Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry.

Purpose: We used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the 2 pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the 2 monthly treatment arms from the clinical trial. Design: Retrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data. Subjects: All treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for 1 year from either the CATT or the IRIS Registry. Methods: Patients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all nonimaging-based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity. Main Outcome Measures: Mean change in visual acuity, in approximated ETDRS letters, between baseline and 1 year for the IRIS Registry prn treatment arms generated by exact matching and IPSW. Results: We identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n = 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n = 261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (exact matching: 1.9 letters ± 14.0 vs. IPSW: 2.8 letters ± 15.0 letters, P = 0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (exact matching: 2.4 letters ± 15.4 vs. IPSW: 2.1 letters ± 16.0 letters, P = 0.79). Conclusions: Both exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared with the clinical trial. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Vitreoretinal Specialist Use of Ancillary Testing: An IRIS® Registry Analysis.

Purpose: To investigate patterns of ancillary imaging testing among vitreoretinal specialists for patients with vitreoretinal disease in the United States (US). Methods: Optical coherence tomography (OCT), color fundus photography (CFP), and fluorescein angiography (FA), ordered by vitreoretinal specialists and documented within the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) between 01 January 2018 and 31 December 2020, were retrospectively assessed. Trends in imaging modality choice were analyzed by payer type, geographic region, and practice type. Sub-analyses were conducted according to categorization of vitreoretinal specialists into those treating a high versus low volume of patients with neovascular age-related macular degeneration (nAMD). Results: OCT was the most common imaging modality used, followed by CFP and FA. Following normalization, the highest volume of OCT procedures performed were identified among Medicare Advantage and Medicare Fee-for-Service beneficiaries, within the South of the US, and at medium and large practices. Minimal differences were observed for CFP and FA volume across payer types and regions. Across practice types, the largest volume of CFP and FA procedures were identified in small and private equity owned practices, respectively. Vitreoretinal specialists with a high nAMD volume more frequently performed OCT than those with a low nAMD volume. Conclusion: Vitreoretinal specialists demonstrated a strong preference for OCT, with real-world associations according to payer type, geographic location, and practice type. Volume of nAMD patients seen impacted the likelihood of specialists ordering OCTs.

Systematic analysis of levels of evidence supporting American Academy of Ophthalmology Preferred Practice Pattern guidelines, 2012-2021.

BACKGROUND: Despite the increased emphasis on evidence-based medicine, the current state of evidence behind ophthalmology clinical practice guidelines is unknown. The purpose of this systematic analysis was to understand the levels of evidence (LOE) supporting American Academy of Ophthalmology (AAO) Preferred Practice Pattern (PPP) guidelines, assess changes over time, and compare LOE across ophthalmology subspecialties. METHODS: All current PPP guidelines and their immediate predecessors were comprehensively reviewed to identify all recommendations with LOE provided (I [randomized controlled trials], II [case-control or cohort studies], and III [nonanalytic studies]). RESULTS: Twenty-three out of 24 current PPPs had a prior edition. Among the PPPs with a prior edition, the number of recommendations with LOE decreased from 1254 in prior PPPs to 94 in current PPPs. The number of recommendations with LOE I decreased from 114 to 83, LOE II decreased from 147 to 2, and LOE III decreased from 993 to 9. However, the proportion of LOE I recommendations increased from 9 to 88%, driven by a disproportionate decrease in reporting of evidence lower than LOE I. Subgroup analysis by subspecialty showed similar trends (LOE I recommendations in prior PPPs vs current PPPs: retina: 57 [12%] vs 19 [100%]; cornea: 33 [5%] vs 24 [100%]; glaucoma: 9 [23%] vs 17 [100%]; cataract: 13 [17%] vs 18 [100%]). CONCLUSIONS: Trends in LOE reporting in PPP guidelines indicate an increasing emphasis on evidence from randomized controlled trials from 2012 to 2021. The decline in the number of recommendations with LOE reported suggests an area for improvement in future guidelines as the presence of LOE is crucial to facilitate interpretation of clinical practice guidelines.

Identifying the mechanism of missingness for unspecified diabetic retinopathy disease severity in the electronic health record: an IRIS® Registry analysis.

