Retinal vein occlusion as an age-dependent marker of incident dementia in a long-term Danish national cohort.

PURPOSE: The aim of this study was to investigate retinal vein occlusion (RVO) as an independent marker of incident dementia. METHODS: In a prospective nationwide cohort study, we identified 2 225 568 individuals through the Danish national health registers. Individuals older than 65 years, without unspecified retinal vascular occlusion or dementia were included from 1998 to 2020 and followed until 2022. We calculated the incidence rate (IR) and performed a Cox regression analysis with a hazard ratio (HR) and 95% confidence interval (CI) for RVO (exposure) as a marker of all-cause dementia adjusted for systemic comorbidity. RESULTS: We identified 19 669 individuals with RVO who had a higher prevalence of systemic comorbidity at inclusion compared to those without RVO (n = 2 185 483). We performed a Cox regression analysis for age-dependent exposure due to non-proportional hazards in the pre-planned analysis. Exposed individuals younger than 75 years had an increased risk of all-cause dementia (adjusted HR 1.09, 95% CI 1.01-1.18), whereas individuals older than 75 years had a decreased risk of all-cause dementia (adjusted HR 0.92, 95% CI 0.86-0.98). CONCLUSION: Individuals with RVO had an age-dependent risk of dementia, with a 9% increased risk in individuals with RVO younger than 75 years and an 8% decreased risk in individuals older than 75 years at the time of exposure.

Retinal artery occlusion does not act as an independent marker of upcoming dementia: results from a Danish 20-year cohort study.

PURPOSE: Retinal artery occlusion (RAO) is a vision threatening disease associated with cerebral vascular dysfunction, which may reflect initial signs of cerebral pathology. Early detection of patients in risk of dementia could allow for preventative treatment. Hence, this study aimed to investigate RAO as an independent biomarker of incident dementia. METHODS: This study was a nationwide, 20-year longitudinal cohort study in Denmark with inclusion from 1998 to 2020 and follow up until the end of 2022. We identified 2 205 159 individuals aged 65 or older through the Danish national health registers and monitored RAO (exposure) and dementia (outcome) status. We calculated incidence rate and performed a Cox regression analysis with hazard ratio (HR) and 95% confidence interval (CI) for RAO as a marker of dementia in a crude, a semi-adjusted (age and sex), and a fully adjusted model (furthermore adjusted for marital status and systemic comorbidity.) RESULTS: We identified 8 863 individuals with RAO. Incidence rates were higher among exposed compared to unexposed individuals (12.28 and 8.18 per 1000 person-years at risk, respectively). Individuals with RAO were more likely to be male and older at inclusion, to have hypertension, dyslipidaemia, cardiovascular disease, chronic kidney disease, and diabetes (p < 0.001). RAO was not associated with all-cause dementia in the crude analysis (HR 1.07 CI [1.00-1.17]) or in the fully adjusted analysis (HR 0.98 CI [0.91-1.06]. CONCLUSION: Although individuals with RAO had a higher incidence of dementia compared to unexposed individuals, these associations were lost when confounders were taken into account.

Predictive value of retinal oximetry, optical coherence tomography angiography and microperimetry in patients with treatment-naïve branch retinal vein occlusion.

Vascular endothelial growth factor inhibitors have substantially improved the visual outcomes in patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), but treatment outcomes are highly variable and early prediction of expected clinical outcome would be important for individualized treatment.As non-invasive metabolic, structural and functional retinal markers might act as early predictors of clinical outcomes, we performed a 12-month, prospective study aimed to evaluate if baseline retinal oximetry, optical coherence tomography angiography (OCT-A) or microperimetry were able to predict need of treatment, structural or functional outcome in patients with ME caused by treatment-näive BRVO.We evaluated 41 eyes of 41 patients with a mean age of 69.6 years and 56% females. We found a strong tendency towards a higher retinal arteriolar oxygen saturation in patients without a need of additional aflibercept treatment after the loading phase (99.8% vs. 92.3%, adjusted odds ratio 0.80 (95% confidence interval 0.64-1.00), adjusted p = 0.058), but otherwise, retinal oximetry, OCT-A or microperimetry were not able to predict need of treatment, structural nor functional outcomes. (Trial registration: clinicaltrials.gov, S-20,170,084. Registered 24 August 2014, https://clinicaltrials.gov/ct2/show/NCT03651011 ).

VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality.

PURPOSE: Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. DESIGN: A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. SUBJECTS: Patients with RVO (n = 7235), exposed (n = 3508), and unexposed (n = 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. METHODS: Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. MAIN OUTCOME MEASURES: A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. RESULTS: We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89-1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77-1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02-2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. CONCLUSION: Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Cardiovascular morbidity and all-cause mortality in patients with retinal vein occlusion: a Danish nationwide cohort study.

