Retrospective Evaluation of Melphalan, Vincristine, and Cytarabine Chemotherapy for the Treatment of Relapsed Canine Lymphoma.

Dogs diagnosed with multicentric lymphoma often relapse following induction therapy within the first year of treatment. The primary aim of this study was to evaluate the tolerability of a novel drug combination using melphalan, vincristine, and cytarabine (MOC) for the treatment of relapsed lymphoma. On day 1, dogs were treated with vincristine (0.5-0.6 mg/m2 IV) and cytarabine (300 mg/m2 IV over 4-6 hr or subcutaneously over 2 days). On day 7, dogs were treated with melphalan (20 mg/m2per os). This 2 wk protocol was repeated for at least three cycles or until treatment failure. Twenty-six dogs were treated with MOC and met the inclusion criteria. Twenty-three dogs had toxicity data, and all experienced adverse events with the majority graded as mild. The overall response rate was 38%, which included 19% of dogs who achieved a complete response. The median progression-free survival was 29 days (range 1-280 days). The overall clinical benefit was 65% for a median of 37 days (range 33-280 days). MOC is a safe treatment option for relapsed lymphoma in dogs.

Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis.

Background: Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line). Objectives: The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months). Search methods: We searched various electronic databases on 8 July 2022. Selection criteria: We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO. Data collection and analysis: We used standard Cochrane methods for pairwise meta-analysis and we augmented this evidence using network meta-analysis (NMA) methods. We used the Stata 'network' meta-analysis package for all analyses. We used the CINeMA (Confidence in Network Meta-Analysis) web application to grade the certainty of the evidence. Main results: We included 23 studies (13 with industry funding) that enrolled 3513 people with DMO (median central retinal thickness (CRT) 460 microns, interquartile range (IQR) 424 to 482) and moderate vision loss (median best-corrected visual acuity (BCVA) 0.48 logMAR, IQR 0.42 to 0.55. One study that investigated ranibizumab versus sham and one study that mainly enrolled people with subclinical DMO and normal BCVA were not suitable for inclusion in the efficacy NMA. Consistent with the previous update of this review, we used ranibizumab as the reference drug for efficacy, and control (including laser, observation, and sham) as the reference for systemic safety. Eight trials provided data on the primary outcome (change in BCVA at 24 months, in logMAR: lower is better). We found no evidence of a difference between the following interventions and ranibizumab alone: aflibercept (mean difference (MD) -0.05 logMAR, 95% confidence interval (CI) -0.12 to 0.02; moderate certainty); bevacizumab (MD -0.01 logMAR, 95% CI -0.13 to 0.10; low certainty), brolucizumab (MD 0.00 logMAR, 95% CI -0.08 to 0.07; low certainty), ranibizumab plus deferred laser (MD 0.00 logMAR, 95% CI -0.11 to 0.10; low certainty), and ranibizumab plus prompt laser (MD 0.03 logMAR, 95% CI -0.04 to 0.09; very low certainty). We also analysed BCVA change at 12 months, finding moderate-certainty evidence of increased efficacy with brolucizumab (MD -0.07 logMAR, 95%CI -0.10 to -0.03 logMAR), faricimab (MD -0.08 logMAR, 95% CI -0.12 to -0.05), and aflibercept (MD -0.07 logMAR, 95 % CI -0.10 to -0.04) compared to ranibizumab alone, but the difference could be clinically insignificant. Compared to ranibizumab alone, NMA of six trials showed no evidence of a difference with aflibercept (moderate certainty), bevacizumab (low certainty), or ranibizumab with prompt (very low certainty) or deferred laser (low certainty) regarding improvement by three or more ETDRS lines at 24 months. There was moderate-certainty evidence of greater CRT reduction at 24 months with brolucizumab (MD -23 microns, 95% CI -65 to -1 9) and aflibercept (MD -26 microns, 95% CI -53 to 0.9) compared to ranibizumab. There was moderate-certainty evidence of lesser CRT reduction with bevacizumab (MD 28 microns, 95% CI 0 to 56), ranibizumab plus deferred laser (MD 63 microns, 95% CI 18 to 109), and ranibizumab plus prompt laser (MD 72 microns, 95% CI 25 to 119) compared with ranibizumab alone. Regarding all-cause mortality at the longest available follow-up (20 trials), we found no evidence of increased risk of death for any drug compared to control, although effects were in the direction of an increase, and clinically relevant increases could not be ruled out. The certainty of this evidence was low for bevacizumab (risk ratio (RR) 2.10, 95% CI 0.75 to 5.88), brolucizumab (RR 2.92, 95% CI 0.68 to 12.58), faricimab (RR 1.91, 95% CI 0.45 to 8.00), ranibizumab (RR 1.26, 95% CI 0.68 to 2.34), and very low for conbercept (RR 0.33, 95% CI 0.01 to 8.81) and aflibercept (RR 1.48, 95% CI 0.79 to 2.77). Estimates for Antiplatelet Trialists Collaboration arterial thromboembolic events at 24 months did not suggest an increase with any drug compared to control, but the NMA was overall incoherent and the evidence was of low or very low certainty. Ocular adverse events were rare and poorly reported and could not be assessed in NMAs. Authors' conclusions: There is limited evidence of the comparative efficacy and safety of anti-VEGF drugs beyond one year of follow-up. We found no clinically important differences in visual outcomes at 24 months in people with DMO, although there were differences in CRT change. We found no evidence that any drug increases all-cause mortality compared to control, but estimates were very imprecise. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated, and the individuals exposed to these drugs may be less healthy than trial participants.

