Incidence of ocular pathology following bariatric surgery for with morbid obesity across a large United States National Database.

BACKGROUND/OBJECTIVES: Bariatric surgery, as indicated for treatment of morbid obesity, has been studied in association with short term effects on ocular pathology. However, effects of surgery on postoperative disease incidence is largely unknown. SUBJECTS/METHODS: In this retrospective cohort study, the TriNetX United States Collaborative Network national database, was queried for patients with an ICD-10 code for morbid obesity and a procedural code for bariatric surgery. Patients were propensity score matched across baseline demographics at the time of surgery and compared to those presenting with an ICD10 code for morbid obesity with no records of a procedural code for bariatric surgery, identifying 42,408 patients per cohort. New diagnoses or procedural codes found after the surgical index date for diabetic retinopathy, age-related macular degeneration, glaucoma, low vision, and blindness along with pertinent treatment metrics were monitored. RESULTS: Bariatric surgery was found to be associated with reduced future risk of diabetic retinopathy (RR: 0.283; 95% CI: 0.252-0.319), macular edema (RR: 0.224; 95% CI: 0.170-0.297), vitreous hemorrhage (RR: 0.459; 95% CI: 0.323-0.653), ocular hypertension (RR: 0.387; 95% CI: 0.387-0.487), glaucoma (RR: 0.360; 95% CI: 0.326-0.399), use of ocular pressure lowering medications (RR: 0.565; 95% CI: 0.496-0.644), age-related macular degeneration (RR: 0.628; 95% CI: 0.447-0.882), cataract surgery (RR: 0.524; 95% CI: 0.448-0.612), and low vision and blindness (RR: 0.328; 95% CI: 0.294-0.365) compared to patients not surgically managed. CONCLUSIONS: The present analysis comprising a large US cohort of patients suggests that bariatric surgery is associated with a decreased risk of future ocular morbidity and mortality.

Associations between lipid abnormalities and diabetic retinopathy across a large United States national database.

BACKGROUND/OBJECTIVES: While dyslipidaemia has been suggested as a potential risk factor for diabetic retinopathy (DR), previous studies have reported conflicting findings. This study aimed to better characterize the relationship between abnormal serum levels of various lipid markers and the risk of the development and progression of DR. SUBJECTS/METHODS: This retrospective cohort study utilized a United States national database of electronic medical records. Adults with a history of type 2 diabetes mellitus without type 1 diabetes mellitus were divided into cohorts based on the presence of abnormal serum levels of various lipid markers. Propensity score matching was performed to match cohorts with abnormal lipid levels to those with normal lipid levels on covariates. The cohorts were then compared to evaluate the hazard ratios (HR) of receiving a new DR diagnosis, pars plana vitrectomy, panretinal photocoagulation, vitreous haemorrhage, proliferative diabetic retinopathy, diabetic macular oedema (DMO), and traction retinal detachment. RESULTS: The database contained 1,126,231 eligible patients (mean age: 60.8 [14.2] years; 46.0% female). Among patients without prior DR, low HDL (HR = 0.94, CI = 0.90-0.98), total cholesterol (HR = 0.88, CI = 0.85-0.91), and high triglyceride (HR = 0.91, CI = 0.86-0.97) levels were associated with a decreased risk of receiving a DR diagnosis. Among patients with preexisting DR, high LDL levels was associated with an increased risk of DMO (HR = 1.42, CI = 1.15-1.75), whereas low HDL levels was associated with a marginally decreased risk (HR = 0.92, CI = 0.85-0.99). CONCLUSIONS: Elevated levels of markers of dyslipidaemia are inversely associated with the risk of receiving a DR diagnosis, but this relationship is blunted after the onset of DR.

Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Long-Term Visual Outcomes in Patients With Idiopathic Epiretinal Membrane Surgery.

