Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14

Grand Challenges in global eye health: a global prioritisation process using Delphi method

Background We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenge

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Rod Densitomefry in the Aging Human Eye

Retinal densitometry is a noninvasivc physiologic technique used to examine the visual pigments in living human eyes. To assess possible age-related disturbances of rod photopigment kinetics, retinal densitometry was done in 44 eyes of 44 healthy subjects (age range, 12-78 yr). With progressing age, a significant but small increase in photopigment density difference (bleached versus dark adapted eye) and an increase in the time constant of rhodopsin regeneration was found. The increased density difference in rods was consistent with morphologic findings of increased rod outer segment diameter and disc content in older subjects. To explain this change in terms of the decreased specular reflections at the level of the inner limiting membrane was inadequate because age effects were independent of wavelength in the region of 450-550 nm. To control for the effects of ocular stray light from the lens, subjects older than 40 yr with a clear crystalline lens were measured and compared with those with pseudophakia. No statistically significant difference was found between the two groups. Increased rod density difference contrasts sharply with an earlier reported decrease in this parameter for foveal cones. The slowing of the regeneration rate is a phenomenon common to rods and cones. It may be a result of a gradual metabolic dysfunction of the retinal pigment epithelium in older subjects. Invest Ophthalmol Vis Sci 32:2676-2682, 1991 In 1722, Anthony van Leeuwenhoek (1632-1723) was probably the first to observe rod photoreceptor cells in the human retina by microscopy, 1 although he was undoubtedly unaware of their functional role. Although much knowledge has been gained on the physiology of vision by rods, age-related changes in rods in the living human eye with regard to their photopigment kinetics have not been documented to our knowledge. We investigated age effects of rod photopigment with the Utrecht fundus reflection densitometer (FC Donders Institute of Ophthalmology, Utrecht, The Netherlands), as a sequel to earlier studies on aging of human cone photopigment kinetics. In addition, the data may be used as a control group for further studies about age-related retinal diseases. Morphologically, rod photoreceptors undergo structural changes with age. A reduction in the number of photoreceptor nuclei (both rods and cones) was reported to be associated with aging, as was a displacement of these nuclei. 7 These authors found evidence for an age-related loss of RPE in both whites and blacks. In whites, photoreceptor loss was significantly and di- rectly correlated with lipofuscin concentration in the opposing RPE but was not related to age. In blacks, however, lipofuscin was not a strong determinant of photoreceptor loss. Detailed histologic information on the morphology of rod outer segments (ROS) was reported. 8 Early studies of aging and dark adaptation 9 " 13 showed a significant decrease in absolute sensitivity with age, but recently insignificant changes in rod sensitivity with age were reported in a study that carefully controlled for preretinal changes. 14 Several investigators 15 " 17 studied age effects to flash stimulation with electroretinography in healthy subjects. They found no significant age correlation for scotopic a-wave amplitude, but the b-wave decreased with age. In summary, histologic data indicate senile rod photoreceptor changes starting after age 40 yr and involving 10-20% of the total rod population, but functional tests show little or no impairment of responses of the photoreceptor ROS. Our densitometric data corroborate these findings. A statistically significant, but small, increase in both rod photopigment density and the time constant of regeneration was found throughout the second to eighth decade of life. Materials and Methods Subjects Healthy subjects (age range, 12-78 yr) participated in the study which was approved by the University Hospital ethics committee. Informed consent was obtained from all participants. All subjects underwent a routine ophthalmologic examination. Patient selection criteria were good physical and mental health, no Downloaded from iovs.arvojournals.org on 07/01/201

Heat shock protein expression in the eye and in uveal melanoma

PURPOSE: Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types, whereas HSPs may also have clinical use as stimulators in tumor vaccination. HSP expression levels were determined in normal eyes and in uveal melanoma and tested whether HSPs expression was associated with prognostic parameters in the uveal melanoma. METHODS: Expression of HSP27, HSP70, HSP90, and glycoprotein96 (GP96) were determined on paraffin-embedded and frozen sections from seven healthy eyes, 20 primary uveal melanomas without prior treatment, and 18 uveal melanomas after prior treatment. HSP expression was determined by alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemistry, using appropriate monoclonal antibodies and scored semiquantitatively. Expression of HSPs was validated on retinal tissue of a normal eye and in two uveal melanoma cell lines by Western blot analysis. RESULTS: Expression of HSPs was observed in epithelial and pigment cells of the normal eyes. In uveal melanoma, the level of expression of HSPs varied. Expression of HSP27 and GP96 was noted in more than 30 of 38 uveal melanomas (with, respectively, a mean of 66% and 53% positive cells). HSP70 and HSP90 were expressed in 6% of tumor cells. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors. There was not a significant difference in expression of the HSPs between uveal melanomas with or without any type of prior treatment. CONCLUSIONS: In this study, expression of HSPs in uveal melanoma is not correlated with known histopathologic prognostic factors. The high expression of GP96 indicates that this protein is a potential vector in tumor vaccination in patients with large uveal melanoma