A randomised controlled trial evaluating internal limiting membrane peeling forceps in macular hole surgery.

PURPOSE: To assess study design and a range of anatomical and functional changes after internal limiting membrane (ILM) peeling using forceps developed for atraumatic ILM pick-up compared to standard forceps. METHODS: We conducted a masked proof-of concept randomised controlled trial (RCT) on 65 patients who underwent ILM peeling for idiopathic full-thickness macular hole (FTMH) using etched-tip forceps (etched-tip group, 33 eyes) compared to standard ILM forceps (smooth-tip group, 32 eyes). Patients were assessed preoperatively, 3 weeks, 3 and 6 months postoperatively. RESULTS: The primary closure rate was 95.4%. There was no statistically significant difference between the groups in terms of final visual acuity (66.9 vs 70.9 ETDRS letters, p = 0.13), difference of visual field mean deviation (1.32 vs 1.14 decibels), and number of eyes with pick-up-related retinal haemorrhages (16% vs 16%, p = 0.96), swelling of arcuate nerve fibre layer lesions (63% vs 55%, p = 0.54), number of dissociated optic nerve fibre layer lesions (31.4 vs 41.0, p = 0.16), nor inner retina defects (37% vs 22%, p = 0.17). Similar changes in inner retinal volumes were detected in all 9 sectors of an ETDRS grid except for a trend (p = 0.06) towards a lower reduction in the inferior inner sector in the etched-tip group. CONCLUSIONS: The study was successfully completed with masking maintained and a low risk of bias. Multiple endpoints relating to ILM peeling were assessed, and estimates were provided that can be used for future studies. Although the study was not powered to assess any specific endpoint, the anatomical and functional outcomes assessed did not significantly differ.

Inclusion of diabetic retinopathy screening strategies in national-level diabetes care planning in low- and middle-income countries: a scoping review.

BACKGROUND: Diabetes is a major public health concern, with approximately 80% of the burden falling on low- and middle-income countries (LMICs). Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and early detection through diabetic eye screening programmes is essential to prevent visual impairment and blindness. Careful planning at a national level is crucial for effective implementation of such programmes. METHODS: A scoping review was conducted, and the protocol was published previously to explain the methods in detail. Data were collected from databases and searches, including grey literature. Furthermore, consultations were conducted with key informants from LMICs. RESULTS: Lower-middle-income countries (29/50, 58%) and upper-middle-income countries (27/59, 45.8%) are making more progress than low-income countries (4/29, 13.8%) in terms of DR policy planning. However, no identified data for published policies have actually implemented national DR policies. Compared to low-income and lower-middle-income countries, upper-middle-income countries are making the most progress in implementing national diabetic eye screening programmes; however, their progress is still slow, with only 5/59 (8.5%) having such programmes. CONCLUSION: There are significant gaps in the literature, with no data reported for 78/138 (56.5%) LMICs. Further research is clearly needed to support and document DR policy development in LMICs.

