Intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular oedema (DME) may begin with several initial monthly doses. Characteristics, treatment patterns and outcomes were compared for eyes with DME that did and did not receive such initial doses.
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.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.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).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.].
Background and Objective Liver health has been reported to be associated with retinal pathology in various ways. These include deposition of retino-toxins, neovascular drive, and disruption of the blood-retina barrier. Extrahepatic synthesis of implicated molecules and hemodynamic changes in liver dysfunction are also considered. The objective was to review the current evidence for and against a hepato-retinal axis that may guide further areas of preclinical and clinical investigation. Methods This was a systematic review. PubMed and Cochrane were queried for English language studies examining the connection between hepatic dysfunction and retinal pathology. Results Fourteen studies were included and examined out of 604 candidate publications. The studies selected include preclinical studies as well as clinical case series and studies. Conclusions Several liver pathologies may be linked to retinal pathology as mediated by hepatically synthesized molecules. The hepato-retinal axis may be present and further, targeted studies of the axis are warranted. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:587–596.]
Little is known about factors affecting risk or time to development of fellow eye retinal vein occlusion (RVO). The purpose of this study was to examine the incidence and risk factors for fellow eye RVO.This was a retrospective case-control study comparing unilateral and fellow eye RVO patients. This study was exempt by the Cleveland Clinic Institutional Review Board.Out of 1,083 patients, fellow eye RVO had a cumulative incidence of 3.6% (95% CI 2.61, 4.94) with a median time to development of 18 months (95% CI 6.0, 28.0). Fellow eye disease was associated with multiple characteristics including chronic kidney disease (odds ratio [OR] 3.78, 95% CI 1.89 to 7.55) and diabetic retinopathy (3.18, 1.57 to 6.44).While fellow eye RVO is relatively rare, it typically occurs within the first few years following initial diagnosis. Multiple characteristics were associated with fellow eye disease and time to onset. [Ophthalmic Surg Lasers Imaging Retina 2023;54:471-476.].
Abstract Background and objective Anti-vascular endothelial growth factor (VEGF) injections are often administered less frequently in real-world treatment of diabetic macular oedema (DMO) than what was studied in clinical trials. This study aims to characterise real-world DMO treatment patterns and the effect of treatment intervals on patient outcomes. Study design/patients and methods This was a retrospective study of 291 patients with DMO treated with anti-VEGF therapy. 12- and 24-month best visual acuity (BVA) and central subfield thickness (CST) were compared between injection interval groups, which were determined by averaging the two most recent injection intervals. Multiple linear regressions were performed to identify factors associated with injection interval, BVA, and CST. Results 48.8% of patients received injections less than or equal to every 8 weeks (≤ q8w), 27.5% between every 8 to 12 weeks (q8–12w), and 23.7% greater than every 12 weeks (> q12w). Baseline CST was similar ( p = 0.32), but BVA differed significantly in q8–12w patients ( p = 0.0095). BVA and CST at 12 months were similar, but q8–12w patients experienced greater 12-month BVA improvement (7.36 ± 12.4 letters) than > q12w patients (1.26 ± 12.3 letters; p = 0.0056). 24-month BVA and CST changes were similar between groups ( p = 0.30 and 0.87). Baseline BVA, HbA1c, and sex were associated with 12-month BVA, and baseline BVA and CST were associated with 12-month CST. Conclusion Many patients experienced improvements in BVA and CST over 12 months of treatment despite receiving less frequent anti-VEGF therapy than recommended in the pivotal trials. The present study showed that extended treatment intervals with bevacizumab were effective in preserving vision of many individuals with high baseline BVA.
Purpose of review To review the available data supporting the use of brolucizumab in the treatment of diabetic macular edema (DME). Recent findings Brolucizumab is a humanized single- chain variable antibody fragment (scFv), the smallest functional subunit of an antibody approved for intravitreal use. Three phase III studies demonstrate that at 52 weeks, brolucizumab has statistically superior anatomical outcomes of reducing retinal thickness (54.0–57.5% of brolucizumab treated eyes achieved central subfield thickness <280 μm compared to 40.1 – 41.4% of aflibercept treated eyes) and retinal fluid (present in 54.2–60.3% of brolucizumab treated eyes compared to 72.9–78.2% of aflibercept treated eyes). Brolucizumab also demonstrated a prolonged durability up to 16 weeks, thus reducing treatment burden. The visual outcomes appear noninferior to current anti-VEGF agents with an increased risk for intraocular inflammatory events (0.3–4.7% compared to 0.6–1.7%). Summary Results from recent phase III trials showing the efficacy and safety of brolucizumab presents an additional therapeutic option in the DME treatment landscape. It can reduce treatment burden in DME with increased inter-treatment intervals while conferring efficacy in both functional and anatomical outcomes. Caution should be taken regarding the risks of intraocular inflammation, retinal vasculitis, and retinal vascular occlusion.
