Feeding-dependent VIP neuron-ILC3 circuit regulates the intestinal barrier.

The intestinal mucosa serves both as a conduit for the uptake of food-derived nutrients and microbiome-derived metabolites, and as a barrier that prevents tissue invasion by microorganisms and tempers inflammatory responses to the myriad contents of the lumen. How the intestine coordinates physiological and immune responses to food consumption to optimize nutrient uptake while maintaining barrier functions remains unclear. Here we show in mice how a gut neuronal signal triggered by food intake is integrated with intestinal antimicrobial and metabolic responses that are controlled by type-3 innate lymphoid cells (ILC3)1-3. Food consumption rapidly activates a population of enteric neurons that express vasoactive intestinal peptide (VIP)4. Projections of VIP-producing neurons (VIPergic neurons) in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIP receptor type 2 (VIPR2; also known as VPAC2). Production of interleukin (IL)-22 by ILC3, which is upregulated by the presence of commensal microorganisms such as segmented filamentous bacteria5-7, is inhibited upon engagement of VIPR2. As a consequence, levels of antimicrobial peptide derived from epithelial cells are reduced but the expression of lipid-binding proteins and transporters is increased8. During food consumption, the activation of VIPergic neurons thus enhances the growth of segmented filamentous bacteria associated with the epithelium, and increases lipid absorption. Our results reveal a feeding- and circadian-regulated dynamic neuroimmune circuit in the intestine that promotes a trade-off between innate immune protection mediated by IL-22 and the efficiency of nutrient absorption. Modulation of this pathway may therefore be effective for enhancing resistance to enteropathogens2,3,9 and for the treatment of metabolic diseases.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques.

Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication and could be enhanced by substituting naturally occurring simian immunodeficiency virus Env residues at position 375, which resides at a critical location in the CD4-binding pocket and is under strong positive evolutionary pressure across the broad spectrum of primate lentiviruses. SHIVs containing primary or transmitted/founder HIV-1 subtype A, B, C, or D Envs with genotypic variants at residue 375 were constructed and analyzed in vitro and in vivo. Bulky hydrophobic or basic amino acids substituted for serine-375 enhanced Env affinity for rhCD4, virus entry into cells bearing rhCD4, and virus replication in primary rhCD4 T cells without appreciably affecting antigenicity or antibody-mediated neutralization sensitivity. Twenty-four RMs inoculated with subtype A, B, C, or D SHIVs all became productively infected with different Env375 variants-S, M, Y, H, W, or F-that were differentially selected in different Env backbones. Notably, SHIVs replicated persistently at titers comparable to HIV-1 in humans and elicited autologous neutralizing antibody responses typical of HIV-1. Seven animals succumbed to AIDS. These findings identify Env-rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors.

Effect of Prior Anti-VEGF Injections on the Risk of Retained Lens Fragments and Endophthalmitis after Cataract Surgery in the Elderly.

PURPOSE: To investigate the effect of prior intravitreal anti-vascular endothelial growth factor (VEGF) injections on surgical and postoperative complication rates associated with cataract surgery in a nationally representative longitudinal sample of elderly persons. DESIGN: Retrospective, longitudinal cohort analysis. PARTICIPANTS: A total of 203 643 Medicare beneficiaries who underwent cataract surgery from January 1, 2009, to December 31, 2013. METHODS: By using the 5% sample of Medicare claims data, the study assessed risks of 3 adverse outcomes after receipt of cataract surgery for beneficiaries with a history of intravitreal injections. Risks of these outcomes in beneficiaries with a history of intravitreal injections relative to those without were calculated using the Cox proportional hazard model. MAIN OUTCOME MEASURES: The primary outcome was the risk of subsequent removal of retained lens fragments (RLFs) within 28 days after cataract surgery. Secondary outcomes were a new diagnosis of acute (<40 days) or delayed-onset (40+ days) endophthalmitis and risk of a new primary open-angle glaucoma (POAG) diagnosis within 365 days after cataract surgery. RESULTS: Prior intravitreal anti-VEGF injections were associated with a significantly increased risk of subsequent RLF removal within 28 days after cataract surgery (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.19-4.30). Prior injections were also associated with increased risk of both acute (HR, 2.29; 95% CI, 1.001-5.22) and delayed-onset endophthalmitis (HR, 3.65; 95% CI, 1.65-8.05). Prior injections were not a significant indicator of increased risk of a new POAG diagnosis. CONCLUSIONS: A history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications and endophthalmitis. Given the frequency of intravitreal injections and cataract surgery, increased preoperative assessment, additional intraoperative caution, and postoperative vigilance are recommended in patients with a history of intravitreal injections undergoing cataract extraction.

