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Women with postmenopausal bleeding who present with an endometrial thickness 4 mm or less are at a very low risk of endometrial cancer, and therefore refraining from endometrial sampling in these women is considered justified. If the endometrial thickness is more than 4 mm, endometrial sampling is indicated to exclude endometrial cancer. Although women with a histological finding of endometrial hyperplasia without atypia have a slightly increased risk of developing endometrial cancer, this finding is generally regarded as a reassuring histology without the need for further follow-up. A recently published prospective cohort study reported that in 84 (29.8%) of 356 women presenting with postmenopausal bleeding and endometrial thickness of more than 4 mm, outpatient endometrial sampling failed because the amount of tissue was insufficient for a reliable histopathologic diagnosis. When endometrial sampling fails, there is currently no consensus on what to do. No long-term follow-up studies have reported the incidence of endometrial cancer after failure of endometrial sampling. The aim of this long-term cohort follow-up study was to investigate the relative risk of developing endometrial cancer after initial workup for postmenopausal bleeding shows reassuring histology or insufficient endometrial sampling. The authors hypothesized that women with postmenopausal bleeding and failure of endometrial sampling have an increased risk of endometrial (pre)malignancies. Participants were women with postmenopausal bleeding presenting at 3 hospitals in the Netherlands between January 2009 and April 2011. Long-term follow-up data were collected from the patient charts of the 3 participating hospitals and from PALGA, the Dutch Pathology Registry. Standardized incidence ratios were calculated to estimate the risk of endometrial cancer, relative to the general population. A total of 668 women presented with postmenopausal bleeding; of these, 568 were available for follow-up. Median follow-up time was 47 months (range, 7–63 months). Women with postmenopausal bleeding, endometrial thickness of more than 4 mm, and hyperplasia without atypia on biopsy at the first presentation had a 17 times increased risk of developing endometrial cancer during the first 4 years of follow-up compared with the age-specific population; the standardized incidence ratio was 17.15, with a 95% confidence interval of 1.96 to 61.93. All women who developed endometrial cancer after initial reassuring histology presented with recurrent postmenopausal bleeding. During follow-up, no endometrial cancer was diagnosed in women with endometrial thickness of more than 4 mm and no or insufficient histology at initial presentation. Despite an initial reassuring histological finding of endometrial hyperplasia without atypia, women with postmenopausal bleeding and endometrial thickness of more than 4 mm had a significantly increased risk of endometrial cancer during 4 years of follow-up compared with the age-specific population. Further studies are needed to determine whether additional diagnostics or a more stringent follow-up regimen would be cost-effective.

Age-related macular degeneration (AMD) is a vision impairing disease of the central retina characterized by early and late forms in individuals older than 50 years of age. However, there is little knowledge to what extent also younger adults are affected. We have thus set out to estimate the prevalence of early AMD features and late AMD in a general adult population by acquiring color fundus images in 2,840 individuals aged 25 to 74 years of the Cooperative Health Research in the Region of Augsburg project (KORA) in South Germany. Among the 2,546 participants with gradable images for each eye, 10.9% (n = 277) had early AMD features (applying the 9-step Age-Related Eye Disease Study Severity Scale), 0.2% (n = 6) had late AMD. Prevalence increased with age, reaching 26.3% for early AMD features and 1.9% for late AMD at the age 70+. However, signs of early AMD were found in subjects as young as 25 years, with the risk for early AMD features increasing linearly by years of age in men, and, less consistent with a linear increase, in women. Risk for early AMD features increased linearly by pack years of smoking in men, not in women, nor was there any association with other lifestyle or metabolic factors. By providing much sought-after prevalence estimates for AMD from Central Europe, our data underscores a substantial proportion of the adult population with signs of early AMD, including individuals younger than 50 years. This supports the notion that early AMD features in the young might be under-acknowledged.

Importance: It has been suggested that systemic inflammation increases the risk of age-related macular degeneration (AMD). Given that chronic immune modulation is present in patients with myeloproliferative neoplasms (MPNs), the risk of AMD in these patients may be increased.Objective: To compare the risk of AMD in patients with MPNs with the risk of AMD in matched controls from the general population.Design, Setting, and Participants: A nationwide population-based cohort study using Danish registers was conducted of all patients in Denmark who received a diagnosis between January 1, 1994, and December 31, 2013, of essential thrombocythemia, polycythemia vera, myelofibrosis, or unclassifiable MPNs. For each patient, 10 age- and sex-matched controls were included. All patients without prior AMD were followed up from the date of diagnosis (or corresponding entry date for the controls) until the first AMD diagnosis, death or emigration, or December 31, 2013, whichever occurred first. Data analysis was performed from April 1, 2015, to October 31, 2016.Main Outcomes and Measures: Incidence of AMD recorded in specialized hospital-based care. The rates and absolute risk of AMD were calculated. Using Cox proportional hazards regression models, smoking and risk-time adjusted hazard ratios (HRs) between patients and controls were calculated. In addition, HRs of neovascular AMD after 2006 were calculated since antivascular endothelial growth factor treatment was introduced nationwide at hospitals thereafter.Results: A total of 7958 patients with MPNs (4279 women [53.8%] and 3679 men [46.2%]; mean [SD] age at diagnosis, 66.4 [14.3] years) were included in the study. The rate of AMD per 1000 person-years at risk was 5.2 (95% CI, 4.6-5.9) for patients with MPNs (2628 with essential thrombocythemia, 3063 with polycythemia vera, 547 with myelofibrosis, and 1720 with unclassifiable MPNs) and 4.3 (95% CI, 4.1-4.4) for the 77445 controls, while the 10-year risk of AMD was 2.4% (95% CI, 2.1%-2.8%) for patients with MPNs and 2.3% (95% CI, 2.2%-2.4%) for the controls. The risk of AMD was increased overall for patients with MPNs (adjusted HR, 1.3; 95% CI, 1.1-1.5), with adjusted HRs for the subtypes of 1.2 (95% CI, 1.0-1.6) for essential thrombocythemia, 1.4 (95% CI, 1.2-1.7) for polycythemia vera, 1.7 (95% CI, 0.8-4.0) for myelofibrosis, and 1.5 (95% CI, 1.1-2.1) for unclassifiable MPNs. In addition, patients with MPNs had a higher risk of neovascular AMD (adjusted HR, 1.4; 95% CI, 1.2-1.6).Conclusions and Relevance: Our results suggest that patients with MPNs are at increased risk of AMD, supporting the possibility that systemic inflammation is involved in the pathogenesis of AMD.