Multi-Modal retinal image analysis via deep learning for the diagnosis of intermediate dry age-related macular degeneration: a feasibility study

Background and Objective. To determine if using a multi-input deep learning approach in the image analysis of optical coherence tomography (OCT), OCT angiography (OCT-A), and colour fundus photographs increases the accuracy of a CNN to diagnose intermediate dry age-related macular degeneration (AMD). Patients and Methods. Seventy-five participants were recruited and divided into three cohorts: young healthy (YH), old healthy (OH), and patients with intermediate dry AMD. Colour fundus photography, OCT, and OCT-A scans were performed. The convolutional neural network (CNN) was trained on multiple image modalities at the same time. Results. The CNN trained using OCT alone showed a diagnostic accuracy of 94%, whilst the OCT-A trained CNN resulted in an accuracy of 91%. When multiple modalities were combined, the CNN accuracy increased to 96% in the AMD cohort. Conclusions. Here we demonstrate that superior diagnostic accuracy can be achieved when deep learning is combined with multimodal image analysis

The combination of intravitreal triamcinolone and phacoemulsification surgery in patients with diabeticfoveal oedema and cataract

BACKGROUND: The management of diabetic patients with refractory macular oedema or patients with no adequate pre-operative view to administer laser treatment provide a challenge to the ophthalmologist. We wished to assess the use, safety and effect of intravitreal triamcinolone injection at the time of cataract surgery in patients with diabetic foveal oedema and sight limiting lens opacities. METHOD: This was a longitudinal non-randomised prospective pilot study in 18 eyes (12 patients). All patients had visually significant lens opacities and either persistent diabetic foveal oedema unresponsive to laser treatment-group A, or foveal oedema with no adequate pre-operative view for laser treatment- group B. The cataract surgery was carried out under full aseptic technique using a self-sealing temporal incision and a foldable acrylic lens. Intravitreal triamcinolone was given infratemporally pars plana at the completion of the cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months and then every 3 months as required. The Wilcoxin matched-pairs test was used to assess the significance of the improvement in visual acuity at 2 months. RESULTS: Twelve patients with a total of 18 eyes were included in the study. There were 10 patients (15 eyes) in group A and 3 patients (3 eyes) in group B. Preoperatively 16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at two months review ranged from 6/6 to CF with 9 eyes (50%) achieving 6/12 or better (7 eyes (47%) in group A and 2 eyes (67%) in group B). Three eyes had no recorded improvement in visual acuity, but no eyes had deterioration in acuity. The improvement in visual acuity was significant at p = 0.001. There were no significant sight threatening complications. CONCLUSION: Intravitreal triamcinolone has been shown to lead to an improvement in macular oedema and visual improvement in diabetic patients not undergoing cataract surgery but has not, to our knowledge, been previously used in a study like this one. We suggest that intravitreal injection at the time of cataract surgery could be carried out safely with encouraging visual outcomes in patients with diabetic foveal oedema and cataract

Collagen reorganization at the tumor-stromal interface facilitates local invasion

BACKGROUND: Stromal-epithelial interactions are of particular significance in breast tissue as misregulation of these interactions can promote tumorigenesis and invasion. Moreover, collagen-dense breast tissue increases the risk of breast carcinoma, although the relationship between collagen density and tumorigenesis is not well understood. As little is known about epithelial-stromal interactions in vivo, it is necessary to visualize the stroma surrounding normal epithelium and mammary tumors in intact tissues to better understand how matrix organization, density, and composition affect tumor formation and progression. METHODS: Epithelial-stromal interactions in normal mammary glands, mammary tumors, and tumor explants in three-dimensional culture were studied with histology, electron microscopy, and nonlinear optical imaging methodologies. Imaging of the tumor-stromal interface in live tumor tissue ex vivo was performed with multiphoton laser-scanning microscopy (MPLSM) to generate multiphoton excitation (MPE) of endogenous fluorophores and second harmonic generation (SHG) to image stromal collagen. RESULTS: We used both laser-scanning multiphoton and second harmonic generation microscopy to determine the organization of specific collagen structures around ducts and tumors in intact, unfixed and unsectioned mammary glands. Local alterations in collagen density were clearly seen, allowing us to obtain three-dimensional information regarding the organization of the mammary stroma, such as radiating collagen fibers that could not have been obtained using classical histological techniques. Moreover, we observed and defined three tumor-associated collagen signatures (TACS) that provide novel markers to locate and characterize tumors. In particular, local cell invasion was found predominantly to be oriented along certain aligned collagen fibers, suggesting that radial alignment of collagen fibers relative to tumors facilitates invasion. Consistent with this observation, primary tumor explants cultured in a randomly organized collagen matrix realigned the collagen fibers, allowing individual tumor cells to migrate out along radially aligned fibers. CONCLUSION: The presentation of these tumor-associated collagen signatures allowed us to identify pre-palpable tumors and see cells at the tumor-stromal boundary invading into the stroma along radially aligned collagen fibers. As such, TACS should provide indications that a tumor is, or could become, invasive, and may serve as part of a strategy to help identify and characterize breast tumors in animal and human tissues

