Cost Analysis of Dropless Cataract Surgery Prophylaxis with Intracameral Antibiotics and Subconjunctival Steroids.

PURPOSE: To determine whether dropless, injection-based cataract surgery prophylaxis with intracameral antibiotic and subconjunctival steroid may reduce healthcare system costs and patient out-of-pocket costs compared to topical medication regimens. SETTING: United States national medical expenditures database. DESIGN: Retrospective cost analysis. METHODS: Costs were analyzed for topical ophthalmics from the 2020 Medical Expenditure Panel Survey (MEPS) and for dropless medications from pharmaceutical invoices/catalogs. Main outcomes included system costs, from insurance and patient payments, and out-of-pocket costs for cataract surgery topical and dropless, injection-based prophylactic medication regimens, per eye and nationally. System costs for individual topical medications and same-class dropless, injection-based medications were compared using two-sided, one-sample t-tests. RESULTS: There were 583 prophylactic topical ophthalmic purchases in MEPS. Mean system costs per eye were $76.20 ± SD 39.07 for the lowest cost topical steroid (prednisolone) compared to $4.01 for the lowest cost subconjunctival steroid (triamcinolone acetonide) (p < 0.001). Per eye, the lowest cost dropless, injection-based regimen, at $15.91, results in an $87.99 (84.7%) reduction in overall healthcare costs and a $43.64 (100%) reduction in patient out-of-pocket costs relative to the lowest cost topical regimen ($103.90 ± 43.14 mean system cost and $43.64 ± 37.32 mean out-of-pocket cost per eye). Use of intracameral moxifloxacin and subconjunctival triamcinolone acetonide can reduce annual national healthcare system and out-of-pocket costs up to $450,000,000 and $225,000,000, respectively. CONCLUSIONS: An evidence-based cataract surgery prophylactic medication regimen of intracameral moxifloxacin and subconjunctival triamcinolone acetonide can reduce healthcare system and patient out-of-pocket costs in comparison to various topical regimens.

Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

BACKGROUND AND OBJECTIVE: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR). PATIENTS AND METHODS: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients. Analysis of variance was used in subgroup analysis, receiver operating characteristic (ROC) curves were created to validate reliability of the model, and logistic regression was used to model foci and vascular abnormalities as predictors for moderate or worse disease. RESULTS: A statistically significant difference in mean number of hyporeflective foci was found between no DR and moderate non-proliferative DR (NPDR; P < 0.0001), no DR and severe NPDR (P < 0.001), no DR and proliferative DR (PDR; P < 0.0001), mild and moderate NPDR (P = 0.008), mild and severe NPDR (P < 0.001), and mild NPDR and PDR (P < 0.001). The area under the ROC curve was 0.849 (CI: 0.792 to 0.905). The threshold for detection of moderate NPDR or worse was 4.75 foci, with a sensitivity of 79.0% and a false positive rate of 20.0%. Multivariate logistic regression model incorporating hyporeflective foci with vascular abnormalities (odds ratio [OR] = 1.592, 95% CI: 1.381 to 1.835; P < 0.001) was able to accurately predict moderate disease or worse, just moderate disease (OR = 1.045, 95% CI: 1.003 to 1.089; P = 0.035), severe disease (OR = 1.050, 95% CI: 1.006 to 1.096; P = 0.027), and proliferative disease (OR = 1.050, 95% CI: 1.008 to 1.095; P = 0.018). CONCLUSIONS: NIR imaging may be an adjunct tool in screening for DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:318-325.].

Financial Health of Private Equity-Backed Groups: Perspectives From Eye Care.

