The epidemiology of uveal melanoma in Germany: a nationwide report of incidence and survival between 2009 and 2015

Purpose: To calculate the overall incidence of uveal melanoma in Germany and to compare incidences in different German states. In addition, we computed the overall and cancer-specific survival rates nationwide. Methods: Incidence data for the period between 2009 and 2015, covering the entire German population, was collected through the German Center for Cancer Registry. ICD-O-3 topography codes C69.3-C69.4 and histology codes for melanoma subtypes were used to collect the incidence data. Confidence Intervals with a level of 95% (95% CI) were calculated for rates. Survival was calculated using the Kaplan–Meier. The log-rank test was used for survival comparisons. Results: This study comprised 3654 patients with uveal melanomas, including 467 (12.8%) with iridial and ciliary body tumors. The overall age-standardized incidence rate (ASIR) was 6.41 person per million. Generally, the ASIR was higher in males than females (6.67 (95% CI 6.37–6.98) vs. 6.16 (95% CI 5.88–6.45 per million). Higher crude incidence rates were noted in the northeastern states (12.5 per million (95% CI 10.5–14.7) in Mecklenburg-Vorpommern) compared with the southwestern states (2.1 per million (95% CI 1.7–2.6) in Hessen). The 5-year overall survival stood at 47%, while the cancer-specific survival stood at 84%. Multivariate analysis showed that women, younger patients, and patients living in Berlin achieved significantly higher overall survival. Conclusion: Overall ASIR of uveal melanoma in Germany indicates that the disease is more common in males and that it follows the same geographical distribution previously noted in central European countries, with the highest incidence in northern parts of Germany

FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration

Background: Forkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive T cells into Tregs that can downregulate the effector function of other T cells. We previously detected the expression of FoxP3 in retinal pigment epithelial (RPE) cells, forming the outer blood-retina barrier of the immune privileged eye. Methods: We investigated the expression, subcellular localization, and phosphorylation of FoxP3 in RPE cells in vivo and in vitro after treatment with various stressors including age, retinal laser burn, autoimmune inflammation, exposure to cigarette smoke, in addition of IL-1 beta and mechanical cell monolayer destruction. Eye tissue from humans, mouse models of retinal degeneration and rats, and ARPE-19, a human RPE cell line for in vitro experiments, underwent immunohistochemical, immunofluorescence staining, and PCR or immunoblot analysis to determine the intracellular localization and phosphorylation of FoxP3. Cytokine expression of stressed cultured RPE cells was investigated by multiplex bead analysis. Depletion of the FoxP3 gene was performed with CRISPR/Cas9 editing. Results: RPE in vivo displayed increased nuclear FoxP3-expression with increases in age and inflammation, long-term exposure of mice to cigarette smoke, or after laser burn injury. The human RPE cell line ARPE-19 constitutively expressed nuclear FoxP3 under non-confluent culture conditions, representing a regulatory phenotype under chronic stress. Confluently grown cells expressed cytosolic FoxP3 that was translocated to the nucleus after treatment with IL-1 beta to imitate activated macrophages or after mechanical destruction of the monolayer. Moreover, with depletion of FoxP3, but not of a control gene, by CRISPR/Cas9 gene editing decreased stress resistance of RPE cells. Conclusion: Our data suggest that FoxP3 is upregulated by age and under cellular stress and might be important for RPE function

Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study

Background: To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990–2020, and forecasts for 2050. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals [UIs]) of mild vision impairment (presenting visual acuity ≥6/18 and <6/12), moderate and severe vision impairment (<6/18 to 3/60), and blindness (<3/60 or less than 10° visual field around central fixation); and vision impairment from uncorrected presbyopia (presenting near vision <N6 or <N8 at 40 cm where best-corrected distance visual acuity is ≥6/12). We forecast estimates of vision loss up to 2050. Findings: In 2020, an estimated 43·3 million (95% UI 37·6–48·4) people were blind, of whom 23·9 million (55%; 20·8–26·8) were estimated to be female. We estimated 295 million (267–325) people to have moderate and severe vision impairment, of whom 163 million (55%; 147–179) were female; 258 million (233–285) to have mild vision impairment, of whom 142 million (55%; 128–157) were female; and 510 million (371–667) to have visual impairment from uncorrected presbyopia, of whom 280 million (55%; 205–365) were female. Globally, between 1990 and 2020, among adults aged 50 years or older, age-standardised prevalence of blindness decreased by 28·5% (–29·4 to −27·7) and prevalence of mild vision impairment decreased slightly (–0·3%, −0·8 to −0·2), whereas prevalence of moderate and severe vision impairment increased slightly (2·5%, 1·9 to 3·2; insufficient data were available to calculate this statistic for vision impairment from uncorrected presbyopia). In this period, the number of people who were blind increased by 50·6% (47·8 to 53·4) and the number with moderate and severe vision impairment increased by 91·7% (87·6 to 95·8). By 2050, we predict 61·0 million (52·9 to 69·3) people will be blind, 474 million (428 to 518) will have moderate and severe vision impairment, 360 million (322 to 400) will have mild vision impairment, and 866 million (629 to 1150) will have uncorrected presbyopia. Interpretation: Age-adjusted prevalence of blindness has reduced over the past three decades, yet due to population growth, progress is not keeping pace with needs. We face enormous challenges in avoiding vision impairment as the global population grows and ages

Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study

Background: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older. Findings: Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change −0·2% [95% UI −1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by −15·4% [–16·8 to −14·3], while avoidable MSVI showed no change (0·5% [–0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7–18·0]), followed by glaucoma (3·6 million cases [2·8–4·4]), undercorrected refractive error (2·3 million cases [1·8–2·8]), age-related macular degeneration (1·8 million cases [1·3–2·4]), and diabetic retinopathy (0·86 million cases [0·59–1·23]). Leading causes of MSVI were undercorrected refractive error (86·1 million cases [74·2–101·0]) and cataract (78·8 million cases [67·2–91·4]). Interpretation: Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached. Funding: Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg

The epidemiology of uveal melanoma in Germany: a nationwide report of incidence and survival between 2009 and 2015

Purpose!#!To calculate the overall incidence of uveal melanoma in Germany and to compare incidences in different German states. In addition, we computed the overall and cancer-specific survival rates nationwide.!##!Methods!#!Incidence data for the period between 2009 and 2015, covering the entire German population, was collected through the German Center for Cancer Registry. ICD-O-3 topography codes C69.3-C69.4 and histology codes for melanoma subtypes were used to collect the incidence data. Confidence Intervals with a level of 95% (95% CI) were calculated for rates. Survival was calculated using the Kaplan-Meier. The log-rank test was used for survival comparisons.!##!Results!#!This study comprised 3654 patients with uveal melanomas, including 467 (12.8%) with iridial and ciliary body tumors. The overall age-standardized incidence rate (ASIR) was 6.41 person per million. Generally, the ASIR was higher in males than females (6.67 (95% CI 6.37-6.98) vs. 6.16 (95% CI 5.88-6.45 per million). Higher crude incidence rates were noted in the northeastern states (12.5 per million (95% CI 10.5-14.7) in Mecklenburg-Vorpommern) compared with the southwestern states (2.1 per million (95% CI 1.7-2.6) in Hessen). The 5-year overall survival stood at 47%, while the cancer-specific survival stood at 84%. Multivariate analysis showed that women, younger patients, and patients living in Berlin achieved significantly higher overall survival.!##!Conclusion!#!Overall ASIR of uveal melanoma in Germany indicates that the disease is more common in males and that it follows the same geographical distribution previously noted in central European countries, with the highest incidence in northern parts of Germany

In-Depth Analysis of Incidence and Survival of Lacrimal Gland Malignancies in the United States of America from 1995 to 2018

To investigate lacrimal gland malignancies’ incidence and survival rates in the USA between 1995 and 2018. Incidence and survival data from the North American Association of Central Cancer Registries of lacrimal gland malignancies between 1996 and 2018 were extracted and analyzed. This study analyzed data pertaining to 3620 patients (females 56.7%, n = 2051). A sizable number of patients were 60–79 years of age (45.1%, n = 1633), with a substantial majority being of the non-Hispanic white ethnicity (82.9%, n = 3002). A little above half of patients (52.1%, n = 1886) had presented with a localized disease. Lymphomas represented 59.3% (n = 2146) of lacrimal gland malignancies, while 37% (n = 1339) were carcinomas. The cumulative age-adjusted incidence rate per million was 0.53 for all malignancies, 0.31 for lymphomas, and 0.2 for carcinomas. While the annual crude incidence rate showed a significant steady increase (average annual change of 1.24%; P  Early detection and localized tumor management can improve survival outcomes for patients with lacrimal gland malignancies. Further research is needed to understand these malignancies’ risk profiles and develop more effective treatment strategies.</p

Second primary malignancies of eye and ocular adnexa after a first primary elsewhere in the body

Purpose!#!The eye and its adnexal structures can give rise to first or consecutive primary malignancies or to encounter metastasis. Our aim was to define the characteristics of the second primary neoplasms affecting the eye and its adnexa and find the risk modifying factors for them after malignancies elsewhere in the body.!##!Methods!#!We have queried the Surveillance, Epidemiology and End-Results 'SEER'-9 program of the National Cancer Institute for the malignancies of the eye and its adnexa that occurred between 1973 and 2015. The malignancies were ordered chronologically according to their incidence: first or second primary malignancies. The tumors were classified according to ICD-O-3 classification. Standardized incidence ratios (SIR) and survival probabilities were calculated for subgroups.!##!Results!#!Among 3,578,950 cancer patients, 1203 experienced a second malignancies of the eye and its adnexa. The first malignancy was diagnosed between 50 and 69 years of age in 58.94% of them. The eyelid showed 280 events, while 50 in lacrimal gland, 181 in the orbit, 21 in the overlapping lesions, 15 in optic nerve, 148 in the conjunctiva, 9 in the cornea, 6 in the Retina, 379 in the choroid, and 93 in the ciliary body. The SIR of a second malignancy after a prior non-Hodgkin lymphoma was 2.42, and in case of previous skin carcinomas it was 3.02, melanoma of skin, and 2.13 and 1.58 in oral cavity/pharynx malignancies. The second ocular and adnexal neoplasms increased steadily over the 5-year periods on contrary to first primary neoplasms. The survival of patients affected with first ocular and adnexal neoplasms was significantly higher than those with second ocular and adnexal neoplasms. On the other side, second primary ocular and adnexal tumors showed a better survival than second primary malignancies elsewhere.!##!Conclusions!#!The epidemiological differences between first and second ocular and adnexal primaries suggest different underlying mechanisms. Careful ocular examination should be integrated in the long-term follow-up plan of cancer patients. Special attention should be given to patients with non-Hodgkin's lymphoma and melanoma as first primary