Shaved margin histopathology and imprint cytology for assessment of excision in canine mast cell tumors and soft tissue sarcomas.

OBJECTIVE: To determine the feasibility and agreement of margin assessment by imprint cytology, shaved margin histopathology, and radial section histopathology in canine cutaneous and subcutaneous mast cell tumors (MCT) and soft tissue sarcomas (STS). STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Three hundred and forty margins from 72 excised tumors (52 MCT and 20 STS) in 54 client-owned dogs. METHODS: Imprint cytology samples were acquired by pressing glass slides to the cut surgical margin of the freshly excised surgical specimen. Shaved margin samples were obtained from the patient wound bed using a scalpel immediately prior to closure. Radial section histopathology was performed as part of routine histopathologic processing. All margins were assessed as either positive or negative for presence of tumor cells at the surgical margin. Agreement among methods was calculated using Fleiss Kappa coefficients and an association of method, margin direction, and tumor type with positive margin status was evaluated using a general linear mixed model. RESULTS: Positive margin detection rates differed for MCT (imprint cytology 21%, radial section histopathology 9%, and shaved margin histopathology 3%; P < .0001) but not for STS. Intermethod agreement was poor (Fleiss Kappa = 0.051 and 0.176 for MCT and STS, respectively). Margin direction did not influence margin status for either tumor type. CONCLUSION: Imprint cytology and shaved margin histopathology are feasible, but their results are frequently disparate from routine radial section histopathology. Future studies are needed to evaluate the correlation of each method with local recurrence rates.

Prevalence and Predictors of Diabetic Retinopathy, Its Progression and Regression in Indian Children and Youth With Type-1 Diabetes.

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P < .05). Subjects with DR had significantly higher triglyceride concentrations (P < .05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P < .05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D.

Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D.

Reproducibility of SIMPLE classification for diabetic retinopathy screening and its comparison to current Italian guidelines.

PURPOSE: To evaluate the reproducibility of SIMPLE (Single field Image Multi Parameters defined Lesions Extent), a new Diabetic Retinopathy (DR) classification for screening of 45° single field fundus pictures of patients with diabetes (PwDM), assessing DR, Diabetic Maculopathy (DMac) and referral rate agreement and comparing it to current Italian Guidelines (IG). MATERIALS AND METHODS: We conducted a retrospective, observational, multicentre study, collecting 1000 retinal 45° single field images of PwDM obtained during routine visits in two diabetes clinics. Three ophthalmologists evaluated each image, determining the presence and number of specific DR lesions and then assigning a stage according to the current IG for screening. SIMPLE staging was performed automatically via Excel software, based on the pre-specified DR characteristics observed by the graders. We analysed intra-centre, inter-centre and total inter-grader agreement for DR and DMac stage and referral rate of the two classifications. RESULTS: Agreement amongst the three graders was consistently higher when using SIMPLE classification than when using current IG classification. For DR, kappa (k) was 0.86 with IG and 0.95 with SIMPLE classification; for DMac, k-IG was 0.78, while k-SIMPLE was 0.96; concordance on the referral rate was 0.91 with IG and 0.99 with SIMPLE. Similar results were obtained in sub-analyses for the evaluation of intra-centre and inter-centre concordance. CONCLUSIONS: Our results suggest that the new SIMPLE classification has an excellent reproducibility amongst graders, comparable or superior to the current IG for DR screening proposed in 2015, improving the standardisation of the decision on referability.

Automated Machine Learning for Predicting Diabetic Retinopathy Progression From Ultra-Widefield Retinal Images.