Observational studies of diabetic retinopathy (DR) using electronic health record data often determine disease severity using International Classification of Disease (ICD) codes. We investigated the mechanism of missingness for DR severity based on ICD coding using the American Academy of Ophthalmology IRIS® Registry. We included all patient encounters in the registry with a DR ICD-9 or ICD-10 code between January 1, 2014 and June 30, 2021. Demographic, clinical, and practice-level characteristics were compared between encounters with specified and unspecified disease severity. Practices were divided into quartiles based on the proportion of clinical encounters with unspecified DR severity. Encounters with unspecified disease severity were associated with significantly older patient age, better visual acuity, and lower utilization of ophthalmic procedures. Higher volume practices and retina specialist practices had lower proportions of clinical encounters with unspecified disease severity. Results strongly suggest that DR disease severity related to ICD coding is missing not at random.

MYCOBACTERIUM ABSCESSUS SCLERAL BUCKLE INFECTION.

PURPOSE: To report the successful management of a rare case of Mycobacterium abscessus scleral buckle infection. METHODS: Case report. RESULTS: A 63-year-old woman with a history of sarcoid anterior uveitis and macula-off retinal detachment repaired by scleral buckle and pars plana vitrectomy presented with eye pain, redness, and purulent drainage in the left eye. Slit-lamp examination showed superonasal scleral buckle exposure, purulent conjunctival discharge, corneal edema, nongranulomatous keratic precipitates, and anterior chamber cell and flare. The patient underwent urgent scleral buckle removal. Intraoperatively, an area of scleral thinning without perforation underneath the exposed buckle was discovered and covered with a scleral patch graft, and an amniotic membrane graft was used to cover an area of bare sclera with significant conjunctival scarring and retraction. Cultures grew M. abscessus panresistant except to amikacin. After 6 weeks of fortified amikacin drops and a long taper of topical steroid therapy for persistent postoperative anterior uveitis, the patient's symptoms resolved. CONCLUSION: Mycobacterium is an emerging causative agent of scleral buckle infections. Our report provides insights about the management of such cases.

The effect of select systemic medications on outcomes in diabetics with central retinal vein occlusion.

BACKGROUND: Diabetes mellitus is a risk factor for central retinal vein occlusion (CRVO); however, it is unclear whether certain commonly used medications among diabetics or glycemic control impact visual outcomes in diabetic eyes with CRVO. PURPOSE: To evaluate the effect of select systemic medications and glycemic control on presenting features, treatment burden, and outcomes in patients with diabetes who develop a central retinal vein occlusion (CRVO). METHODS: Retrospective longitudinal cohort study at a single tertiary academic referral center from 2009-2017 investigating eyes of patients being treated for diabetes mellitus at CRVO onset. Eyes with a prior history of anti-vascular endothelial growth factor (anti-VEGF) therapy or laser treatment within the year prior to CRVO onset were excluded. Main outcomes and measures were visual acuity (VA), central subfield thickness (CST), cystoid macular edema (CME), and number of intravitreal injections and laser treatment throughout follow-up. RESULTS: We identified 138 eyes of 138 participants who were diabetic at CRVO onset. Of these, 49% had an ischemic CRVO. Median follow-up time was 25.5 months. Fifty-five eyes (40%) had a HbA1c within 6 months of CRVO presentation. HbA1c was positively correlated with both presenting CST (p = 0.04) and presence of CME (p < 0.01). In all 138 eyes, mean presenting VA was 20/246, and mean final VA was 20/364. Better-presenting VA was significantly associated with aspirin 325 mg use (p = 0.04). Lower CST at presentation was significantly associated with metformin use (p = 0.02). Sitagliptin use at CRVO onset was associated with a lower prevalence of CME at final follow-up (p < 0.01). Lower final CST was significantly associated with glipizide use at CRVO onset (p = 0.01). There were no significant associations between systemic medications or HbA1c and treatment burden or final VA (p > 0.05). CONCLUSION: Although aspirin 325 mg, metformin, sitagliptin, and glipizide were associated with better-presenting VA, lower-presenting CST, lower prevalence of macular edema at final visit, and lower final CST, respectively, none of these systemic agents or glycemic control were associated with decreased treatment burden or improved visual outcomes in diabetics with CRVO.

