. 0.056% in the DSBCS or unilateral group; P = 0.53). Although the incidence of endophthalmitis was slightly higher in the ISBCS group compared with the DSBCS or unilateral group, the odds ratio did not reach statistical significance (1.08; 95% confidence interval, 0.87-1.31; P = 0.47) after adjusting for age, sex, race, insurance status, and comorbid eye disease. Seven cases of bilateral endophthalmitis with supporting clinical data in the DSBCS group and no cases in the ISBCS group were identified. CONCLUSIONS: Risk of postoperative endophthalmitis was not statistically significantly different between patients who underwent ISBCS and DSBCS or unilateral cataract surgery.

Refractive Outcomes After Immediate Sequential vs Delayed Sequential Bilateral Cataract Surgery.

Importance: Approximately 2 million cataract operations are performed annually in the US, and patterns of cataract surgery delivery are changing to meet the increasing demand. Therefore, a comparative analysis of visual acuity outcomes after immediate sequential bilateral cataract surgery (ISBCS) vs delayed sequential bilateral cataract surgery (DSBCS) is important for informing future best practices. Objective: To compare refractive outcomes of patients who underwent ISBCS, short-interval (1-14 days between operations) DSBCS (DSBCS-14), and long-interval (15-90 days) DSBCS (DSBCS-90) procedures. Design, Setting, and Participants: This retrospective cohort study used population-based data from the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry. A total of 1 824 196 IRIS Registry participants with bilateral visual acuity measurements who underwent bilateral cataract surgery were assessed. Exposures: Participants were divided into 3 groups (DSBCS-90, DSBCS-14, and ISBCS groups) based on the timing of the second eye surgery. Univariable and multivariable linear regression models were used to analyze the refractive outcomes of the first and second surgery eye. Main Outcomes and Measures: Mean postoperative uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) after cataract surgery. Results: This study analyzed data from 1 824 196 patients undergoing bilateral cataract surgery (mean [SD] age for those <87 years, 70.03 [7.77]; 684 916 [37.5%] male). Compared with the DSBCS-90 group, after age, self-reported race, insurance status, history of age-related macular degeneration, diabetic retinopathy, and glaucoma were controlled for, the UCVA of the first surgical eye was higher by 0.41 (95% CI, 0.36-0.45; P < .001) letters, and the BCVA was higher by 0.89 (95% CI, 0.86-0.92; P < .001) letters in the DSBCS-14 group, whereas in the ISBCS group, the UCVA was lower by 2.79 (95% CI, -2.95 to -2.63; P < .001) letters and the BCVA by 1.64 (95% CI, -1.74 to -1.53; P < .001) letters. Similarly, compared with the DSBCS-90 group for the second eye, in the DSBCS-14 group, the UCVA was higher by 0.79 (95% CI, 0.74-0.83; P < .001) letters and the BCVA by 0.48 (95% CI, 0.45-0.51; P < .001) letters, whereas in the ISBCS group, the UCVA was lower by -1.67 (95% CI, -1.83 to -1.51; P < .001) letters and the BCVA by -1.88 (95% CI, -1.98 to -1.78; P < .001) letters. Conclusions and Relevance: The results of this cohort study of patients in the IRIS Registry suggest that compared with DSBCS-14 or DSBCS-90, ISBCS is associated with worse visual outcomes, which may or may not be clinically relevant, depending on patients' additional risk factors. Nonrandom surgery group assignment, confounding factors, and large sample size could account for the small but statistically significant differences noted. Further studies are warranted to determine whether these factors should be considered clinically relevant when counseling patients before cataract surgery.

Cataract Surgery Is Not Associated with Decreased Risk of Retinal Vein Occlusion.

Purpose: To evaluate whether cataract surgery is associated with decreased risks of central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) development using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. Design: Retrospective database study of the IRIS Registry data. Participants: Patients in the IRIS Registry who underwent cataract surgery and 1:1 matched control participants from the IRIS Registry using a decision tree classifier as a propensity model. Methods: Control and treatment groups initially were selected using Current Procedural Terminology codes for uncomplicated cataract surgery and other straightforward criteria. To accomplish treatment-control matching, a decision tree classifier was trained to classify patients as treatment versus control based on a set of chosen predictors for treatment, where best-corrected visual acuity and age were the most important predictors. Treatment and control participants subsequently were matched using the classifier, the visit dates, and the identifications of the practice. Cox regression was performed on the matched groups to measure the hazard ratio (HR) of retinal vein occlusion development adjusted for age, sex, race, primary insurance type, and previous diagnosis of diabetic retinopathy (DR), glaucoma, and narrow angles. Main Outcome Measure: The HR of retinal vein occlusion developing in patients who underwent cataract surgery compared with matched control participants. Results: The HRs for CRVO and BRVO developing in patients who underwent cataract surgery compared with matched control participants who did not during the first year after either cataract surgery or baseline visit were 1.26 [95% confidence interval [CI], 1.16-1.38; P < 0.001] and 1.27 [95% CI, 1.19-1.36; P < 0.001], respectively, after controlling for age, sex, race, insurance, and history of DR, glaucoma, and narrow angles. Diabetic retinopathy was the strongest predictor associated with CRVO (2.79 [95% CI, 2.43-3.20; P < 0.001]) and BRVO (2.35 [95% CI, 2.09-2.64; P < 0.001]) development after cataract surgery. Conclusions: Cataract surgery is associated with a small increase in risk of retinal vein occlusions within the first year; however, the incidence is low and likely not clinically significant.

Immunohistochemical application of a highly sensitive and specific murine monoclonal antibody recognising the extracellular domain of the human hepatocyte growth factor receptor (MET).

AIMS: Development of novel targeted therapies directed against hepatocyte growth factor (HGF) or its receptor (MET) necessitates the availability of quality diagnostics to facilitate their safe and effective use. Limitations of some commercially available anti-MET antibodies have prompted development of the highly sensitive and specific clone A2H2-3. Here we report its analytical properties when applied by an automated immunohistochemistry method. METHODS AND RESULTS: Excellent antibody specificity was demonstrated by immunoblot, ELISA, and IHC evaluation of characterised cell lines including NIH3T3 overexpressing the related kinase MST1R (RON). Sensitivity was confirmed by measurements of MET in cell lines or characterised tissues. IHC correlated well with FISH and quantitative RT-PCR assessments of MET (P < 0.001). Good total agreement (89%) was observed with the anti-MET antibody clone SP44 using whole-tissue sections, but poor positive agreement (21-47%) was seen in tissue microarray cores. Multiple lots displayed appropriate reproducibility (R(2)  > 0.9). Prevalence of MET positivity by IHC was higher in non-squamous cell NSCLC, MET or EGFR amplified cases, and in tumours harbouring abnormalities in EGFR exon 19 or 21. CONCLUSIONS: The anti-MET antibody clone A2H2-3 displays excellent specificity and sensitivity. These properties make it suitable for clinical trial investigations and development as a potential companion diagnostic.