Importance: Machine learning (ML) algorithms have the potential to identify eyes with early diabetic retinopathy (DR) at increased risk for disease progression. Objective: To create and validate automated ML models (autoML) for DR progression from ultra-widefield (UWF) retinal images. Design, Setting and Participants: Deidentified UWF images with mild or moderate nonproliferative DR (NPDR) with 3 years of longitudinal follow-up retinal imaging or evidence of progression within 3 years were used to develop automated ML models for predicting DR progression in UWF images. All images were collected from a tertiary diabetes-specific medical center retinal image dataset. Data were collected from July to September 2022. Exposure: Automated ML models were generated from baseline on-axis 200° UWF retinal images. Baseline retinal images were labeled for progression based on centralized reading center evaluation of baseline and follow-up images according to the clinical Early Treatment Diabetic Retinopathy Study severity scale. Images for model development were split 8-1-1 for training, optimization, and testing to detect 1 or more steps of DR progression. Validation was performed using a 328-image set from the same patient population not used in model development. Main Outcomes and Measures: Area under the precision-recall curve (AUPRC), sensitivity, specificity, and accuracy. Results: A total of 1179 deidentified UWF images with mild (380 [32.2%]) or moderate (799 [67.8%]) NPDR were included. DR progression was present in half of the training set (590 of 1179 [50.0%]). The model's AUPRC was 0.717 for baseline mild NPDR and 0.863 for moderate NPDR. On the validation set for eyes with mild NPDR, sensitivity was 0.72 (95% CI, 0.57-0.83), specificity was 0.63 (95% CI, 0.57-0.69), prevalence was 0.15 (95% CI, 0.12-0.20), and accuracy was 64.3%; for eyes with moderate NPDR, sensitivity was 0.80 (95% CI, 0.70-0.87), specificity was 0.72 (95% CI, 0.66-0.76), prevalence was 0.22 (95% CI, 0.19-0.27), and accuracy was 73.8%. In the validation set, 6 of 9 eyes (75%) with mild NPDR and 35 of 41 eyes (85%) with moderate NPDR progressed 2 steps or more were identified. All 4 eyes with mild NPDR that progressed within 6 months and 1 year were identified, and 8 of 9 (89%) and 17 of 20 (85%) with moderate NPDR that progressed within 6 months and 1 year, respectively, were identified. Conclusions and Relevance: This study demonstrates the accuracy and feasibility of automated ML models for identifying DR progression developed using UWF images, especially for prediction of 2-step or greater DR progression within 1 year. Potentially, the use of ML algorithms may refine the risk of disease progression and identify those at highest short-term risk, thus reducing costs and improving vision-related outcomes.

A biomechanical study of laparoscopic 4S-modified Roeder and Weston knot strength in 3-0 polyglactin 910 and 3-0 polydioxanone.

OBJECTIVE: To (1) evaluate biomechanical strength of 4 different laparoscopic knots using 2 suture types, and (2) evaluate carotid artery ligature bursting pressure of 2 knots using a single suture type. STUDY DESIGN: Biomechanical materials testing. SAMPLE POPULATION: Suture material (3-0 polydioxanone, 3-0 polyglactin 910). METHODS: Four knot types were tested: 4S-modified Roeder (4SMR) Weston plus 3 square throws (W3S); Weston plus 3 granny throws (W3G); and a 4 square throw knot as a control (control); 24 specimens of each knot type were tied with 3-0 polyglactin 910 and 24 of 3 knot types (4SMR, W3S, control) were tied with 3-0 polydioxanone. Suture loop constructs were tested to 3 mm displacement failure and ultimate failure. Carotid artery ligation bursting pressure was tested using 10 samples each of 4SMR and W3S knots with 3-0 polyglactin 910. RESULTS: The W3S, W3G, and controls were similar. The 4SMR was similar to W3S using 3-0 PDS but the 4SMR had lower load to failure and greater elongation than the Weston using 3-0 polyglactin 910. The 4SMR had a higher slippage rate with 3-0 polyglactin 910. All ligatures withstood supraphysiologic pressures. CONCLUSIONS: Surgeons using 3-0 polyglactin 910 should consider using the Weston knot with added throws during laparoscopic procedures.