Systemic antiplatelet agents and anticoagulants in eyes with branch retinal vein occlusion.

PURPOSE: The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO). METHODS: A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded. RESULTS: A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents. CONCLUSION: Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit.

Healthcare disparities contribute to missed follow-up visits after cataract surgery in the USA: results from the perioperative care for intraocular lens study.

OBJECTIVE: To identify factors that contribute to missed cataract surgery follow-up visits, with an emphasis on socioeconomic and demographic factors. METHODS: In this retrospective cohort study, patients who underwent cataract extraction by phacoemulsification at Massachusetts Eye and Ear between 1 January and 31 December 2014 were reviewed. Second eye cases, remote and international patients, patients with foreign insurance and combined cataract cases were excluded. RESULTS: A total of 1931 cases were reviewed and 1089 cases, corresponding to 3267 scheduled postoperative visits, were included. Of these visits, 157 (4.8%) were missed. Three (0.3%) postoperative day 1, 40 (3.7%) postoperative week 1 and 114 (10.5%) postoperative month 1 visits were missed. Age<30 years (adjusted OR (aOR)=8.2, 95% CI 1.9 to 35.2) and ≥90 years (aOR=5.7, 95% CI 2.0 to 15.6) compared with patients aged 70-79 years, estimated travel time of >2 hours (aOR=3.2, 95% CI 1.4 to 7.4), smokers (aOR=2.7, 95% CI 1.6 to 4.8) and complications identified up to the postoperative visit (aOR=1.4, 95% CI 1.0 to 2.1) predicted a higher rate of missed visits. Ocular comorbidities (aOR=0.7, 95% CI 0.5 to 1.0) and previous visit best-corrected visual acuity (BCVA) of 20/50-20/80 (aOR=0.4, 95% CI 0.3 to 0.7) and 20/90-20/200 (aOR=0.4, 95% CI 0.2 to 0.9), compared with BCVA at the previous visit of 20/40 or better, predicted a lower rate of missed visits. Gender, race/ethnicity, language, education, income, insurance, alcohol use and season of the year were not associated with missed visits. CONCLUSIONS: Medical factors and demographic characteristics, including patient age and distance from the hospital, are associated with missed follow-up visits in cataract surgery. Additional studies are needed to identify disparities in cataract postoperative care that are population-specific. This information can contribute to the implementation of policies and interventions for addressing them.

Comparison of Modified Posterior Sub-Tenon's vs. Trans-Septal Triamcinolone Injection for Non-infectious Uveitis.

Purpose: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon's (PST) corticosteroid injections for noninfectious uveitis.Methods: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.Results: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7% vs 62.9%, p = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9% vs 9.0%, p = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.Conclusion: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.

Ocular Toxocariasis Presenting as Endophthalmitis in a Young Adult Intravenous Drug User.

Purpose: This report describes the diagnosis of ocular toxocariasis presenting as endophthalmitis in an adult intravenous drug user. Methods: A case is reported. Results: Fundus imaging showed numerous white opacities obscuring the macula. Toxocara canis serology was reactive with an enzyme immunoassay titer of 1:2 (positive ≥ 1:32). Findings from bacterial and fungal cultures were negative, and vitrectomy cytology revealed no organisms. Postoperatively, serial optical coherence tomography imaging demonstrated a slight decrease in size of an intraretinal hyperreflective lesion in the macula. Conclusions: Owing to a variety of presentations, ocular toxocariasis can be challenging to diagnose. In a patient with a history of intravenous drug use where fungal and bacterial organisms are more common causes of endophthalmitis, it is important to have a wide differential of causative organisms, particularly in the context of negative culture results and a worsening clinical examination.

Incidence of Management Changes at the Postoperative Day One Visit After Pars Plana Vitrectomy for Retinal Detachment.

