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.

Trends and Pattern of Diseases Under Integrated Disease Surveillance Project in Jodhpur, Rajasthan: A Retrospective Observational Study.

Background: Progress of the Integrated Disease Surveillance (IDSP) is of utmost importance to ensure optimal performance in Jodhpur, Rajasthan, India. The purpose of the study was to document the physical performance of the surveillance system on its core and support functions. Material and Methods: Mixed method study was conducted between September 2020 to October 2020. Quantitative data was collected from the district IDSP unit of the Chief Medical and Health Office (CMHO) for various blocks of Rajasthan using syndromic, presumptive, and laboratory-confirmed reporting formats. Ethical clearance was obtained from the Institutional Ethical Committee of AIIMS, Jodhpur. Results: Rajasthan reported outbreaks between 0.55 to 1.2% of the national average between 2015-2019. Acute respiratory infections, fever of unknown origin, and acute diarrhea were the leading diseases under the presumptive reporting format. Major syndromic cases reported were cough with/without fever (more than three weeks) and fever less than seven days with the rash. Laboratory-confirmed Dengue, Malaria, and hepatitis were reported more in urban Jodhpur. Conclusion: Despite some pitfalls, IDSP has made satisfactory improvements in its core and support functions in the Jodhpur district of Rajasthan. The number of preventable morbidity and mortality cases associated with notifiable infectious diseases in our country can be effectively countered by strengthening the IDSP reporting system.

Pulmonary Tuberculosis Presenting As Septic Shock in an Immunocompetent Patient: Revisiting an Old Disease With New Perspectives.

Septic shock due to Mycobacterium tuberculosis (M. tuberculosis) in immunocompromised patients (particularly HIV) is a well-recognized clinical entity. However, tubercular sepsis in the immunocompetent is still underdiagnosed and under-discussed. Moreover, sepsis is usually associated with gram-negative and other gram-positive microorganisms that can cause similar pulmonary and disseminated disease and can further convolute the diagnosis. We herein discuss a case of an elderly female who presented with acute onset fever, cough, and altered talk from the last seven days. Her initial clinical and laboratory examination revealed features of lower respiratory tract infection with septic shock. She was started on broad-spectrum antibiotics based on severe community-acquired pneumonia management guidelines. Her blood and urine cultures were sterile. She did not respond to initial antibiotics. Furthermore, sputum production was not possible, which compelled us for gastric aspirate analysis, which came positive for cartridge-based nucleic acid amplification test (CBNAAT). In repeated blood cultures, M. tuberculosis was also isolated. She was started on antitubercular treatment; on the 12th day of antitubercular treatment, she developed acute respiratory distress and eventually succumbed to her illness on the 19th day of hospitalization. We highlighted the importance of early diagnosis and prompt antitubercular therapy in tubercular septic shock. We also discuss the possibility of tubercular-immune reconstitution inflammatory syndrome (IRIS) in such patients, which could be a contributing factor to mortality.

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.

Preparedness for managing pandemic using distributed mobile brokers - Using COVID 19 use case.

The human community has experienced the worst disaster during this pandemic spread of COVID-19. Getting essential services viz., medical, food, water, and oxygen support have been challenging during the pandemic. People suffer inadequate essential services during these lockdowns and quarantines. This paper proposes a distributed mobile broker service using the MQTT protocol for managing and accessing essential services during a pandemic. The proposed method splits the city into areas. The essential service providers register their services with the publishers and the essential service seekers seek their services from the publishers using mobile brokers. The mobile broker is also equipped with data aware trajectory planning technique that considers collecting data from available nodes with less delay. The proposed technique has been tested under two scenarios viz., mobile brokers, fixed subscribers, and mobile brokers, mobile subscribers. The performance analysis has been carried out in terms of delay and packet delivery ratio with fixed broker conditions.

Right Atrial Thrombus in a Patient of Rheumatic Heart Disease with Severe Mitral Regurgitation: A Rare Association.

BACKGROUND: Right atrial thrombus is a rare phenomenon, and its incidence is not well- defined. It usually occurs in the presence of predisposing factors like tricuspid stenosis or following central venous catheterization. Isolated right atrial thrombus without any predisposing factors occurs rarely. CASE PRESENTATION: We herein report a 30-year-old male patient, a known case of rheumatic heart disease with mitral regurgitation, presented with severe breathlessness and orthopnea. He was diagnosed with acute pulmonary oedema with biventricular dysfunction and congestive symptoms. On transthoracic 2D echocardiography, he was found to have severe mitral and severe tricuspid regurgitation. All cardiac chambers were dilated, and an incidental finding of right atrial thrombus was noted. Patient The patient was managed conservatively, but he succumbed to his worsening heart failure. CONCLUSION: Treating physicians should be aware of the possibility of right atrial thrombus in rheumatic mitral valve disease because of its clinical implications, like life life-threatening pulmonary embolization and need of surgical management.

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.

Post-Discharge Prophylactic Anticoagulation in COVID-19 Patients: A Clinical Dilemma.

BACKGROUND: COVID-19 pandemic has taken a great toll on the health care system worldwide. Along with the pandemic, there is also a concern regarding post COVID-19 complications in recovered patients. Thromboembolism (TE) has been reported as a fatal complication in recovered patients with COVID-19. There is still a great dilemma in post-discharge TE prophylaxis and its long-term benefits. CASE DESCRIPTION: We reported three cases of post COVID-19 with complications related to both diseases as well as post discharge anticoagulant therapy. The first case is about a 60-yr-old male who developed Covid-19 pneumonia (moderate disease) and was discharged on rivaroxaban after initial improvement. 3 weeks later, the patient was readmitted with lower gastro-intestinal bleeding. The other two cases developed pulmonary thromboembolism within a span of 2-3 months (after recovered from COVID-19 pneumonia). Both these patients were not prescribed anticoagulants for TE prophylaxis. CONCLUSION: There is an imperative need for effective guidelines for post discharge TE prophylaxis in COVID-19.

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.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up Risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India: A Prospective Cohort Study.

OBJECTIVE: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and preemptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. METHOD AND MATERIALS: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. RESULTS: A total of 116 patients were analyzed. Asymptomatic cryptococcal antigenemia was detected in 5.17% of patients and is correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. CONCLUSION: Serum cryptococcal antigen positivity is correlated with an increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

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.