Essentials of a robust deep learning system for diabetic retinopathy screening: A systematic literature review

This systematic review was performed to identify the specifics of an optimal diabetic retinopathy deep learning algorithm, by identifying the best exemplar research studies of the field, whilst highlighting potential barriers to clinical implementation of such an algorithm. Searching five electronic databases (Embase, MEDLINE, Scopus, PubMed, and the Cochrane Library) returned 747 unique records on 20 December 2019. Predetermined inclusion and exclusion criteria were applied to the search results, resulting in 15 highest-quality publications. A manual search through the reference lists of relevant review articles found from the database search was conducted, yielding no additional records. A validation dataset of the trained deep learning algorithms was used for creating a set of optimal properties for an ideal diabetic retinopathy classification algorithm. Potential limitations to the clinical implementation of such systems were identified as lack of generalizability, limited screening scope, and data sovereignty issues. It is concluded that deep learning algorithms in the context of diabetic retinopathy screening have reported impressive results. Despite this, the potential sources of limitations in such systems must be evaluated carefully. An ideal deep learning algorithm should be clinic-, clinician-, and camera-agnostic; complying with the local regulation for data sovereignty, storage, privacy, and reporting; whilst requiring minimum human input

Bevacizumab for diabetic macular oedema: one-year treatment outcomes from the Fight Retinal Blindness! Registry

OBJECTIVES This study evaluated the 1-year treatment outcomes of bevacizumab for diabetic macular oedema (DMO) in routine clinical practice. METHODS A retrospective analysis was performed on 298 eyes of 220 patients with DMO that received intra-vitreal bevacizumab between 1 September 2013 and 31 August 2018 that were tracked by a prospectively designed, web-based observational registry-the Fight Retinal Blindness! Registry. RESULTS The mean visual acuity (95% confidence interval [CI]) at 1-year was 3 (2, 5) letters better than a mean (SD) of 68 (15) letters at study entry. Nearly a quarter of eyes achieved ≥20/40. Eyes presenting with better vision (≥20/40) tended to maintain that vision during the period of observation, whereas those presenting with worse vision (<20/40) gained a mean (95% CI) of 9 (5, 13) letters. A mean reduction in the macular thickness was observed over the study period with the central subfield improving by 29 µm (95% CI 17, 40) from a mean (SD) of 402 (109) µm at study entry. Eyes that completed 1 year of follow-up received a median (Q1, Q3) of 7 (4, 9) bevacizumab injections. Sixty-two eyes, ~20%, that started with bevacizumab changed to either another VEGF inhibitor or steroid (triamcinolone) during the period of observation. This did not lead to functional improvement for eyes changed to either ranibizumab or aflibercept despite a further reduction in macular thickness. An improvement in vision and reduction in macular thickness was noted in the 13 eyes that subsequently received triamcinolone. Approximately 10% of eyes dropped out over 12 months, even though their mean visual acuity had improved by seven letters from the initial visit. CONCLUSIONS Bevacizumab is an effective treatment for DMO in unselected populations

A Multicountry Comparison of Real-World Management and Outcomes of Polypoidal Choroidal Vasculopathy: Fight Retinal Blindness! Cohort

