The role of phacoemulsification surgery in the incidence rate of rhegmatogenous retinal detachment.

PURPOSE: To investigate changes in the incidence rate of primary rhegmatogenous retinal detachment (RRD) surgery over time and to determine to what extent these changes can be attributed to pseudophakia. METHODS: This nationwide cohort study was based on national patient registries. The study population comprised individuals at risk of RRD aged 40 years and above from 2006 to 2021 in Denmark. The primary outcome was RRD incidence, and the exposure was phacoemulsification surgery. A chart review was conducted to validate and examine the lens status of the outcome. RESULTS: The crude and age-adjusted incidence rate of RRD in the Danish population increased significantly during the study period. The largest increase in RRD was seen in phakic RRD (phRRD) (65%), whereas pseudophakic RRD (pRRD) accounted for 35% of the total increase. A chart review revealed that 17% of phRRDs were misclassified as pseudophakic, resulting in pRRD accounting for a total of 45% of the increase in RRD. The prevalence of pseudophakia in Denmark grew significantly for all age groups and for both sexes (p = 10-6) from 2006 to 2021, but the 1-year incidence of pRRD in the pseudophakic population was constant throughout the entire period. CONCLUSION: The incidence rate of RRD is continuing to increase in Denmark. The increase in phRRD remains undetermined, and while the risk of pRRD seemed to be constant during the study period, 45% of the overall increase in RRD could be attributed to the rise of a growing pseudophakic population.

Risk of Diabetic Retinopathy According to Subtype of Type 2 Diabetes.

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of ß-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR.

VEGF Inhibition Associates With Decreased Risk of Mortality in Patients With Neovascular Age-related Macular Degeneration.

Purpose: Controversy exists regarding the systemic safety of intravitreal VEGF inhibitors in the treatment of neovascular age-related macular degeneration (nAMD). We aimed to investigate the potential impact of VEGF inhibitor treatment on the risk of all-cause mortality and cardiovascular disease (CVD) among patients with nAMD. Design: A nationwide register-based cohort study with 16 years follow-up. Participants: Patients with nAMD exposed with VEGF inhibitors (n = 37 733) and unexposed individuals without nAMD (n = 1 897 073) aged ≥ 65 years residing in Denmark between January 1, 2007, and December 31, 2022. Methods: Cox proportional hazards analysis was conducted to assess the effect of intravitreal VEGF inhibitor treatment on all-cause mortality and incident CVD. Main Outcome Measures: In a predefined analysis plan we defined primary outcomes as hazard ratios (HRs) of all-cause mortality and a composite CVD endpoint in patients with nAMD treated with VEGF inhibitors compared with individuals without nAMD. The secondary outcomes encompassed analyses that explored the impact of the number of doses and the association between exposure and outcome over a specific time period. Results: Overall, 63.7% of patients with nAMD were women with an average age of 69.9 years (interquartile range 65.0-76.0 years). Patients exposed to VEGF inhibitors demonstrated a reduced risk of all-cause mortality compared with individuals without nAMD (HR, 0.79; 95% confidence interval [CI], 0.78-0.81), and an increased risk of composite CVD (HR, 1.04; 95% CI, 1.01-1.07). The decreased risk of all-cause mortality persisted, but there was no significant association between VEGF inhibitor treatment and CVD when patients with nAMD were grouped by the number of doses or considered exposed within 60 days postinjection. Conclusions: Our study revealed a decreased risk of all-cause mortality and a 4% increased risk of CVD among patients with nAMD exposed with VEGF inhibitors. The decreased risk of mortality is unlikely to be directly pathophysiologically related to VEGF inhibitor treatment. Instead, we speculate that patients undergoing VEGF inhibitor treatment are, on average, individuals in good health with adequate personal resources. Therefore, they also have a higher likelihood of overall survival. These findings strongly support the safety of VEGF inhibitor treatment in terms of all-cause mortality and CVD among patients with nAMD. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Patient perspectives and barriers in the treatment of neovascular age-related macular degeneration in Denmark: a qualitative study.