BACKGROUND AND OBJECTIVE: Our aim was to assess long-term outcomes following surgical repair of idiopathic epiretinal membrane (ERM) with pars plana vitrectomy (PPV) and membrane peel (MP). PATIENTS AND METHODS: A retrospective study evaluated patients with idiopathic ERM who underwent surgical repair at a single academic tertiary center with five to nine years of postoperative follow-up, assessing preoperative characteristics, surgical techniques, best visual acuity (BVA), and optical coherence tomography biomarkers at various time points. RESULTS: The study involved 67 patients (72 eyes) with an average postoperative follow-up of 82.8 ± 18.8 months. Patients with cone outer segment tips integrity at initial presentation and 1-year follow-up and patients with external limiting membrane and ellipsoid zone integrity at 1-year follow-up were noted to have significantly better long-term visual acuity than those without. More than 85% of patients achieved a BVA > 70 seven years after surgical repair. CONCLUSIONS: Vitreoretinal surgery for idiopathic ERM resulted in improved anatomical recovery and sustained visual acuity gain over long-term follow-up. [Ophthalmic Surg Lasers Imaging Retina 2024;55:70-77.].

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort.

BACKGROUND AND OBJECTIVE: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. PATIENTS AND METHODS: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. RESULTS: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. CONCLUSION: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [Ophthalmic Surg Lasers Imaging Retina 2023;54:626-633.].

Effect of Prefilled vs Vial-Drawn Syringes on Sustained Increases in Intraocular Pressure in Patients Treated With Aflibercept.

Purpose: To evaluate the effect of syringe type on developing sustained intraocular pressure (IOP) increases. Methods: This retrospective cohort study included patients in a single academic center receiving antivascular endothelial growth factor (anti-VEGF) injections from 2012 to 2022 for various indications. Patients were grouped by anti-VEGF treatment of either vial-drawn or prefilled syringe delivery. Trends in IOP were recorded for 1 year after treatment began. Development of sustained IOP increase, ocular hypertension, and glaucoma was recorded. Sustained IOP increase was defined as ≥5 mm Hg above baseline for at least 4 weeks. Results: Of 257 total patients, 6 (2.3%) developed sustained IOP increases throughout the study's duration. No significant differences were noted with respect to prefilled versus vial-drawn syringe status on the development of sustained IOP increases or incident glaucoma (IOP: 1.8% vs 2.7%, respectively, P = .65; glaucoma: 0.0% vs 2.0%, respectively, P = .14). Patients treated with prefilled syringes were significantly less likely to develop ocular hypertension (2.8% vs 8.8%, P < .05). Conclusions: This study found that aflibercept intravitreal injection with prefilled syringes was not associated with a significant increase in IOP-related adverse effects when compared with those treated with vial-drawn syringes.

Lack of association between Lp(a) and retinal vein occlusion in a single institution and US national database.

OBJECTIVE: This study examines associations between lipoprotein(a) (Lp[a]), a low-density-like lipoprotein, and renal vein occlusion (RVO) in US cohorts to characterize its prognostic role in the setting of RVO. DESIGN: A two-phase retrospective cohort study. METHODS: In the first phase, patients with RVO and a Lp(a) quantitative laboratory value at a single tertiary centre were reviewed. Lp(a) status was assessed in association with age of RVO diagnosis, visual acuity, time to development of RVO, and central subfield thickness. In the second phase, the TriNetX US Collaborative Network, a large national database, also was queried for the presence of high or low Lp(a) values and diagnoses of RVO. RESULTS: The single tertiary care centre identified 45 patients with RVO and a laboratory value of Lp(a), finding no significant associations with respect to Lp(a) status and age of RVO onset, time from the laboratory draw to the development of RVO, visual acuity, and central subfield thickness (p > 0.05 for all). The TriNetX national database identified 35,687 patients with a high Lp(a) value (>30 mg/dL or 61 nmol/L) and 51,692 with a low Lp(a) value. An elevated Lp(a) value was not associated with higher odds of central (odds ratio [OR] = 1.15; 95% CI, 0.88-1.50) or branch RVO (OR = 1.01; 95% CI, 0.76-1.36). CONCLUSION: Taken together, this analysis suggests a lack of association between Lp(a) value and risk of RVO. This study highlights the benefit of large national databases in the validation of laboratory value predictors identified through small-cohort observational studies.

Clinical trials targeting the gut-microbiome to effect ocular health: a systematic review.