BACKGROUND: In private equity (PE) buyouts of medical practices, it is common for the PE firm to raise significant levels of debt in order to finance the purchase. This debt is subsequently shouldered by the acquired practice(s). There remains a scarcity of literature quantifying the effect of PE acquisition on the subsequent financial performance of eye care practices. We aim to identify and characterize debt valuations of ophthalmology and optometry private equity-backed group (OPEG) practices, which serve as an indicator of practice financial performance. METHODS: A cross-sectional study from March 2017 to March 2022 was conducted using business development company (BDC) quarterly/annual filings to the Securities and Exchange Commission (SEC). The 2021 BDC Report was used to identify all BDCs actively filing annual reports (Form 10-Ks) and quarterly reports (Form 10-Qs) in the United States in 2021. The public filings of BDCs lending to OPEGs were searched from the inception of the OPEG's debt instrument in a BDC's portfolio and the amortized cost and fair value of each debt instrument were tabulated. A panel linear regression was used to evaluate temporal changes in OPEG valuations. RESULTS:  A total of 2,997 practice locations affiliated with 14 unique OPEGs and 17 BDCs were identified over the study period. Debt valuations of OPEGs decreased by 0.46% per quarter over the study period (95% CI: -0.88 to -0.03, P = 0.036). In the COVID-19 pre-vaccine period (March 2020 to December 2020), there was an excess (additional) 4.93% decrease in debt valuations (95% CI: -8.63 to -1.24, P = 0.010) when compared to pre-pandemic debt valuations (March 2017 to December 2019). Effects of COVID-19 on valuations stabilized during the pandemic post-vaccine period (February 2021 to March 2022), with no change in excess debt valuation compared to pre-pandemic baseline (0.60, 95% CI: -4.59 to 5.78, P = 0.822). There was an increase in practices that reported average discounted debt valuations from 20 practices (1.6%) associated with one OPEG to 1,213 practices (40.5%) associated with nine OPEGs (including 100% of newly acquired practices), despite the stabilization of COVID-19-related excess (additional) debt. CONCLUSIONS: Debt valuations of eye care practices have declined significantly post-PE investment from March 2017 to March 2022, suggesting that the financial health of these groups is volatile and vulnerable to economic contractions such as the COVID-19 pandemic. Eye care practice owners must consider long-term financial risks and impacts of subsequent patient care when selling their practice to a private equity group. Future research should assess the impact of secondary transactions of OPEGs on the financial health of practices, practitioner lifestyle, and patient outcomes.

High Variation in Inner Retinal Reflectivity Predicts Poor Visual Outcome in Patients With Central Retinal Vein Occlusion: SCORE2 Report 21.

Purpose: To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. Methods: Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. Results: Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. Conclusions: Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. Translational Relevance: Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.

Longitudinal stability of inter-eye differences in optical coherence tomography measures for identifying unilateral optic nerve lesions in multiple sclerosis.

INTRODUCTION: Optical coherence tomography (OCT)-derived peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell+inner plexiform layer (GCIPL) thickness inter-eye differences (IEDs) are robust measurements for identifying clinical history acute ON in people with MS (PwMS). This study investigated the utility and durability of these measures as longitudinal markers to identify optic nerve lesions. METHODS: Prospective, multi-center international study of PwMS (with/without clinical history of ON) and healthy controls. Data from two sites in the International MS Visual System Consortium (IMSVISUAL) were analyzed. Mixed-effects models were used to compare inter-eye differences based on MS and acute ON history. RESULTS: Average age of those with MS (n = 210) was 39.1 ± 10.8 and 190 (91%) were relapsing-remitting. Fifty-nine (28.1%) had a history of acute unilateral ON, while 9/210 (4.3%) had >1 IB episode. Median follow-up between OCT scans was 9 months. By mixed-effects modeling, IEDs were stable between first and last visits within groups for GCIPL for controls (p = 0.18), all PwMS (p = 0.74), PwMs without ON (p = 0.22), and PwMS with ON (p = 0.48). For pRNFL, IEDs were within controls (p = 0.10), all PwMS (p = 0.53), PwMS without ON history (p = 0.98), and PwMS with history of ON (p = 0.81). CONCLUSION: We demonstrated longitudinal stability of pRNFL and GCIPL IEDs as markers for optic nerve lesions in PwMS, thus reinforcing the role for OCT in demonstrating optic nerve lesions.

Follow-up Rates After Teleretinal Screening for Diabetic Retinopathy: Assessing Patient Barriers to Care.