CHILDSTAR: CHIldren Living With Diabetes See and Thrive with AI Review.

Background: Artificial intelligence (AI) appears capable of detecting diabetic retinopathy (DR) with a high degree of accuracy in adults; however, there are few studies in children and young adults. Methods: Children and young adults (3-26 years) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) were screened at the Dhaka BIRDEM-2 hospital, Bangladesh. All gradable fundus images were uploaded to Cybersight AI for interpretation. Two main outcomes were considered at a patient level: 1) Any DR, defined as mild non-proliferative diabetic retinopathy (NPDR or more severe; and 2) Referable DR, defined as moderate NPDR or more severe. Diagnostic test performance comparing Orbis International's Cybersight AI with the reference standard, a fully qualified optometrist certified in DR grading, was assessed using the Matthews correlation coefficient (MCC), area under the receiver operating characteristic curve (AUC-ROC), area under the precision-recall curve (AUC-PR), sensitivity, specificity, positive and negative predictive values. Results: Among 1274 participants (53.1% female, mean age 16.7 years), 19.4% (n = 247) had any DR according to AI. For referable DR, 2.35% (n = 30) were detected by AI. The sensitivity and specificity of AI for any DR were 75.5% (CI 69.7-81.3%) and 91.8% (CI 90.2-93.5%) respectively, and for referable DR, these values were 84.2% (CI 67.8-100%) and 98.9% (CI 98.3%-99.5%). The MCC, AUC-ROC and the AUC-PR for referable DR were 63.4, 91.2 and 76.2% respectively. AI was most successful in accurately classifying younger children with shorter duration of diabetes. Conclusions: Cybersight AI accurately detected any DR and referable DR among children and young adults, despite its algorithms having been trained on adults. The observed high specificity is particularly important to avoid over-referral in low-resource settings. AI may be an effective tool to reduce demands on scarce physician resources for the care of children with diabetes in low-resource settings.

UK Biobank retinal imaging grading: methodology, baseline characteristics and findings for common ocular diseases.

BACKGROUND/OBJECTIVES: This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009-2010, and to characterise individuals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy. METHODS: Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD; either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features; photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms; either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements. RESULTS: Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension. CONCLUSIONS: This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health.

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden.

Importance: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. Objective: To evaluate phenotypic features across genetic burden for POAG. Design, Setting, and Participants: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. Main Outcomes and Measures: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. Results: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 µm and macular ganglion cell complex (GCC) of 0.26 µm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). Conclusion and Relevance: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.

Navigating the Unseen City: Town Planners, Architects, Ophthalmic Professionals, and Charity Opinions on Navigating of the Built Environment with a Visual Impairment.

People with a visual impairment often find navigating around towns and cities difficult. Streetscape features such as bollards, street cafés, and parked cars on pavements are some of the most common issues. in this paper semi-structured interviews were conducted with stakeholders including built environment professionals, visually impaired individuals, ophthalmic professionals, and sight loss charities. All stakeholders felt there were barriers and enablers to navigating streets with a visual impairment. Stakeholders agreed these can have an impact on the daily lives of those with a visual impairment. While built environment professionals knew of policies and guidance around accessibility for people with a visual impairment, there was a lack of professional knowledge about the spectrum of visual impairment. Despite this, stakeholders felt these small changes could have a positive impact, making accessible cities for all. A collaborative approach to streetscape design and further education could help create better environments for all.

Impact of targeted diabetic retinopathy training for graders in Vietnam and the implications for future diabetic retinopathy screening programmes: a diagnostic test accuracy study.