To characterize and predict limited early responders (LER) in eyes with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (anti-VEGF).This retrospective cohort study of 116 eyes with edema secondary to RVO characterized early responders (ER) and LER 3 months after initiating anti-VEGF treatment. Baseline characteristics and 12-month outcomes were compared. A machine learning (ML) algorithm was developed to predict LER.At baseline, LER had higher best-corrected visual acuity (BCVA) than ER (P< 0.0001) and lower central subfield thickness (CST) than ER (P< 0.01). At 12 months, change in BCVA was + 0.8 and + 21.4 letters, and change in CST was -104.4 and -187.1 μm for LER and ER, respectively (P < 0.0001, P < 0.05). The ML algorithm achieved area under the receiver operating characteristic curve = 0.73.ER eyes experienced greater functional and anatomical improvements at 12 months in routine clinical practice than LER. The ML algorithm achieved moderately high performance predicting LER. [Ophthalmic Surg Lasers Imaging Retina 2023;54:231-237.].
The purpose of this study was to implement a clinical decision support tool (CDS) and assess its impact on adherence to 2016 American Academy of Ophthalmology (AAO) hydroxychloroquine dosing recommendations.This retrospective, interventional study implemented an automated alert to calculate maximum daily hydroxychloroquine dose based on 2016 AAO recommendations and flag noncompliant orders. Prevalence of excessive dosing after CDS implementation was assessed.A total of 7,417 patients met inclusion criteria. After intervention, prevalence of excessive dosing decreased from 27.4% to 21.1% (P < .001) among all prescriptions and from 26.8% to 16.2% (P < .001) among new prescriptions. Daily doses exceeding 400 mg decreased from 0.8% to 0.02% (P < .001). Risk factors for excessive dosing included low weight (odds ratio, 75.6 [95% CI, 54.0 to 105.8]) and nonrheumatologist prescriber (odds ratio, 1.60 to 3.63; all P < .005).This study highlights the efficacy of a CDS in reducing excessive hydroxychloroquine dosing and improving adherence to AAO ophthalmic safety guidelines. [Ophthalmic Surg Lasers Imaging 2022;53:310-316.].
Purpose : To implement and assess the impact of an electronic clinical decision support tool (DST) on prescriber adherence to 2016 Academy of Ophthalmology (AAO) recommendations for a hydroxychloroquine maximum daily dose of 5 mg/kg actual body weight. Methods : A DST was developed to trigger a pop-up alert within the electronic medical record when a prescriber orders hydroxychloroquine exceeding 5 mg/kg actual body weight or >400mg daily. The prescriber may choose to amend the prescription or override the alert. The tool was implemented on April 21, 2020. A chart review was performed of all hydroxychloroquine prescriptions in the 6-month post-intervention period (May - November 2020). Inclusion criteria were patient age ≥18 years;availability of dose and frequency;availability of actual body weight;and outpatient prescription status. Only the most recent prescription was used in cases of an individual patient having multiple prescriptions. Prevalence of excess hydroxychloroquine dosing (>5mg/kg/day) and mean daily dose in the post-intervention period was compared to previously collected, preintervention data from 2018 (under review for publication), using the chi-squared test and 2-sample t-test, respectively. The odds ratios of excessive dosing was assessed using multivariable logistic regression that included sex, race, weight, and prescriber specialty. Results : There were 7915 patients with active hydroxychloroquine prescription, of which 7415 (94%) met inclusion criteria. There prevalence of excessive dosing decreased from 27.4% pre-DST to 21.1% post-DST (P<0.001). Mean daily dose decreased from 342±94 mg (4.3±1.4 mg/kg/day) pre-DST to 324±93mg (4.1±1.3mg/kg/day) post-DST (P<0.001). Only 0.2% prescriptions exceeded mean 400mg daily, and 0.1% prescriptions were indicated for COVID-19. In multivariable analysis, a rheumatologist prescriber (in comparison to all other specialties, OR 0.66 [99% CI 0.54-0.80]) and greater weight (OR 0.94 [99% CI 0.93- 0.95], equivalent to -0.062 log odds per 1 kg increase in weight) were associated with reduced odds of excessive dosing. Conclusions : Implementation of a DST significantly improved prescriber adherence with 2016 AAO ophthalmic safety recommendations for hydroxychloroquine dosing. As daily dosage is a strong predictor of retinopathy risk, an electronic DST demonstrates potential to reduce ophthalmic morbidity associated with chronic hydroxychloroquine use.