Introducing Anti-Vascular Endothelial Growth Factor Therapies for AMD Did Not Raise Risk of Myocardial Infarction, Stroke, and Death.

PURPOSE: To assess the effect of availability of anti-vascular endothelial growth factor (VEGF) therapy on mortality and hospitalizations for acute myocardial infarction (AMI) and stroke over a 5-year follow-up period in United States Medicare beneficiaries newly diagnosed with exudative age-related macular degeneration (AMD) in 2006 compared with control groups consisting of beneficiaries (1) newly diagnosed with exudative AMD at a time when anti-VEGF therapy was not possible and (2) newly diagnosed with nonexudative AMD. DESIGN: Retrospective cohort study. PARTICIPANTS: Beneficiaries newly diagnosed with exudative and nonexudative AMD in 2000 and 2006 selected from a random longitudinal sample of Medicare 5% claims and enrollment files. METHODS: Beneficiaries with a first diagnosis of exudative AMD in 2006 were the treatment group; beneficiaries newly diagnosed with exudative AMD in 2000 or nonexudative AMD in 2000 or 2006 were control groups. To deal with potential selection bias, we designed an intent-to-treat study, which controlled for nonadherence to prescribed regimens. The treatment group consisted of patients with clinically appropriate characteristics to receive anti-VEGF injections given that the therapy is available, bypassing the need to monitor whether treatment was actually received. Control groups consisted of patients with clinically appropriate characteristics but first diagnosed at a time when the therapy was unavailable (2000) and similar patients but for whom the therapy was not clinically indicated (2000, 2006). We used a Cox proportional hazard model. MAIN OUTCOME MEASURES: All-cause mortality and hospitalization for AMI and stroke during follow-up. RESULTS: No statistically significant changes in probabilities of death and hospitalizations for AMI and stroke within a 5-year follow-up period were identified in exudative AMD beneficiaries newly diagnosed in 2006, the beginning of widespread anti-VEGF use, compared with 2000. As an alternative to our main analysis, which excluded beneficiaries from nonexudative AMD group who received anti-VEGF therapies during follow-up, we performed a sensitivity analysis with this group of individuals reincluded (11% of beneficiaries newly diagnosed with nonexudative AMD in 2006). Results were similar. CONCLUSIONS: Introduction of anti-VEGF agents in 2006 for treating exudative AMD has not posed a threat of increased risk of AMI, stroke, or all-cause mortality.

SMALL-GAUGE VALVED VERSUS NONVALVED CANNULA PARS PLANA VITRECTOMY FOR RETINAL DETACHMENT REPAIR.

PURPOSE: To compare functional and anatomical outcomes and complication rates between valved versus traditional nonvalved small-gauge cannula vitrectomy for retinal detachment repair. METHODS: Retrospective case series of 163 eyes undergoing small-gauge valved versus nonvalved vitrectomy with intraoperative perfluoro-n-octane for retinal detachment repair at a single academic institution. RESULTS: There were 104 eyes in the valved cannula group and 59 eyes in the nonvalved cannula group. The valved group had lower baseline Grade C proliferative vitreoretinopathy (35 vs. 53%, P = 0.031) and combined rhegmatogenous retinal detachment/tractional retinal detachment (3 vs. 12%, P = 0.037), but both groups had otherwise comparable preoperative characteristics. Final postoperative best-corrected visual acuity was 1.01 logarithm of the minimum angle of resolution (Snellen 20/205) and 1.27 (Snellen 20/372) (P = 0.131) in valved and nonvalved cannula eyes, respectively. Single surgery success was equivalent between the valved and nonvalved groups (88 vs. 86%; P = 1.00). Final anatomical success was higher in the valved versus nonvalved group (98 vs. 90%; P = 0.027). Complication rates were not statistically different, including Postoperative Day 1 intraocular pressure, Postoperative Day 1 anterior chamber fibrin, retained subretinal/intraocular perfluoro-n-octane, and epiretinal membrane peeling. CONCLUSION: Valved cannulas, with their improved fluidics, are an important addition to pars plana vitrectomy with similar functional and anatomical success without increased complication rates compared with traditional nonvalved cannulas.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