Chronic central serous chorioretinopathy: long-term follow-up and vision-related quality of life

To describe the clinical findings and long-term outcome of patients with chronic central serous chorioretinopathy (cCSC). This was a retrospective case series in 52 eyes of 36 patients with a follow-up period of at least 1 year. Extensive ophthalmic examination and a validated questionnaire concerning vision-related quality of life (National Eye Institute Visual Function Questionnaire [NEI-VFQ]-39) were analyzed. Mean visual acuity showed a significant decline over time of 0.16 logarithm of minimum angle of resolution ([logMAR] range: -0.22 to 1.3; P=0.009) after a mean follow-up period of 10.6 years. Also, patients reported lower vision-related quality of life based on the NEI-VFQ-39 for almost all categories compared to healthy controls. Macular atrophy was diagnosed more often on optical coherence tomography compared to other diagnostic entities. Retinal pigment epithelium detachments in the macula were documented on optical coherence tomography in 56% of the patients. A significant thinning of foveal thickness was measured over time compared to unaffected fellow eyes (P=0.002). On long-term follow-up, 13 eyes (37%) showed an increase in number of hot spots on fluorescein angiography. This study indicates that cCSC is a progressive disease in many patients, causing a progressive decline in visual acuity, accompanied by lower reported vision-related quality of life. In deciding whether or not to treat, the progressive nature of cCSC should be taken into account in this relatively young and often still professionally active patient grou

Chronic central serous chorioretinopathy: long-term follow-up and vision-related quality of life

Purpose: To describe the clinical findings and long-term outcome of patients with chronic central serous chorioretinopathy (cCSC). Materials and methods: This was a retrospective case series in 52 eyes of 36 patients with a follow-up period of at least 1 year. Extensive ophthalmic examination and a validated questionnaire concerning vision-related quality of life (National Eye Institute Visual Function Questionnaire [NEI-VFQ]-39) were analyzed. Results: Mean visual acuity showed a significant decline over time of 0.16 logarithm of minimum angle of resolution ([logMAR] range: -0.22 to 1.3; P=0.009) after a mean follow-up period of 10.6 years. Also, patients reported lower vision-related quality of life based on the NEI-VFQ-39 for almost all categories compared to healthy controls. Macular atrophy was diagnosed more often on optical coherence tomography compared to other diagnostic entities. Retinal pigment epithelium detachments in the macula were documented on optical coherence tomography in 56% of the patients. A significant thinning of foveal thickness was measured over time compared to unaffected fellow eyes (P=0.002). On long-term follow-up, 13 eyes (37%) showed an increase in number of hot spots on fluorescein angiography. Conclusion: This study indicates that cCSC is a progressive disease in many patients, causing a progressive decline in visual acuity, accompanied by lower reported vision-related quality of life. In deciding whether or not to treat, the progressive nature of cCSC should be taken into account in this relatively young and often still professionally active patient group

A pilot study on slit lamp-adapted optical coherence tomography imaging of trabeculectomy filtering blebs.

Item does not contain fulltextBACKGROUND: Our study aims to identify anatomical characteristics of glaucoma filtering blebs by means of slit lamp-adapted optical coherence tomography (SL-OCT) and to identify new parameters for the functional prognosis of the filter in the early post-operative period. METHODS: Patients with primary open-angle glaucoma, aged 18 years and older, scheduled for primary trabeculectomy at the Department of Ophthalmology, Radboud University Nijmegen Medical Centre, were considered for our study. All patients underwent standardized trabeculectomy with intra-operative application of mitomycin C. The filtering blebs were evaluated clinically and with SL-OCT on day 1 and 1, 2, 4 and 12 weeks following surgery. The resulting data were analysed and weighed against surgical success. To better understand the SL-OCT data a small comparative histologic study was performed. RESULTS: The study included 20 eyes of 20 patients. After completion of our study, 15 eyes of 15 patients (mean age+/-SD 67 +/- 16 years) were eligible for data analysis and 5 eyes missed at least one follow-up visit. Filtering surgery was considered successful (intraocular pressure < or = 21 mmHg without antiglaucomatous medication) in 11 of 15 eyes. SL-OCT frequently demonstrated multiple hypo-reflective layers within Tenon's capsule ("striping" phenomenon) in the first post-operative week. Presumably, these layers corresponded with drainage channels in the histological specimen. These channels were present in functional filters but not in the failures. In addition, the visualisation of the sclera below the filtering zone was better defined in failures compared with successful filtering blebs ("shading" phenomenon). We observed no differences in the volume and clinical aspect of the blebs in the successful group compared with the unsuccessful group. CONCLUSIONS: Successful filtering blebs show characteristic optical properties on SL-OCT. These phenomena suggest a diffusely enhanced fluid content and the presence of intra-bleb drainage channels in functional filtering blebs