Purpose: To study patient follow-up after they engage in a teleretinal screening program and to understand potential barriers to care. Methods: This was a retrospective analysis and a prospective study of telephone-based patient interviews of outpatients screened for diabetic retinopathy (DR) through a teleretinal referral system. Results: Of 2761 patients screened through a teleretinal referral program, 123 (4.5%) had moderate nonproliferative DR (NPDR), 83 (3.0%) had severe NPDR, and 31 (1.1%) had proliferative DR. Of the 114 patients with severe NPDR or worse, 67 (58.8%) saw an ophthalmologist within 3 months of referral. Eighty percent of interviewed patients reported they were not aware of the need for follow-up eye appointments. Conclusions: Of patients with severe retinopathy or worse, 58.8% presented for in-person evaluation and treatment within 3 months of screening. Although this result was negatively affected by factors related to the COVID-19 pandemic, key elements of patient education and improved referral strategies to facilitate in-person treatment are essential to improving follow-up after patients engage in telescreening.

Private equity in ophthalmology and optometry: a time series analysis from 2012 to 2021.

Purpose: To identify temporal and geographic trends in private equity (PE)-backed acquisitions of ophthalmology and optometry practices in the United States from 2012 to 2021. Methods: In this cross-sectional time series, acquisition data from 10/21/2019 to 9/1/2021 and previously published data from 1/1/2012 to 10/20/2019 were analyzed. Acquisition data were compiled from 6 financial databases, 5 industry news outlets, and publicly available press releases. Linear regression models were used to compare rates of acquisition. Outcomes included number of total acquisitions, practice type, locations, provider details, and geographic footprint. Results: A total of 245 practices associated with 614 clinical locations and 948 ophthalmologists or optometrists were acquired by 30 PE-backed platform companies between 10/21/2019 and 9/1/2021. Of 30 platform companies, 18 were new vis-à-vis our prior study. Of these acquisitions, 127 were comprehensive practices, 29 were retina practices, and 89 were optometry practices. From 2012 to 2021, monthly acquisitions increased by 0.947 acquisitions per year (P < 0.001*). Texas, Florida, Michigan, and New Jersey were the states with the greatest number of PE acquisitions, with 55, 48, 29, and 28 clinic acquisitions, respectively. Average monthly PE acquisitions were 5.71 per month from 1/1/2019 to 2/29/2020 (pre-COVID), 5.30 per month from 3/1/2020 to 12/31/2020 (COVID pre-vaccine [P = 0.81]), and 8.78 per month from 1/1/2021 to 9/1/2021 (COVID post-vaccine [P = 0.20]). Conclusions: PE acquisitions increased during the period 2012-2021 as companies continue to utilize regionally focused strategies for acquisitions.

Paralysis Versus Non-Paralysis Anesthesia for Operative Laryngoscopy: A Randomized Controlled Trial.

OBJECTIVE: To compare outcomes between two standard-of-care anesthesia regimens for operative laryngoscopy: general anesthesia with a neuromuscular blocking agent (NMBA) versus remifentanil and propofol (non-NMBA). METHODS: This was a prospective, single-blinded, randomized controlled trial at a tertiary care center. Patients were randomized to either anesthesia using rocuronium (NMBA) or with remifentanil/propofol infusion alone (non-NMBA). Intraoperative impressions, anesthesia data, and post-operative patient surveys were collected. RESULTS: Sixty-one patients who underwent suspension laryngoscopy from 2020 to 2022 were included (25 female, 36 male, ranging 20-81 years). Thirty patients were enrolled in the NMBA arm and 31 patients in the non-NMBA arm. Heart rate and mean arterial pressure were higher in the NMBA (p < 0.01). Patients in the non-NMBA group were more likely to require vasopressors (p = 0.04, RR = 3.08 [0.86-11.05]). Surgeons were more frequently satisfied with conditions in the NMBA group (86.7%) compared to the non-NMBA group (58.1%, p < 0.01). Procedures were more likely to be paused due to movement in the non-NMBA group (45.1%) compared to the NMBA group (16.6%, p < 0.03, RR = 2.26 [1.02-4.99]). Patients in the non-NMBA group were more likely to endorse myalgia the week after surgery (44%) compared to the NMBA group (8.3%, p < 0.01) and reported higher average pain levels on a 0-10 pain scale (3.7) compared to the paralysis group (2.0). CONCLUSIONS: Anesthesia with rocuronium was associated with better intraoperative conditions and postoperative pain compared to anesthesia with remifentanil/propofol. Remifentanil/propofol were associated with lower blood pressure and suppression of laryngoscopy-associated tachycardia. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:2654-2664, 2023.