INTRAOPERATIVE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING AFTER INTERNAL LIMITING MEMBRANE PEELING IN IDIOPATHIC EPIRETINAL MEMBRANE WITH CONNECTING STRANDS.

PURPOSE: To report the intraoperative optical coherence tomography findings in idiopathic epiretinal membrane (ERM) with connecting strands and to describe the postoperative outcomes. METHODS: A retrospective, case series study within a prospective observational intraoperative optical coherence tomography imaging study was performed. Epiretinal membranes with connecting strands were characterized on preoperative spectral domain optical coherence tomography images and assessed against corresponding intraoperative (after internal limiting membrane [ILM] peeling) and postoperative spectral domain optical coherence tomography images. RESULTS: Eleven locations of the connecting strands in 7 eyes were studied. The connecting strands had visible connections from the inner retinal surface to the ERM in all locations, and the reflectivity was moderate in 8 locations and high in 3 locations. After ERM and ILM peeling, disconnected strands were identified in all of the intraoperative optical coherence tomography images. The reflectivity of the remaining intraoperative strands was higher than that of the preoperative lesions and appeared as "finger-like" and branching projections. The remaining disconnected lesions were contiguous with the inner retinal layers. Postoperatively, the intraoperative lesions disappeared completely in all locations, and recurrent formation of ERM was not identified in any eyes. CONCLUSION: In ERM eyes with connecting strands, intraoperative spectral domain optical coherence tomography imaging showed moderately to highly reflective sub-ILM finger-like lesions that persist immediately after membrane and ILM peeling. Postoperatively, the hyperreflective lesions disappeared spontaneously without localized nerve fiber layer loss. The sub-ILM connecting strands may represent glial retinal attachments.

SAFETY PROFILE OF OCRIPLASMIN FOR SYMPTOMATIC VITREOMACULAR ADHESION: A Comprehensive Analysis of Premarketing and Postmarketing Experiences.

PURPOSE: After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. METHODS: Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. RESULTS: Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. CONCLUSION: Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.

Closing the loop for AI-ready radiology.

BACKGROUND: In recent years, AI has made significant advancements in medical diagnosis and prognosis. However, the incorporation of AI into clinical practice is still challenging and under-appreciated. We aim to demonstrate a possible vertical integration approach to close the loop for AI-ready radiology. METHOD: This study highlights the importance of two-way communication for AI-assisted radiology. As a key part of the methodology, it demonstrates the integration of AI systems into clinical practice with structured reports and AI visualization, giving more insight into the AI system. By integrating cooperative lifelong learning into the AI system, we ensure the long-term effectiveness of the AI system, while keeping the radiologist in the loop.  RESULTS: We demonstrate the use of lifelong learning for AI systems by incorporating AI visualization and structured reports. We evaluate Memory Aware-Synapses and Rehearsal approach and find that both approaches work in practice. Furthermore, we see the advantage of lifelong learning algorithms that do not require the storing or maintaining of samples from previous datasets. CONCLUSION: In conclusion, incorporating AI into the clinical routine of radiology requires a two-way communication approach and seamless integration of the AI system, which we achieve with structured reports and visualization of the insight gained by the model. Closing the loop for radiology leads to successful integration, enabling lifelong learning for the AI system, which is crucial for sustainable long-term performance. KEY POINTS: · The integration of AI systems into the clinical routine with structured reports and AI visualization.. · Two-way communication between AI and radiologists is necessary to enable AI that keeps the radiologist in the loop.. · Closing the loop enables lifelong learning, which is crucial for long-term, high-performing AI in radiology..

Unprocessed real-time imaging of vitreoretinal surgical maneuvers using a microscope-integrated spectral-domain optical coherence tomography system.