OBJECTIVES: This qualitative study aims to identify patient-reported barriers to treatment for neovascular age-related macular degeneration (nAMD) and investigate their impact on quality of life. DESIGN: Using a qualitative explorative design. SETTING: Semi-structured individual or dyadic interviews were conducted with patients and their relatives. PARTICIPANTS: Twenty-one patients completed the interview, with four of them having a relative present. INTERVENTIONS: Gadamer's hermeneutics guided the epistemological approach, and maximum variation sampling was employed to capture diverse patient experiences. An advisory board consisting of patients, relatives and ophthalmologists ensured the relevance of the study. Thematic analysis was conducted using NVivo software. PRIMARY AND SECONDARY OUTCOME MEASURES: To investigate patient-reported barriers to the recommended treatment for nAMD and impact on quality of life. RESULTS: The study included 21 patients with nAMD, with a median age of 79 years. Five themes emerged: (1) good compliance with intravitreal treatment, (2) the dual role of relatives, (3) treatment commute, (4) hospital barriers, (5) preventive health literacy. CONCLUSION: This study highlights the resilience and adherence of patients with nAMD in Denmark to their treatment despite various barriers. While the therapy may have negative effects on their well-being, patients do not opt out of treatment. These findings underscore the importance of personalised treatment plans that provide, for example, convenient access to care and clear future agreements at the hospital. By adopting more patient-centred approaches, healthcare providers can enhance patient satisfaction and improve treatment adherence, ultimately leading to better patient outcomes and quality of life.

Intravitreal Vascular Endothelial Growth Factor Inhibitor Therapy in Denmark and 5-Year Projections.

This cohort study examines the use of intravitreal injections of vascular endothelial growth factor inhibitor in Denmark from 2007 through 2022 and forecasts future demand for this therapy.

Prevalence of geographic atrophy in Nordic countries and number of patients potentially eligible for intravitreal complement inhibitor treatment: A systematic review with meta-analyses and forecasting study.

We systematically reviewed the literature on the prevalence of geographic atrophy (GA) in Nordic populations, conducted meta-analyses on age-stratified estimates, and calculated current and future number of patients and those potentially eligible for intravitreal complement inhibitor treatment. We followed the PRISMA guidelines, and our protocol was registered in PROSPERO. Ten databases were searched on 22 April 2023 for population-based studies of GA prevalence. Based on clinical descriptive analyses of GA and eligibility criteria of the phase III studies for intravitreal pegcetacoplan (complement C3 and C3b inhibitor), we were able to calculate the proportion of patients with GA potentially eligible for therapy. Finally, we extracted population data for Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, applied prevalence statistics to the extracted census and forecasting data to estimate the number of patients with GA, and then applied the proportion eligible for intravitreal pegcetacoplan therapy. We identified six studies with a total of 10 159 individuals. Prevalence of GA was estimated to 0.4% (95% confidence intervals [CI]: 0.2%-0.8%), 1.5% (95% CI: 0.7%-2.6%), and 7.6% (95% CI: 4.6%-11.3%) for individuals aged 60-69, 70-79, and 80+ years, respectively. In Nordic countries, we estimate a total of 166 307 individuals with GA in 2023, increasing to 277 893 in 2050. Of these, 90 803 individuals in 2023, increasing to 151 730 in 2050, are potentially eligible for intravitreal complement inhibitor treatment. Considering these large numbers, our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing.

Diabetic retinopathy is a predictor of chronic respiratory failure: A nationwide register-based cohort study.

Purpose: Diabetic retinopathy (DR) is a hypoxic retinal disease, but so far, the association with systemic hypoxia is poorly understood. Hence, the aim of this study was to evaluate cross-sectional and longitudinal associations between DR and chronic respiratory failure (CRF) in a national cohort. Design: Cross-sectional and 5-year longitudinal register-based cohort study. Methods: Between 2013 and 2018, we included patients with diabetes from the Danish Registry of Diabetic Retinopathy, who were each age and sex matched with five controls without diabetes. At index date, the prevalence of CRF was compared between cases and controls, and the longitudinal relationship between DR and CRF was assessed in a five-year follow-up. Results: At baseline, we identified 1,980 and 9,990 patients with CRF among 205,970 cases and 1,003,170 controls. The prevalence of CRF was higher among cases than controls (OR 1.75, 95% CI 1.65-1.86), but no difference between cases with and without DR was found.During follow-up, we identified 1,726 and 5,177 events of CRF among cases and controls, respectively. The incidence of CRF was higher among both cases with and without DR compared to controls (DR level 0: HR 1.24, 95% CI 1.16-1.33, DR level 1-4: HR 1.86, 95% CI 1.63-2.12), and higher among cases with DR compared to cases without DR (HR 1.54, 95% CI 1.38-1.72). Conclusion: In this study based on nationwide data, we found an increased risk of present and incident CRF in patients with diabetes with or without DR, and we identified DR as a predictor of future CRF.