Clinical trials targeting the gut microbiome to mitigate ocular disease are now on the horizon. A review of clinical data thus far is essential to determine future directions in this novel promising field. This review examines recent clinical trials that support the plausibility of a gut-eye axis, and may form the basis of novel clinical interventions. PubMed was queried for English language clinical studies examining the relationships between gut microbiota and ocular pathology. 25 studies were extracted from 828 candidate publications, which suggest that gut imbalance is associated with ocular pathology. Of these, only four interventional studies exist which suggest probiotic supplementation or fecal microbiota transplant can reduce symptoms of chalazion or uveitis. The gut-eye axis appears to hold clinical relevance, but current data is limited in sample size and design. Further investigation via longitudinal clinical trials may be warranted.

Time to fellow eye involvement in patients with unilateral diabetic macular oedema.

OBJECTIVE: To examine the time to onset of disease in the fellow eye of patients with unilateral DMO in routine clinical practice and to identify risk factors for development of bilateral DMO. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred forty treatment-naive patients 18 years or older with unilateral DMO presenting to Cole Eye Institute between January 2012 and July 2021. METHODS: Records of patients with unilateral DMO were reviewed for development of DMO in the fellow eye. Demographic, diabetic, ocular, and systemic characteristics were collected at initial DMO diagnosis date. Bivariate and multivariate analyses were performed and significant factors were modelled using Kaplan-Meier curves. RESULTS: Fifty patients with conversion to bilateral DMO and 90 patients without conversion were identified. Average time to bilateral DMO was 15.0 ± 15.7 months. 64% of patients converted within 1 year and 90% converted within 3 years. HbA1c (p = 0.003), diabetic retinopathy duration (p = 0.029), and diabetic foot disease (DFD) (p = 0.002) were identified as significant risk factors for conversion. Patients with better visual acuity at time of initial diagnosis and history of panretinal photocoagulation (PRP) (p = 0.044) or focal laser (p = 0.035) in the primary eye were also more likely to convert. CONCLUSIONS: Participants were most likely to develop fellow eye DMO within the first year after initial DMO diagnosis. In routine clinical practice, poor glycaemic control and DFD were risk factors associated with bilateral eye involvement. Clinicians may consider screening the fellow eye of high-risk individuals at each appointment within the first year of diagnosis.

Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence.

PURPOSE: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. METHODS: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. RESULTS: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity (P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity (P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity (P = 0.018 and 0.024, respectively). CONCLUSIONS: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [Ophthalmic Surg Lasers Imaging Retina 2023;54:24-31.].

Visual, Anatomic Outcomes, and Natural History of Retinal Nerve Fiber Layer Schisis in Patients Undergoing Epiretinal Membrane Surgery.

PURPOSE: To evaluate the anatomic and visual outcomes of patients with idiopathic epiretinal membranes (ERMs) complicated by schisis of the retinal nerve fiber layer (sRNFL) in routine clinical practice. DESIGN: Retrospective case-control study. PARTICIPANTS: Patients undergoing idiopathic ERM surgery at Cole Eye Institute from 2013 to 2021. METHODS: Patients were grouped by the presence or absence of sRNFL before surgery. Preoperative and postoperative data were collected regarding visual acuity (VA), changes in central subfield thickness (CST) over time, and presence of cystoid macular edema. MAIN OUTCOME MEASURES: Frequency of sRNFL in patients undergoing idiopathic ERM surgery. RESULTS: Overall, 48 (53.9%) of 89 patients presented with sRNFL. Schisis of the retinal nerve fiber layer patients presented with significantly decreased VA compared with those without (58.63 ± 12.48 vs. 67.68 ± 7.84 ETDRS letters, P < 0.001, respectively). At the final follow-up after ERM removal, there was no significant difference in final VA in patients with sRNFL compared with those without (71.16 ± 2.93 vs. 74.11 ± 2.76, P = 0.467). At presentation, patients with sRNFL had greater CST than those without (454 ± 10.01 vs. 436 ± 0.23, P = 0.23). This difference persisted at the 90-day follow-up after ERM removal (402 ± 8.08 vs. 375 ± 10.19 µm, P = 0.043). The resolution of sRNFL was reported at postoperative week 1 in 30 (96.7%) of 31 cases. CONCLUSIONS: Schisis of the retinal nerve fiber layer is a microstructural feature in > 50% of idiopathic ERMs in routine clinical practice and carries visual significance on presentation and anatomic significance postoperatively. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Interventions to reduce loss to follow up in common retinal pathology: A systematic review.