BACKGROUND: We have recently developed a microscope-integrated spectral-domain optical coherence tomography (MIOCT) device towards intrasurgical cross-sectional imaging of surgical maneuvers. In this report, we explore the capability of MIOCT to acquire real-time video imaging of vitreoretinal surgical maneuvers without post-processing modifications. METHODS: Standard 3-port vitrectomy was performed in human during scheduled surgery as well as in cadaveric porcine eyes. MIOCT imaging of human subjects was performed in healthy normal volunteers and intraoperatively at a normal pause immediately following surgical manipulations, under an Institutional Review Board-approved protocol, with informed consent from all subjects. Video MIOCT imaging of live surgical manipulations was performed in cadaveric porcine eyes by carefully aligning B-scans with instrument orientation and movement. Inverted imaging was performed by lengthening of the reference arm to a position beyond the choroid. RESULTS: Unprocessed MIOCT imaging was successfully obtained in healthy human volunteers and in human patients undergoing surgery, with visualization of post-surgical changes in unprocessed single B-scans. Real-time, unprocessed MIOCT video imaging was successfully obtained in cadaveric porcine eyes during brushing of the retina with the Tano scraper, peeling of superficial retinal tissue with intraocular forceps, and separation of the posterior hyaloid face. Real-time inverted imaging enabled imaging without complex conjugate artifacts. CONCLUSIONS: MIOCT is capable of unprocessed imaging of the macula in human patients undergoing surgery and of unprocessed, real-time, video imaging of surgical maneuvers in model eyes. These capabilities represent an important step towards development of MIOCT for efficient, real-time imaging of manipulations during human surgery.

Ten-year incidence of age-related macular degeneration according to diabetic retinopathy classification among medicare beneficiaries.

PURPOSE: To compare the longitudinal incidence over 10 years of dry and wet age-related macular degeneration (AMD) in a U.S. sample of Medicare beneficiaries with no diabetes mellitus, diabetes mellitus without retinopathy, nonproliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). METHODS: Using Medicare claims data, the 10-year incidence of dry and wet AMD from 1995 to 2005 in beneficiaries older than 69 years with newly diagnosed diabetes mellitus (n = 6,621), NPDR (n = 1,307), and PDR (n = 327) compared with each other and matched controls without diabetes for each group. RESULTS: After controlling for covariates, newly diagnosed NPDR was associated with significantly increased risk of incident diagnosis of dry AMD (hazard ratio, 1.24; 95% confidence interval: 1.08-1.43) and wet AMD (hazard ratio 1.68; 95% confidence interval: 1.23-2.31). Newly diagnosed PDR was associated with significantly increased risk of wet AMD only (hazard ratio 2.15; 95% confidence interval: 1.07-4.33). Diabetes without retinopathy did not affect risk of dry or wet AMD. There was no difference in risk of wet AMD in PDR compared with NPDR. CONCLUSION: Elderly individuals with NPDR or PDR may be at higher risk of AMD compared to those without diabetes mellitus or diabetic retinopathy.

Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device.

PURPOSE: The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from preclinical testing into human intraoperative imaging. METHODS: Before human imaging, surgical conditions were fully simulated for extensive preclinical MIOCT evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. RESULTS: Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The preclinical evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. CONCLUSION: This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.

Evolving Treatment Patterns in Diabetic Macular Edema Between 2015 and 2020.

Purpose: To explore the recent evolution of diabetic macular edema (DME) treatment practice patterns over 5 years among retina specialists in the United States. Methods: This retrospective analysis assessed 306 700 eyes with newly diagnosed DME from the Vestrum Health database between January 2015 and October 2020. The year-over-year and cumulative 5-year distributions of eyes treated with antivascular endothelial growth factor (anti-VEGF) agents, steroids, focal laser, or any combination and those of untreated eyes were calculated. Changes from baseline visual acuity were assessed. Results: Yearly treatment patterns changed significantly from 2015 (n = 18056) to 2020 (n = 11042). The proportion of untreated patients declined over time (32.7% vs 27.7%; P < .001), the use of anti-VEGF monotherapy increased (43.5% vs 61.8%; P < .001), the use of focal laser monotherapy declined (9.7% vs 3.0%; P < .001), and the use of steroid monotherapy remained stable (0.9% vs 0.7%; P = 1.000). Of eyes that maintained follow-up for 5 years (from 2015 to 2020), 16.3% were untreated while 77.5% were treated with anti-VEGF agents (as monotherapy or combination therapy). Vision gains in treated patients remained approximately stable from 2015 (3.6 letters) to 2020 (3.5 letters). Conclusions: From 2015 to 2020, treatment patterns for DME evolved toward greater anti-VEGF monotherapy, stable steroid monotherapy, less laser monotherapy, and fewer untreated eyes.