Association between oral metformin use and the risk of age-related macular degeneration: A systematic review with meta-analysis.

Rodent studies demonstrate that oral metformin use may reduce chronic low-grade inflammation, downregulate apoptosis and extend life span. Emerging epidemiological evidence suggests that oral metformin use may protect against development of age-related macular degeneration (AMD) in humans. In this study, we systematically reviewed the literature on the association between oral metformin use and AMD in patients with type 2 diabetes and conducted a quantitative meta-analysis to provide a summary estimate of the association. We searched 12 literature databases on 10 August 2022 and identified nine eligible studies with data on a total of 1 427 074 individuals with diabetes. We found that patients with diabetes using metformin had a significantly lower odds ratio (OR) of having or developing AMD (OR 0.63; 95% CI: 0.46-0.86; p = 0.004). Our analyses also revealed that although the findings were robust in the sensitivity analysis, the Funnel plot indicated a certain publication bias towards finding a protective effect. Results of individual studies suggested inconsistent findings, as some studies found lower risk of AMD from higher total metformin exposure, whereas other studies found a higher risk of AMD from higher total metformin exposure. Taken together, there may be a link between metformin use and lower risk of AMD, but the relationship is only studied in observational studies, various sources of bias can be speculated to influence, and careful interpretation is warranted.

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.

[Preseptal cellulitis to suspected odontogenic origin treated with intensive therapy].

A 55-year-old woman was hospitalised due to sudden redness and swelling around the left eye as well as malaise. Prior to hospitalisation, the patient was treated with antibiotics because of a dental infection. The patient was admitted to the hospital for more than three weeks and received intravenous antibiotics, which was changed several times due to treatment failure. After three weeks, she had a rooted tooth removed and she was discharged within days. Preseptal cellulitis as a complication to odontogenic infection can develop into a critical and life-threatening condition.

Effect of transanal total mesorectal excision for rectal cancer: comparison of short-term outcomes with laparoscopic and open surgeries.

OBJECTIVE: To compare short-term results of total mesorectal excision (TME) for mid and low rectal cancer, achieved by transanal (TaTME), laparoscopic (LaTME), and open (OpTME) approaches. BACKGROUND: The impact of TaTME on the surgical treatment of mid and low rectal cancer has yet to be clarified. METHODS: This is a case-matched study, based on data from a prospectively maintained database of patients who underwent TaTME from May 2015 to March 2017, and a retrospective chart review of patients who underwent LaTME and OpTME in the previous period. Each patient in the TaTME group was matched to one LaTME and one OpTME based on sex, BMI, tumor status, and the height of the tumor from the anal verge. Primary end-points were rates of positive circumferential resection margin (CRM), distal resection margin, and the macroscopic quality of the surgical specimen. Composite of these outcomes was compared as an indication for successful surgery. Secondary end-points included intraoperative data and postoperative course and complications. RESULTS: Three hundred patients were included (TaTME = 100, LaTME = 100, OpTME = 100). The three groups were comparable in the baseline characteristics. TaTME resulted in lower rates of incomplete TME specimens than LaTME, but not OpTME (P = 0.016, P = 0.750, respectively). The rates of CRM involvement, mean CRM distance, and the percentages of successful surgery were comparable among the three groups (P = 0.368). The conversion to open surgery occurred only in the LaTME group. TaTME resulted in shorter operation time and less blood loss than the other two groups (P < 0.001 and P < 0.001). Hospital stay was shorter in the TaTME group (P = 0.002); complication rate and mortality were comparable among the groups. CONCLUSIONS: TaTME had, in our hands, some obvious benefits over other approaches. The pathological results were not significantly superior to LaTME and OpTME. The procedure is however feasible and safe. Further studies are needed to evaluate the long-term oncological and quality of life outcomes.