PURPOSE: Loss to follow-up or fragmented follow-up episodes (LTFU) may contribute to suboptimal clinical outcomes, especially when comparing real world data to clinical trials. This systemic review gathers available evidence around interventions meant to decrease the LTFU in AMD, RVO, and DME patients. PATIENTS AND METHODS: PubMed was queried using a literature search strategy and reviewed by the authors. Studies with interventions aimed at reducing lost to follow up were included. RESULTS: Ten studies were extracted from 89 candidate publications. DISCUSSION: Telephone interventions featuring assistance in scheduling in improving LTFU in urban, African American populations over 50 years old with diabetic retinopathy. The same interventions have shown promise in glaucoma, but remain understudied in AMD, RVO, and other geographic, ethnic, and socioeconomic demographics. CONCLUSION: No sole intervention with efficacy in improving LTFU has been developed. A standardized definition of LTFU, as well as testing interventions across broad age, geography, ethnic, racial, and socioeconomic lines. Longitudinal data would also add credence to the efficacy of purported interventions. OTHER: No sources of funding for this article.

The Impact of Travel Distance on Rhegmatogenous Retinal Detachment Presentation and Outcomes.

BACKGROUND AND OBJECTIVE: Rhegmatogenous retinal detachment (RRD) requires urgent surgical intervention. The effect of travel distance on RRD outcomes is unclear. PATIENTS AND METHODS: This retrospective cohort study included 642 patients who underwent RRD repair at Cole Eye Institute from 2012 to 2020. Google Maps was used to calculate the travel distance in miles from the residential zip code to the presenting and surgery location addresses. Multivariable logistic and bivariate linear regressions were used to compare macula-off status and best-corrected visual acuity (BCVA) in ETDRS letters at presentation and at 6-month follow-up, with patient travel distance divided into < 25 miles, 25 to 50 miles, and > 50 miles. RESULTS: Four hundred sixty-two patients were examined in the final cohort. The retinal reattachment rate was 94.3% for less than 25 miles, 96.3% for 25 to 50 miles, and 95.9% for greater than 50 miles (P = 0.63). In multivariable analysis, distance to presenting location was not associated with macula-off status (P = 0.69) or BCVA at follow-up (P = 0.27). Oneway analysis of distance and time from presentation to surgery in days revealed that distance to surgical site was associated with longer time to surgery (P = 0.003). Subset analysis of patients with income less than $25,520 (n = 18) revealed greater distance to presenting and surgical location was associated with longer time to surgery (P < .0001), but was not associated with BCVA at follow-up (P = 0.53). CONCLUSIONS: This data suggests that patients who live further from the hospital achieve equivalent outcomes from RRD repair, despite delays in surgery. [Ophthalmic Surg Lasers Imaging Retina 2022;53:666-672.].

Functional imaging of mitochondria in genetically confirmed retinal dystrophies using flavoprotein fluorescence.

BACKGROUND: Whether by indirect oxidative stress or direct genetic defect, various genetic retinal dystrophies involve mitochondrial stress. Mitochondrial flavoprotein fluorescence (FPF), reported as either average signal intensity or variability (heterogeneity), may serve as a direct, quantifiable marker of oxidative stress. MATERIALS AND METHODS: This observational study enrolled patients with genetically confirmed retinal dystrophies between January and December 2021. Patients with concomitant maculopathy and ocular hypertension were excluded. Patients were FPF imaged with OcuMet Beacon® third generation device during routine outpatient visit. RESULTS: The final analysis cohort included 242 images from 157 patients. Mean FPF intensity was significantly increased between age matched controls and patients with confirmed rod-cone dystrophy, Stargardt disease, Bardet-Biedl syndrome (BBS), and Mitochondrial ATP synthase mutation (P ≤ 0.007). Mean FPF heterogeneity was significantly increased between age matched controls and patients with confirmed rod-cone dystrophy, Stargardt disease, and BBS (P ≤ 0.011). FPF lesions were noted to correlate with Fundus Autofluorescence (FAF) lesions in diseases examined. CONCLUSIONS: FPF intensity and heterogeneity significantly increased in patients with retinal dystrophies. The correlation of FPF lesions with FAF lesions implies FPF may be a clinically useful biomarker in patients with IRDs.