Where's the Vision? The Importance of Visual Outcomes in Neurologic Disorders: The 2021 H. Houston Merritt Lecture.

Neurologists have long recognized the importance of the visual system in the diagnosis and monitoring of neurologic disorders. This is particularly true because approximately 50% of the brain's pathways subserve afferent and efferent aspects of vision. During the past 30 years, researchers and clinicians have further refined this concept to include investigation of the visual system for patients with specific neurologic diagnoses, including multiple sclerosis (MS), concussion, Parkinson disease (PD), and conditions along the spectrum of Alzheimer disease (AD, mild cognitive impairment, and subjective cognitive decline). This review highlights the visual "toolbox" that has been developed over the past 3 decades and beyond to capture both structural and functional aspects of vision in neurologic disease. Although the efforts to accelerate the emphasis on structure-function relationships in neurologic disorders began with MS during the early 2000s, such investigations have broadened to recognize the need for outcomes of visual pathway structure, function, and quality of life for clinical trials of therapies across the spectrum of neurologic disorders. This review begins with a patient case study highlighting the importance using the most modern technologies for visual pathway assessment, including optical coherence tomography. We emphasize that both structural and functional tools for vision testing can be used in parallel to detect what might otherwise be subclinical events or markers of visual and, perhaps, more global neurologic decline. Such measures will be critical because clinical trials and therapies become more available across the neurologic disease spectrum.

MALT Lymphoma Presenting with Peripheral Ulcerative Keratitis.

Objective: To report a case of ocular mucosa-associated lymphoid tissue (MALT) lymphoma presenting with peripheral ulcerative keratitis. Methods: A 58-year-old man with a history of vitreous syneresis in both eyes and glaucoma presented with an abnormal, painful sensation of the left eye and mild hyperemia. Physical examination revealed peripheral ulcerative keratitis superiorly and a salmon-colored lesion in the superior conjunctiva. Results: The differential diagnosis of superior corneal thinning includes collagen vascular disease, Terrien's marginal degeneration, infectious keratitis, and other forms of peripheral keratitis. Our patient was diagnosed with conjunctival MALT lymphoma by surgical excision of the mass, and the peripheral ulcerative keratitis may be related to this diagnosis. Conclusion: Although rare, this case demonstrates a peripheral keratitis possibly related to the underlying disease of MALT lymphoma. The patient is being treated with local radiation treatment.

The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration.

PURPOSE: Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD. DESIGN: Retrospective cohort study. PARTICIPANTS: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. METHODS: Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions. MAIN OUTCOME MEASURES: Anti-VEGF agent selection for the first four injections and at one year were examined. RESULTS: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p < .001), third (3.1% vs. 41.3%, p < .001), fourth injections (4.7% vs. 40.4%, p < .001), and at 1 year (0% vs. 33.8%, p < .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p < .001), third (76.3% vs. 41.5%, p < .001), and fourth injections (76.7% vs. 43.4%, p < .001), and at 1 year (77.0% vs. 52.7%, p < .001). CONCLUSIONS: Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.

Documentation of recovery from vitamin A deficiency-related retinopathy via multimodal imaging and electroretinogram testing.

PURPOSE: To describe vitamin A deficiency using multimodal functional visual assessments and imaging. METHODS/CASE: A 50-year-old female with past medical history significant for Roux-en-Y gastric bypass surgery complained of nyctalopia and "yellowing" of vision. RESULTS: Vitamin A levels were noted to be < 0.06 mg/L (normal 0.3-0.12 mg/L). Fundus examination was notable for peripheral yellow punctate lesions, superior arcuate defects on HVF 30-2 testing, an indistinct ellipsoid zone on SD-OCT, and absent rod responses and severely reduced amplitudes for the cone photoreceptors on full-field ERG. These findings resolved with initiation of parenteral vitamin A supplementation. CONCLUSION: This report documents an example of vitamin A deficiency in the developed world. We aim to provide a comprehensive description of clinical examination and multimodal imaging findings before and after vitamin supplementation for vitamin A deficiency.