OBJECTIVES: To compare the accuracy of trained level 1 diabetic retinopathy (DR) graders (nurses, endocrinologists and one general practitioner), level 2 graders (midlevel ophthalmologists) and level 3 graders (senior ophthalmologists) in Vietnam against a reference standard from the UK and assess the impact of supplementary targeted grader training. DESIGN: Diagnostic test accuracy study. SETTING: Secondary care hospitals in Southern Vietnam. PARTICIPANTS: DR training was delivered to Vietnamese graders in February 2018 by National Health Service (NHS) UK graders. Two-field retinal images (412 patient images) were graded by 14 trained graders in Vietnam between August and October 2018 and then regraded retrospectively by an NHS-certified reference standard UK optometrist (phase I). Further DR training based on phase I results was delivered to graders in November 2019. After training, a randomised subset of images from January to October 2020 (115 patient images) was graded by six of the original cohort (phase II). The reference grader regraded all images from phase I and II retrospectively in masked fashion. PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity was calculated at the two different time points, and χ2 was used to test significance. RESULTS: In phase I, the sensitivity for detecting any DR for all grader groups in Vietnam was low (41.8-42.2%) and improved in phase II after additional training was delivered (51.3-87.2%). The greatest improvement was seen among level 1 graders (p<0.001), and the lowest improvement was observed among level 3 graders (p=0.326). There was a statistically significant improvement in sensitivity for detecting referable DR and referable diabetic macular oedema between all grader levels. The post-training values ranged from 40.0 to 61.5% (including ungradable images) and 55.6%-90.0% (excluding ungradable images). CONCLUSIONS: This study demonstrates that targeted training interventions can improve accuracy of DR grading. These findings have important implications for improving service delivery in DR screening programmes in low-resource settings.

Ophthalmologists' and patients' perspectives on treatments for diabetic retinopathy and maculopathy in Vietnam: a descriptive qualitative study.

INTRODUCTION: Globally, diabetic retinopathy (DR) is the leading cause of blindness in working-aged adults. Early detection and treatment of DR is essential for preventing sight loss. Services must be available, accessible and acceptable to patients if we are to ensure they seek such care. OBJECTIVES: To understand patients' knowledge and attitudes towards laser versus antivascular endothelial growth factor (VEGF) injections to treat DR in Vietnam, and to identify factors Vietnamese ophthalmologists consider when making treatment decisions. METHODS: This is a descriptive qualitative study based on semi-structured interviews with 18 patients (12 from Ho Chi Minh City and 6 from Hanoi) plus individual interviews with 24 ophthalmologists working in eye clinics in these cities. Thematic analysis was used to analyse the data. RESULTS: In total, 10/24 (41.7%) ophthalmologists were female, and their median age was 41 years (range 29-69 years). The median age of patients was 56.5 years (range 28-72 years), and 7/18 (38.9%) were female. Briefly, factors that influence DR treatment decisions for ophthalmologists are medical considerations (ie, severity of disease, benefits and risks), availability (ie, treatment and resources) and patient-related factors (ie, costs and adherence). Patient's perceived barriers and facilitators to treatments were based on patient and family related factors (ie, treatment and transportation costs) and previous treatment experiences (ie, positive and negative). Recommendations by all participants included ensuring that both laser and anti-VEGF injections are widely available across the country and controlling costs for patients and the healthcare system. CONCLUSIONS: Reducing DR treatment costs, optimising treatments options, and expanding the network of clinics offering treatment outside metropolitan areas were the main issues raised by participants. These findings can help inform policy changes in Vietnam and may be generalisable to other low-resource settings.

Capturing the clinical decision-making processes of expert and novice diabetic retinal graders using a 'think-aloud' approach.