PURPOSE: To evaluate the incidence of unexpected management changes on the first day after pars plana vitrectomy (PPV) for retinal detachment repair. DESIGN: Retrospective cohort study. METHODS: The medical and billing records of a large academic private practice were electronically queried for all cases of PPV for retinal detachment performed between January 1, 2017, and December 31, 2017. All cases of PPV for rhegmatogenous or tractional retinal detachment with completed postoperative day 1 (POD1) and postoperative week 1 (POW1) visits were included. The preoperative consultation, operative report, and POD1 and POW1 (postoperative days 5-14) visits were reviewed. Main outcome measures were incidence of unexpected management changes (change in or extended positioning, additional procedure, change in drop regimen, or shortened interval follow-up) at the POD1 visit after uncomplicated PPV for retinal detachment. RESULTS: Overall, 418 surgeries from 364 eyes and 355 patients were included. Eleven cases (2.6%) had an intraocular pressure (IOP) over 30 mm Hg at POD1. IOP-lowering drops were prescribed for 30 cases (7.2%). Silicone oil tamponade was positively associated with high IOP at POD1 (relative risk = 3.23, 95% confidence interval 0.96-10.84, P = 0.06). No additional management changes were made besides treating elevated IOP. CONCLUSIONS: Management changes on POD1 after vitrectomy for retinal detachment repair are relatively uncommon and were solely IOP related in this patient group. There may be flexibility regarding the type of POD1 encounter necessary, including an IOP check with an ophthalmic technician or non-retinal eye care provider. Larger, prospective studies are needed to better determine the most efficient follow-up routine.

Effect of ICD-9 to ICD-10 Transition on Accuracy of Codes for Stage of Diabetic Retinopathy and Related Complications: Results from the CODER Study.

PURPOSE: When the International Classification of Diseases 9th Revision (ICD-9) transitioned to the International Classification of Diseases 10th Revision (ICD-10), there was a marked increase in the complexity of International Classification of Diseases (ICD) codes with potential for improved specificity in clinical database research. The purpose of this study was to characterize the accuracy of coding for stage of diabetic retinopathy (DR) and DR-related complications (including vitreous hemorrhage, retinal detachment, and neovascular glaucoma) during this transition. DESIGN: Retrospective chart review of 3 time periods corresponding to the use of ICD-9: 2014-2015; "early" use of ICD-10, 2015-2016; and "late" use of ICD-10, 2018-2019. PARTICIPANTS: Patients aged 18 years or older with a diagnosis of DR at a multispecialty academic institution. METHODS: Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and kappa (κ) statistics were generated for each diagnosis. Generalized estimating equation (GEE) models were used to assess the significance of the variables. MAIN OUTCOME MEASURE: The main outcome was the proportion of agreement between the ICD code and the documented chart standard for stage of DR and DR-related complications. RESULTS: A total of 600 patients were included in the study (average age, 61 years; range, 25-93 years). Overall, there was substantial agreement between the ICD codes for stage of DR and the documented standard (κ = 0.66). The proportion of ICD codes in agreement with the documented standard diagnosis increased with time: 66.5%, 78.5%, and 83.3% for ICD-9, "early" ICD-10, and "late" ICD-10, respectively. The odds of agreement were 2.67 (95% confidence interval [CI], 1.49-4.76, P < 0.001) and 3.96 (95% CI, 2.34-6.69, P < 0.0001) times greater for "early" and "late" ICD-10 codes compared with ICD-9 codes, respectively. For specific codes, the overall PPV, NPV, sensitivity, and specificity for nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were excellent (>90%). The odds of agreement were 19.70 (95% CI, 11.54-33.64, P < 0.0001) times greater for PDR than NPDR. Compared with the stage of DR, DR-related diagnoses were overall less accurately coded (κ = 0.61, 0.48, and 0.52 for vitreous hemorrhage, retinal detachment, and neovascular glaucoma, respectively). CONCLUSIONS: Coding in ICD-10 is more accurate than in ICD-9, particularly for PDR compared with NPDR. The increased accuracy emphasizes the potential for ICD-10 coding to be used effectively in database research.

Quantifying the educational benefit of additional cataract surgery cases in ophthalmology residency.