Apparent lack of association of COVID-19 vaccination with Herpes Zoster.

Purpose: Herpes zoster (HZ) has been identified as a potential association with the BNT162b2 COVID-19 vaccination. This study evaluated this possible association in a cohort of patients receiving the vaccination. Methods: Epic electronic health records of adult patients who received at least one COVID-19 vaccination between January 12, 2020 and 9/30/2021 within the NYU Langone Health were reviewed to analyze a new diagnosis of herpes zoster within 3 months before compared to 3 months after vaccination. Results: Of the 596,111 patients who received at least one COVID-19 vaccination, 716 patients were diagnosed with HZ within three months prior to vaccination, compared to 781 patients diagnosed within 3 months afterwards. Using the chi-square test for independence of proportions, there was not a statistically significant difference in frequency of HZ before (proportion: 0.0012, 95% CI: [0.0011, 0.0013]) vs. after vaccination (proportion: 0.0013, 95% CI: [0.0012, 0.0014]); (p = 0.093). Conclusions and importance: This study did not find evidence of an association between COVID-19 vaccination and a new diagnosis of HZ. We encourage health care professionals to strongly recommend COVID-19 vaccinations per Centers for Disease Control (CDC) recommendations and vaccination against HZ according to Food and Drug Administration (FDA) approval for the recombinant zoster vaccine.

Utilization of Crowdfunding for Cataract and LASIK Procedures.

PURPOSE: To study the nature of crowdfunding campaigns for common ophthalmologic procedures. METHODS: Cross sectional, retrospective study of campaigns on GoFundMe.com from January 1st, 2021 to July 31st, 2021. All domestic and international campaigns referring to cataract and intraocular lens placement or LASIK procedures, excluding those with non-ophthalmologic conditions or campaigns for multiple conditions. Descriptive analysis of campaigns including condition, country of origin of patient, total and median value raised, total and median value sought, age of the patient, funding goal met, insurance status when possible. Total and median funds raised and sought, international versus domestic campaigns, success rate for campaigns, percent of campaigns involving children, percent of campaigns mentioning insurance. RESULTS: 137 campaigns were identified, 67.9% (93/137) were for cataract and 32.1% (44/137) were for LASIK. 13.1% (18/137) of campaigns were international. 7.3% (10/137) campaigns were successful at reaching fing goals. Of successful campaigns, 70.0% (7/10) were for cataract and 30.0% (3/10) were for LASIK. Total value raised (in USD) was $131,763, where $106,593 was for cataract and $25,170 was for LASIK. The median value sought overall was $5,000, where the median sought for cataract procedures was $5,000 and the median for LASIK was $4,000. The median value raised was $395. 5.8% (8/137) of campaigns mentioned minors. 12.5% (1/8) of campaigns for children or minors successfully met funding goals compared to 7.0% (9/129) adult campaigns. The total funds raised for children or minors was $9,224 with a goal of $41,050. The total funds raised for adults was $122,539 out of a goal of $775,617. 14.6% (20/137) campaigns mentioned insurance coverage, of which 85% (17/20) were for cataract and 15.0% (3/20) were for LASIK. Premium lenses (toric, multifocal, etc.) were mentioned in 1.1% of cataract campaigns (1/93) as being cost prohibitive. CONCLUSIONS: Crowdfunding is ineffective as a means for patients to raise funds for ophthalmic procedures. The broad range of financial requests within campaigns indicates a large patient knowledge gap in cost for procedures.

Predictive Performance of the International Takotsubo Registry Score in the Diagnosis of Takotsubo Syndrome Among Women with Non-ST Segment Elevation Myocardial Infarction.