This study found increases in flavoprotein fluorescence signal in patients with genetically confirmed inherited retinal dystrophies compared to age matched controls. Flavoprotein fluorescence signal correlated with fundus autofluorescence findings, suggesting clinical utility of novel signal.

Progression to Vision-Threatening Retinopathy Complications Following Panretinal Laser for Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To report the time in which patients with panretinal photocoagulation (PDR) progress to vision-threatening retinopathy (VTR) complications after receiving PRP, and risk factors in routine clinical practice. PATIENTS AND METHODS: Records of patients with complete PRP for PDR were retrospectively reviewed for up to 3.5 years after PRP. Two hundred twenty eyes were selected. RESULTS: Time from PRP to VTR was 1.25 ± 0.82 years. Age, Black race, neovascularization of the disc on examination, diabetic foot disease (DFD), and high-risk PDR characteristics on fluorescein angiography were identified as significant risk factors. Half of patients with DFD on examination developed a VTR within 1.5 years after PRP (P < .001). CONCLUSION: In clinical practice, providers may consider DFD and Black race as predictors of time to VTR event within 4 years after PRP in patients with PDR. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):186-193.].

Photobiomodulation Therapy for Age-Related Macular Degeneration and Diabetic Retinopathy: A Review.

PURPOSE: Photobiomodulation therapy (PBT) has emerged as a possible treatment for age-related macular degeneration (AMD) and diabetic retinopathy (DR). This review seeks to summarize the application of PBT in AMD and DR. METHODS: The National Clinical Trial (NCT) database and PubMed were queried using a literature search strategy and reviewed by the authors. RESULTS: Fourteen studies examining the application of PBT for AMD and nine studies examining the application of PBT for diabetic macular edema (DME) were extracted from 60 candidate publications. DISCUSSION: Despite notable methodological differences between studies, PBT has been reported to treat certain DR and AMD patients. DR patients with center involving DME and VA ≥ 20/25 have demonstrated response to treatment. AMD patients at Age-Related Eye Disease Study Stages 2-4 with VA ≥20/200 have also shown response to treatment. Results of major clinical trials are pending. CONCLUSION: PBT remains an emergent therapy with possible applications in DR and AMD. Further, high powered studies monitored by a neutral party with standard devices, treatment delivery and treatment timing are needed.

Angiopoietins as Potential Targets in Management of Retinal Disease.

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

Experimental evidence for maternal provisioning of alkaloid defenses in a dendrobatid frog.

Dendrobatid frogs sequester alkaloid defenses from dietary arthropods. Here, we provide experimental evidence that mother strawberry poison frogs (Oophaga pumilio) provision alkaloids to tadpoles. Captive-raised females were fed the synthetic alkaloid decahydroquinoline (DHQ), which we subsequently quantified in their skin, eggs, and developing tadpoles. DHQ quantity was positively associated with tadpole mass/development, suggesting high sequestration rates by tadpoles. These data confirm that tadpoles obtain nutrition and alkaloids by feeding exclusively on maternally provisioned eggs.

Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential.

Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that enhances both platelet responsiveness and in vivo thrombosis potential in animal models, and TMAO plasma levels predict incident atherothrombotic event risks in human clinical studies. TMAO is formed by gut microbe-dependent metabolism of trimethylamine (TMA) moiety-containing nutrients, which are abundant in a Western diet. Here, using a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme pair, CutC and CutD (CutC/D), we developed inhibitors that are potent, time-dependent, and irreversible and that do not affect commensal viability. In animal models, a single oral dose of a CutC/D inhibitor significantly reduced plasma TMAO levels for up to 3 d and rescued diet-induced enhanced platelet responsiveness and thrombus formation, without observable toxicity or increased bleeding risk. The inhibitor selectively accumulated within intestinal microbes to millimolar levels, a concentration over 1-million-fold higher than needed for a therapeutic effect. These studies reveal that mechanism-based inhibition of gut microbial TMA and TMAO production reduces thrombosis potential, a critical adverse complication in heart disease. They also offer a generalizable approach for the selective nonlethal targeting of gut microbial enzymes linked to host disease limiting systemic exposure of the inhibitor in the host.