PURPOSE To compare the 12-month real-world visual and disease activity outcomes of eyes with polypoidal choroidal vasculopathy (PCV) treated with a combination of photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) injections (combination group) versus those eyes treated with anti-VEGF monotherapy alone with rescue PDT being used as required (monotherapy group). DESIGN Database comparative observational study. PARTICIPANTS Eyes with PCV as graded in the Fight Retinal Blindness! database from Australia, New Zealand, Singapore, and Switzerland. METHODS Clinical information from a multisite, international registry of neovascular age-related macular degeneration was analyzed with an intention-to-treat approach. MAIN OUTCOME MEASURES Primary outcome measure was the change in visual acuity in logMAR letters over 12 months between the two groups analyzed with intention-to-treat approach. RESULTS Forty-one and 152 eyes received combination therapy and anti-VEGF monotherapy, respectively. All anti-VEGF agents were pooled, and bevacizumab represented 66.1% of injections administered. The adjusted mean change in visual acuity between the combination group and monotherapy group at 12 months was +16.9 letters (95% confidence interval [CI], 10.6-23.3 letters) and +8.2 letters (95% CI, 5.2-11.3 letters), respectively (P = 0.02). Proportion of inactive lesions and mean time to inactivity was 85.3% and 80.7 days (95% CI, 62.8-98.5 days), respectively, in the combination group compared with 76.8% and 150.4 days (95% CI, 132.8-168.0 days), respectively, in the monotherapy group (P = 0.01). The mean number of injections of anti-VEGF agent between the combination and monotherapy groups was 4.3 injections (95% CI, 3.6-5.2 injections) and 6.4 injections (95% CI, 5.9-6.9 injections), respectively (P = 0.01). CONCLUSIONS The real-world outcomes for treatment of PCV showed larger gains in vision, higher proportion of inactive lesions, quicker time to inactivity, and fewer injections administered in the combination group compared with the monotherapy group. These findings are consistent with current evidence reporting the advantages of combination therapy for PCV

Intravitreal pro-inflammatory cytokines in non-obese diabetic mice: Modelling signs of diabetic retinopathy.

Diabetic retinopathy is a vascular disease of the retina characterised by hyperglycaemic and inflammatory processes. Most animal models of diabetic retinopathy are hyperglycaemia-only models that do not account for the significant role that inflammation plays in the development of the disease. In the present study, we present data on the establishment of a new animal model of diabetic retinopathy that incorporates both hyperglycaemia and inflammation. We hypothesized that inflammation may trigger and worsen the development of diabetic retinopathy in a hyperglycaemic environment. Pro-inflammatory cytokines, IL-1β and TNF-α, were therefore injected into the vitreous of non-obese diabetic (NOD) mice. CD1 mice were used as same genetic background controls. Fundus and optical coherence tomography images were obtained before (day 0) as well as on days 2 and 7 after intravitreal cytokine injection to assess vessel dilation and beading, retinal and vitreous hyper-reflective foci and retinal thickness. Astrogliosis and microgliosis were assessed using immunohistochemistry. Results showed that intravitreal cytokines induced vessel dilation, beading, severe vitreous hyper-reflective foci, retinal oedema, increased astrogliosis and microglia upregulation in diabetic NOD mice. Intravitreal injection of inflammatory cytokines into the eyes of diabetic mice therefore appears to provide a new model of diabetic retinopathy that could be used for the study of disease progression and treatment strategies

'Miss, you're so gay.' Queer stories from trainee teachers

This is a postprint of an article whose final and definitive form has been published in Sex Education© 2004 Copyright Taylor & Francis; Sex Education is available online at http://www.informaworld.comThis study focuses on interviews with six lesbian, gay or bisexual trainee teachers, and explores their experiences in relation to sexual orientation. Initial analysis reveals interesting perspectives on the lives of trainees in Higher Education, during school-based work and socially; it also provides a window onto the attitudes to sexuality (individual and institutional) encountered by interviewees. Further analysis takes theoretical tools from three overlapping discourses in which these trainees are participants: the local campus culture, the construction of sexualities in schools, and wider society's perceptions of gender and sexuality. These tools uncover significant concerns around identity management, vulnerability and powerlessness, institutional silence, and the hegemonic masculinity of some student cultures. They also reveal significant creative resistance to discrimination, enabling us to conclude that, in spite of some methodological difficulties, idealism is not misplaced as an inspiration to emancipatory endeavour