PURPOSE: To quantify the resident learning curve for cataract surgery using operative time as an indicator of surgical competency, to identify the case threshold at which marginal additional educational benefit became equivocal, and to characterize heterogeneity in residents' pathways to surgical competency. SETTING: Academic medical center. DESIGN: Large-scale retrospective consecutive case series. METHODS: All cataract surgery cases performed by resident physicians as primary surgeon at Massachusetts Eye and Ear from July 1, 2010, through June 30, 2015, were reviewed. Data were abstracted from Accreditation Council for Graduate Medical Education case logs and operative time measurements. A linear mixed-methods analysis was conducted to model changes in residents' cataract surgery operative times as a function of sequential case number, with resident identity included as a random effect in the model to normalize between-resident variability. RESULTS: A total of 2096 cases were analyzed. A marked progressive decrease in operative time was noted for resident cases 1 to 39 (mean change -0.17 minutes per additional case, 95% CI, -0.21 to -0.12; P < .001). A modest, steady reduction in operative time was subsequently noted for case numbers 40 to 149 (mean change -0.05 minutes per additional case, 95% CI, -0.07 to -0.04; P < .001). No statistically significant improvement was found in operative times beyond the 150th case. CONCLUSIONS: Residents derived educational benefit from performing a greater number of cataract procedures than current minimum requirements. However, cases far in excess of this threshold might have diminishing educational return in residency. Educational resources currently used for these cases might be more appropriately devoted to other training priorities.

Clinical factors affecting operating room utilization in cataract surgery: Results from the PCIOL study.

PURPOSE: To identify preoperative clinical characteristics affecting cataract surgery operative time. SETTING: Academic center. DESIGN: Large-scale retrospective cohort study. METHODS: All cases of cataract extraction by phacoemulsification and intraocular lens insertion performed by Comprehensive Ophthalmology at Massachusetts Eye and Ear between January 1, 2014, and December 31, 2014, were reviewed. Clinically relevant predictors of operative time were identified a priori, and a multivariate analysis was used to identify which predictors were associated with operative time. To quantify the surgeon effect, 2 regression models were built, one inclusive of surgeon identity and the other with years of experience and the training level of the supervised resident instead of identity. RESULTS: Overall, 1349 cataract surgeries in 1072 patients were included. The mean operative time was 22.1 ± 7.8 minutes. Multiple clinical factors were significantly associated with operative time, with attending surgeon identity being the most important. In the multivariate model with surgeon identity, longer operative time was associated with male sex, increased body mass index, first-eye surgery, left operative eye, advanced cataract, use of iris hooks, use of Malyugin ring, use of trypan blue, history of diabetic retinopathy, short axial length, and shallow anterior chamber depth. The R value for the model inclusive of attending identity was 0.42, significantly higher than the R value of 0.23 for the model exclusive of identity. CONCLUSION: Preoperative clinical characteristics, such as patient demographics, biometry data, and cataract severity, significantly correlate with operative time. Surgeon identity is highly correlated with operative time. Incorporating these results into predictive algorithms may allow for more predictable surgical scheduling and more efficient use of operative resources.

Optimization of cataract surgery follow-up: A standard set of questions can predict unexpected management changes at postoperative week one.

PURPOSE: There is limited evidence to inform the optimal follow-up schedule after cataract surgery. This study aims to determine whether a standardized question set can predict unexpected management changes (UMCs) at the postoperative week one (POW1) timepoint. SETTING: Massachusetts Eye and Ear, Harvard Medical School. DESIGN: Prospective cohort study. METHODS: Two-hundred-and-fifty-four consecutive phacoemulsification cases having attended an examination between postoperative days 5-14. A set of 7 'Yes' or 'No' questions were administered to all participants by a technician at the POW1 visit. Patient answers along with perioperative patient information were recorded and analyzed. Outcomes were the incidence of UMCs at POW1. RESULTS: The incidence of UMCs was zero in uneventful cataract cases with unremarkable history and normal postoperative day one exam if no positive answers were given with the question set demonstrating 100% sensitivity (p<0.0001). A test version with 5 questions was equally sensitive in detecting UMCs at POW1 after cataract surgery. CONCLUSION: In routine cataract cases with no positive answers to the current set of clinical questions, a POW1 visit is unlikely to result in a management change. This result offers the opportunity for eye care providers to risk-stratify patients who have had cataract surgery and individualize follow-up.