The Broader Economic Value of Treatment for Diabetic Macular Edema.

OBJECTIVE: To simulate economic outcomes for individuals with diabetic macular edema (DME) and estimate the economic value of direct and indirect benefits associated with DME treatment. RESEARCH DESIGN AND METHODS: Our study pairs individual and cohort analyses to demonstrate the value of treatment for DME. We used a microsimulation model to simulate self-reported vision (SRV) and economic outcomes for individuals with DME. Four scenarios derived from clinical trial data were simulated and compared for a lifetime horizon: untreated, anti-VEGF therapy, laser, and steroid. To quantify the relative magnitude of costs and benefits of DME treatment in the U.S., we used a cohort-level analysis based on real-world treatment parameters derived from published data. RESULTS: In the model, excellent/good SRV roughly corresponded to 20/40 or better visual acuity. A representative 51-year-old treated for DME would spend 30-35% additional years with excellent/good SRV and 29-32% fewer years with fair/poor SRV relative to being untreated. A treated individual would experience 4-5% greater life expectancy and 9-13% more quality-adjusted life-years. Indirect benefits from treatment included 6-9% more years working, 12-19% greater lifetime earnings, and 8-16% fewer years with disability. For the U.S. DME cohort (1.1. million people), total direct benefit was $63.0 billion over 20 years, and total indirect benefit was $4.8 billion. Net value (benefit - cost) of treatment ranged from $28.1 billion to $52.8 billion. CONCLUSIONS: Treatment for DME provides economic value to patients and society through improved vision, life expectancy, and quality of life and indirectly through improved employment and disability outcomes.

Opportunity Cost of Vitreoretinal Surgeries.

Purpose: To compare physician reimbursements for vitreoretinal surgeries with office-based patient care. Methods: A theoretical model was performed comparing physician work reimbursements for the 10 most common vitreoretinal surgeries with office-based work relative value units (wRVUs) that could have been generated during the same global time period. The reference physician was modeled at 40 patients per 8-hour workday. A lower volume physician and higher volume physician were modeled at 30 patients/day and 50 patients/day, respectively. The reimbursement rates and allocated times for surgery were based on the 2021 values set by Medicare, and the average wRVU per office visit was based on 2021 real-world data from the Vestrum Retinal Healthcare Database. Results: In the reference case, performing any of the 10 most common vitreoretinal surgeries was associated with an opportunity cost with a weighted mean of 49% (range, 40%-68%) relative to lost office productivity. The Centers for Medicare & Medicaid Services (CMS) allocated a weighted mean intraservice time of 73 minutes; however, the reference physician would have to complete the surgery with a weighted average of 5 minutes (range, -31-12 minutes) for surgical wRVUs to equal office-based reimbursements. Performing these 10 surgeries was associated with a 25% opportunity cost even for the lower volume physician and 61% for the higher volume physician. Probability sensitivity analysis with a range of conditions identified opportunity costs from surgery in over 99% of simulated scenarios. Conclusions: Medicare reimbursements for the physician work component of vitreoretinal surgeries represented a significant opportunity cost for the physician relative to office-based patient care of equivalent time, especially for busier physicians. The model did not explore practice overhead and professional liability insurance, which are factored separately by CMS and may influence the opportunity cost depending on utilization. The average threshold surgery times for surgical reimbursements to equal office-based reimbursements may be difficult to achieve.

Best practices for treatment of retinal vein occlusion.