BACKGROUND/AIMS: Associations between retinal vein occlusion (RVO) and subsequent cardiovascular disease (CVD) or mortality have not been evaluated in a recent cohort, after novel therapeutic options have increased referrals for treatment of the condition. We aimed to evaluate overall and subtype-stratified risk of CVD and all-cause mortality following RVO and assess any alterations after the introduction of angiostatic therapy in Denmark in 2011. METHODS: This nationwide, registry-based cohort study from 1998 to 2018 evaluated 4 194 781 individuals. Hazard ratios (HRs) were reported for RVO as an overall measure and subclassified as branch and central RVO. RESULTS: Patients with RVO (n=15 665) were median 71.8 years old at the time of exposure and 50.7% were women. RVO associated with incident CVD (adjusted HR 1.13, 95% CI 1.09 to 1.17) but not mortality (adjusted HR 1.00, 95% CI 0.97 to 1.03). Almost similar risks of CVD were found for patients with branch and central RVO (adjusted HRs 1.14, 95% CI 1.03 to 1.25, and 1.12, 95% CI 1.00 to 1.25, respectively), but only patients with central RVO exhibited increased mortality (adjusted HR 1.12, 95% CI 1.04 to 1.21). Risk of CVD, especially non-ischaemic, was higher for patients diagnosed after 2011 (adjusted HRs 1.24, 95% CI 1.15 to 1.33 vs 1.06, 95% CI 1.01 to 1.12). CONCLUSION: In a cohort of the Danish population aged 40 years or more, patients with RVO had a 13% increased risk of incident CVD compared with unexposed individuals. Risk of CVD was increased after 2011, when intravitreal angiostatic treatment was introduced and referral practices altered.

Navigated laser and aflibercept versus aflibercept monotherapy in treatment-naïve branch retinal vein occlusion: A 12-month randomized trial.

PURPOSE: Angiostatic agents have proven effective in the treatment of macular oedema in patients with branch retinal vein occlusion (BRVO). However, treatment is inconvenient and expensive, and novel treatment regimens are warranted. We aimed to evaluate if combination treatment of navigated central retinal laser and aflibercept lowered the treatment burden in these patients. METHODS: Treatment-naïve patients with BRVO and macular oedema were included at two centres and randomized 1:1 to three monthly injections of 2.0 mg aflibercept with (Group A) or without (Group B) navigated central laser, followed by aflibercept as needed from month 4 through 12. Re-treatment need was evaluated, and secondary endpoints included functional and anatomical outcomes and safety evaluated by retinal microperimetry. RESULTS: We evaluated 41 eyes of 41 patients with a mean age of 69.6 years. Baseline median best-corrected visual acuity (BCVA) was 70.0 letters, and median central retinal thickness (CRT) was 502 µm with no difference between Groups A (n = 21) and B (n = 20). Percentage of patients needing re-treatment after month three was 71% and 80% (p = 0.72). At month 12, groups did not differ in number of injections after loading (1 versus 2, p = 0.43), change in BCVA (+12.8 versus +15.1 letters, p = 0.48), CRT (-195 versus -181 µm, p = 0.82), or retinal sensitivity (+3.3 versus +4.1 dB, p = 0.67). CONCLUSION: In treatment-naïve BRVO patients, addition of navigated central laser to aflibercept did not lower treatment burden or affect functional or anatomical outcomes. A low number of intravitreal injections were needed for successful outcome in both treatment arms.

Is there still a role of macular laser treatment in branch retinal vein occlusion in the era of intravitreal injections?

We aimed to evaluate whether macular laser still has a role in the treatment of macular oedema (MO) caused by branch retinal vein occlusion (BRVO) and provide an overview of recent studies on commonly available treatment options. A literature search was last conducted in PubMed on 26 February 2019, limited to human randomized controlled trials published in English since 2008. Seventeen articles addressing 13 trials were included in this assessment. In trials evaluating intravitreal corticosteroid and macular laser, triamcinolone was non-inferior to laser in regard to visual acuity (VA) and central retinal thickness (CRT) outcomes. Combination treatment of dexamethasone and laser resulted in better VA and lower CRT after 6 months. In trials evaluating vascular endothelial growth factor (VEGF) inhibitors versus macular laser treatment, or sham and rescue laser, better VA and CRT of VEGF inhibition treatment was consistently reported. Results of combination treatment versus VEGF inhibition monotherapy were inconsistent, with four of six studies reporting comparable outcomes and injection burden. Study comparison was affected by considerable differences in study design and inadequate reporting of laser protocol and rescue laser. Studies evaluating angiostatic treatment as monotherapy largely report the use of rescue laser, indicating that some patients would benefit from supplemental laser treatment even in the era of intravitreal therapy. Thus, we suggest further studies on optimal design of combination therapy prioritizing longer follow-up time to sufficiently evaluate the delayed effect of laser.

Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study.

OBJECTIVE, DESIGN AND METHODS: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points. RESULTS: After a 24.1% mean weight loss from baseline to month 12 (P < 0.001), body weight plateaued from month 12 to 24 (-0.9%, P = 0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P < 0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24. CONCLUSIONS: Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.