Background: The International Takotsubo Registry (InterTAK) score was developed to assess the probability of takotsubo syndrome (TTS) and to distinguish it from acute coronary syndrome, which has a similar clinical presentation. A European Society of Cardiology (ESC) consensus statement suggests invasive coronary angiography may be deferred in patients with non-ST segment elevation myocardial infarction (NSTEMI) and high probability of TTS. We aimed to determine the predictive performance of the InterTAK score in a real-world population of NSTEMIs. Materials and Methods: The InterTAK score was retrospectively calculated for consecutive female patients with NSTEMI who underwent invasive coronary angiography at two academic medical centers in New York City from March 2016 to August 2018. Results: Among 375 women with NSTEMI, 15 (4%) had InterTAK score >70, indicating high probability of TTS. Ten (67%) met ESC TTS criteria for a noninvasive strategy, among whom seven had TTS, two had spontaneous coronary artery dissection (SCAD), and one had coronary artery disease requiring revascularization. A total of 48 women (13% of cohort) had a final diagnosis of TTS. The InterTAK score had an area under the receiver operating characteristics curve (AUC) of 0.82 (95% confidence interval, 0.75-0.88) for TTS, with 21% sensitivity and 98% specificity at score >70. Conclusions: In this real-world sample of consecutive female NSTEMI patients, the InterTAK score was predictive of TTS but a high score was rare, and use of the score to obviate invasive angiography could have resulted in delay of revascularization and missed diagnosis of SCAD for a small number of patients. The InterTAK score should be used in conjunction with other clinical variables for angiographic referral.

Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry.

BACKGROUND: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. METHODS: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression. RESULTS: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1-2), and median VFS was 1 (IQR 0-2). Median follow-up time was 5.2 years (IQR 2.4-9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression. CONCLUSIONS: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS.

Early ICD lead failure in defibrillator systems with multiple leads via cephalic access.

INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are proven to prevent sudden death in patients at elevated risk for sustained ventricular tachycardia or fibrillation. Complications related to ICD failure can stem from lead dysfunction, manufacturing defects, patient characteristics, or implantation technique. We conducted a review of all ICD leads implanted at our center from 2011 to 2017 to determine risk factors for premature lead failure. METHODS: We conducted a retrospective review of patients of all ICD leads implanted from December 2011 to June 2017 at our institution. A total of 660 patients (Biotronik Linox S/SD, n = 281; Sprint Quatro, n = 207; Durata, n = 121; Endotak, n = 51) underwent ICD implantations. Patient and lead characteristics, procedural outcomes and complications were recorded. Lead failure was defined per Heart Rhythm Society lead-management consensus as a lack of procedural or clinical success, thus requiring an extraction of the lead. Patient and lead outcomes were recorded and variables associated with lead failure were assessed by the Kaplan-Meier method. RESULTS: Overall failure rate was similar for all leads: Linox S/SD-0.29%/year; Sprint Quattro-0.21%/year, Durata-0.39%/year and Endotak Reliance-0.0% (P = .769). No difference was found in overall survival when comparing all ICD manufacturers during the study period. Subgroup analysis revealed the risk of premature lead failure was particularly pronounced in multi-lead ICD systems implanted via cephalic access (P < .001). The estimated failure rate of Linox leads implanted via cephalic access in multi-lead systems was 19%/year. The estimated failure rate of non-Linox leads implanted via cephalic access in multi-lead systems was 11%/year. Neither age, nor gender were risk factors for lead failure in the Linox, or non-Linox cohorts. CONCLUSION: All analyzed ICD leads were found to have a similar overall risk of premature failure. ICD lead implantation via cephalic access in multilead ICD systems may be a previously unidentified risk factor for premature ICD lead failure, although these findings require further validation.

RAGE binds preamyloid IAPP intermediates and mediates pancreatic ß cell proteotoxicity.

Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in ß cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) ß cell and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion protected pancreatic islets, ß cells, and smooth muscle cells from h-IAPP-induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were protected from amyloid deposition, loss of ß cell area, ß cell inflammation, stress, apoptosis, and glucose intolerance. These findings establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting the IAPP/RAGE axis is a potential strategy to mitigate this source of ß cell dysfunction in metabolic disease.