PURPOSE OF REVIEW: Retinal vein occlusion (RVO) is a sight-threatening retinal vascular disorder associated with macular edema and neovascularization. Until recently, the standard of care for branch RVO-associated macular edema was grid laser photocoagulation and observation for central RVO-associated macular edema. Neovascularization was treated with scatter laser photocoagulation. The purpose of this article is to review recent findings that have changed our treatments of RVO. RECENT FINDINGS: The recent development of intravitreal pharmacotherapy has demonstrated benefit with anti-vascular endothelial growth factor (VEGF) agents and corticosteroids for the treatment of RVO-associated macular edema. The intravitreal use of FDA-approved ranibizumab (Lucentis) and a sustained release dexamethasone implant (Ozurdex), along with off-label bevacizumab (Avastin) and preservative-free triamcinolone, has significantly expanded our treatment options and replaced standard of care for treatment of RVO-associated macular edema. Whereas anti-VEGF agents can also induce rapid regression of neovascularization, scatter laser photocoagulation remains the standard of care to prevent neovascular complications. SUMMARY: Intravitreal pharmacotherapy has revolutionized our treatment of retinal vascular diseases, including RVO. Although these intravitreal agents are effective, our understanding of their specific indications and long-term roles is still evolving. Furthermore, until the underlying occlusive pathophysiology of RVO can be addressed, our treatments will be limited to temporizing therapies against a chronic disease.

The Impact of COVID-19 on US and International Retina Specialists, Their Practices, and Their Patients.

Purpose: This work analyzes data from a series of surveys developed by the American Society of Retina Specialists (ASRS) that assesses the impact of COVID-19 on physicians, their practices, and their patients. Methods: Five surveys were sent by the ASRS between March and July 2020 to more than 2600 US and international retina specialists. Data and trends from these surveys were analyzed. Results: Most responding retina specialists (87%-95% in the United States and internationally) reported having no known COVID-related symptoms despite reported limitations in personal protective equipment. Clinic volumes globally were drastically reduced in March 2020 with only partial recovery through July 2020, which was slower internationally than in the United States. Practices were compelled to reduce staff and physician employment levels. Most respondents estimated some degree of delay in patient treatment with corresponding declines in vision and/or anatomy that were attributed most frequently to patients' fears of the pandemic and least frequently to office unavailability. Conclusions: The reported impact of COVID-19 on retina specialists, their practices, and their patients has been substantial. Although retina specialists were quickly resilient in optimizing delivery of patient care in a manner safe for patients and providers, the reduction in clinic volume has been devastating in the United States and internationally, with negative impacts on patient outcomes, reductions in practices' volume and employment, and risk to practices' financial health. Future studies will be required to quantify losses associated with these unprecedented and ongoing circumstances caused by the pandemic.

Opportunity Cost of Retinal Detachment Surgery vs Office-Based Patient Care.

Purpose: This work compares physician reimbursements for retinal detachment (RD) surgery with office-based patient care. Methods: A theoretical model was constructed from the physician's perspective for performing a 90-minute uncomplicated RD surgery with its associated perioperative work in the global period (Current Procedural Terminology code 67108) compared with managing 40 patients per 8-hour clinic day in the equivalent time period. The reimbursement rates were based on the 2019 values set by the US Centers for Medicare and Medicaid Services (CMS). Sensitivity analyses were performed varying the perioperative times, clinical productivity, and postoperative visits. Results: The CMS physician reimbursement rate for 67108 surgery was 17.13 work relative value units (wRVUs); meanwhile, the physician in the reference case could have generated 40.89 wRVUs in the office. CMS reimbursement therefore represented a 58% opportunity cost relative to lost office productivity for the physician. A significant disparity was still present even when modeling 30 patients per day. In sensitivity analyses, clinical productivity exceeded surgical compensation in 99% of modeled scenarios. In threshold analyses, the surgeon in the reference case would have to complete the surgery and all immediate perioperative care within 18 minutes to equal the total CMS valuation. Conclusions: CMS reimbursement for RD surgery resulted in a significant opportunity cost for the physician relative to office-based patient care, which was more pronounced for more efficient clinicians in the office. The sensitivity analyses supported the robustness of the model. Reductions in surgery reimbursements relative to office-based patient care might disincentivize busy clinicians.