BACKGROUND: Diabetic eye screening programmes have been developed worldwide based on evidence that early detection and treatment of diabetic retinopathy are crucial to preventing sight loss. However, little is known about the decision-making processes and training needs of diabetic retinal graders, particularly in low- and middle-income countries. OBJECTIVES: To provide data for improving evidence-based diabetic retinopathy training to help novice graders process fundus images more like experts. SUBJECTS/METHODS: This is a mixed-methods qualitative study conducted in southern Vietnam and Northern Ireland. Novice diabetic retinal graders in Vietnam (n = 18) and expert graders in Northern Ireland (n = 5) were selected through a purposive sampling technique. Data were collected from 21st February to 3rd September 2019. The interviewer used neutral prompts during think-aloud sessions to encourage participants to verbalise their thought processes while grading fundus images from anonymised patients, followed by semi-structured interviews. Thematic framework analysis was used to identify themes, supported by illustrative quotes from interviews. Mann-Whitney U tests were used to compare graders' performance. RESULTS: Expert graders used a more systematic approach when grading images, considered all four images per patient and used available software tools such as red-free filters prior to making a decision on management. The most challenging features for novice graders were intra-retinal microvascular abnormalities and new vessels, which were more accurately identified by experts. CONCLUSION: Taking more time to grade fundus images and adopting a protocol-driven "checklist" approach may help novice graders to function more like experts.

An Analysis of the Infections and Determination of Empiric Antibiotic Therapy in Cats and Dogs with Cancer-Associated Infections.

Cancer patients commonly develop infectious complications over the course of the disease. One thousand patients receiving treatment for an oncologic disease at a single veterinary teaching hospital were retrospectively reviewed for concurrent infections. A total of 153 confirmed bacterial infections were identified, 82 of which were abscesses or wounds, 13 of which were respiratory infections, 3 of which were ear infections, and 55 of which were urinary tract infections. It was observed that the majority of the infections were caused by bacteria that are normally associated with that specific site location. Escherichia coli was the most common pathogen linked to infections in general, but Staphylococcus pseudintermedius was a frequently identified pathogen associated with wound infections. The susceptibility to diverse antimicrobials varied with the site of infection. Eleven cases (7.1%) were caused by opportunistic infections of the site, and E. coli and Pseudomonas aeruginosa were the pathogens isolated. Those bacteria were resistant to many antibiotics but showed susceptibility to aminoglycosides, imipenem, quinolones, and polymyxin B. In conclusion, veterinary patients with cancer or those under treatment for tumors develop infections by commonly encountered bacteria in the different sites of the body, with a susceptibility to antibiotics that is not out of line from what is expected. A small subset of cases developed opportunistic infections, with microbes that were more resistant to many classes of antibiotics.

Inclusion of diabetic retinopathy screening strategies in national-level diabetes care planning in low-income and middle-income settings: protocol for a scoping review.

INTRODUCTION: The diabetes mellitus (DM) epidemic is a major public health concern globally, with the highest-burden in low-income and middle-income countries (LMICs). Diabetic retinopathy (DR) is a microvascular complication of diabetes, and if left untreated can lead to visual impairment and blindness. Epidemiological studies suggest that the incidence of sight-threatening DR is decreasing in high-income countries due to improved treatments and management of DM; however, these trends are not replicated in LMICs. In this paper, we outline a scoping review protocol that aims to identify which LMICs have included DR in their national DM, non-communicable disease or prevention of blindness plans. The scoping review also aims to assess gaps when implementing national DR screening programmes in LMICs. METHODS AND ANALYSIS: This scoping review will follow the Arksey and O'Malley (2005) methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Review guidelines. A comprehensive search of peer-reviewed and grey literature will be conducted from October 1989 (St. Vincent Declaration) to February 2020. Studies will be identified from electronic databases; Medline, Embase and CENTRAL (Cochrane Library). To identify further relevant articles, a hand search will be conducted using the reference lists of included studies. Two reviewers will independently screen records for relevant data and disagreements about eligibility will be resolved through consensus or arbitration by a third reviewer. A quantitative analysis will be performed to highlight key findings and thematic analysis will be used to identify emerging themes and subthemes from included studies. The key themes will highlight countries progress in terms of national-level DR service planning and screening implementation. ETHICS AND DISSEMINATION: No ethical approval is required because the scoping review methodology aims to synthesise information from publicly available resources. The results will be disseminated through conference presentations and peer-reviewed publication.

Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials.

While current lymphoma therapies induce remission in most dogs, drug-resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9-(2-phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty-three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T-cell immunophenotype and corticosteroid pre-treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG-CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.