The degree of retinopathy is equally predictive for renal and macrovascular outcomes in the ACCORD Trial

AIMS: Diabetic retinopathy (DR) is associated with a higher risk of renal and cardiovascular events. We sought to compare the risk for renal versus cardiovascular (CV) outcomes, stratified by retinopathy severity. METHODS: ACCORD was a randomized trial of people with type 2 diabetes, at high-risk for CV disease. A subgroup (n=3,369 from 71 clinics) had stereoscopic fundus photographs graded centrally. Participants were stratified at baseline to moderate/severe DR or no/mild DR and were monitored for renal and CV outcomes at follow-up visits over 4 years. The composite renal outcome was composed of serum creatinine doubling, macroalbuminuria, or end-stage renal disease. The composite CV outcome was the ACCORD trial primary outcome. Competing risk techniques were used to estimate the relative risk (RR) of renal versus CV composite outcomes within each DR stratum. RESULTS: The hazards ratio for doubling of serum creatinine and incident CV event in the moderate/severe DR versus no/mild DR strata were: 2.31 (95% CI: 1.25-4.26) and 1.98 (95% CI: 1.49-2.62), respectively. The RR of the two composite outcomes was highly similar in the no/mild DR stratum (adjusted RR at 4 years for CV versus renal events=0.96, 95% CI: 0.72-1.28) and the moderate/severe DR stratum (adjusted RR=0.92, 95% CI: 0.64-1.31). CONCLUSIONS: Thus, in people with type 2 diabetes at high risk for cardiovascular disease, incident CV versus renal events was similar, irrespective of the severity of the DR. Further evaluation of the specificity of DR for microvascular versus macrovascular events in other populations is warranted

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Green or Yellow Laser Treatment for Diabetic Macular Edema

Purpose: Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomic endpoints in eyes with diabetic macular edema. Methods: Data from two randomized clinical trials were evaluated for differences in visual acuity (VA) and optical coherence tomography (OCT) parameters, eyes were assigned to sham injection+prompt laser, ranibizumab+prompt laser, or prompt laser only; among subgroups of eyes treated exclusively and electively with either green or yellow laser. Results: In the sham injection+prompt laser group, the mean VA letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4±14 and +5.1±13 at the 52-week visit (P = 0.06), and +2.4±15 and +6.0±13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in OCT thickness. When comparing wavelength groups in the ranibizumab+prompt laser and prompt-laser only groups, meaningful differences in VA and OCT thickness were not detected at 1 or 2 years. Conclusion: A trend towards improved vision outcome with yellow laser observed in one trial was not corroborated by anatomic outcomes or by the other trial. Without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other

Intravitreal moxifloxacin in the management of Ochrobactrum intermedium endophthalmitis due to metallic intraocular foreign body

A healthy 34-year-old man presented with Ochrobactrum intermedium endophthalmitis due to a metallic intraocular foreign body. After vitrectomy, lensectomy, removal of the metallic intraocular foreign body, intravitreal vancomycin and ceftazidime, and systemic ciprofloxacin, intraocular inflammation worsened. Repeat vitreous culture confirmed persistent endophthalmitis due to multidrug-resistant O. intermedium . The endophthalmitis successfully resolved after the administration of intravitreal moxifloxacin

Application of Random Forests Methods to Diabetic Retinopathy Classification Analyses

<div><p>Background</p><p>Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States and world-wide. DR is a silent disease that may go unnoticed until it is too late for effective treatment. Therefore, early detection could improve the chances of therapeutic interventions that would alleviate its effects.</p><p>Methodology</p><p>Graded fundus photography and systemic data from 3443 ACCORD-Eye Study participants were used to estimate Random Forest (RF) and logistic regression classifiers. We studied the impact of sample size on classifier performance and the possibility of using RF generated class conditional probabilities as metrics describing DR risk. RF measures of variable importance are used to detect factors that affect classification performance.</p><p>Principal Findings</p><p>Both types of data were informative when discriminating participants with or without DR. RF based models produced much higher classification accuracy than those based on logistic regression. Combining both types of data did not increase accuracy but did increase statistical discrimination of healthy participants who subsequently did or did not have DR events during four years of follow-up. RF variable importance criteria revealed that microaneurysms counts in both eyes seemed to play the most important role in discrimination among the graded fundus variables, while the number of medicines and diabetes duration were the most relevant among the systemic variables.</p><p>Conclusions and Significance</p><p>We have introduced RF methods to DR classification analyses based on fundus photography data. In addition, we propose an approach to DR risk assessment based on metrics derived from graded fundus photography and systemic data. Our results suggest that RF methods could be a valuable tool to diagnose DR diagnosis and evaluate its progression.</p></div

Performance across sample sizes of both RF (right panel) and LR is shown for three different scenarios: 1) Only eye data; 2) all variables in the study; and 3) only systemic data.

<p>The addition of systemic variables did not lead to significant increases in classification accuracy.</p

RF and LR performance using all available eye variables and a subset of eye variables selected by an expert as more clinically relevant.

<p>While this selection led to some improvements for LR it had very little impact on RF performance.</p

The RF probabilities of having DR were estimated for two groups of participants who were not diagnosed as DR at baseline: a) those who had a DR event (> = 3 step ETDRS progression, vitrectomy, or laser photocoagulation) during follow-up and 2) those who did not.

<p>*Wilcoxon rank sum test, std – standard deviation.</p><p>Estimation was made using baseline data.</p