Confidence of UK Ophthalmology Registrars in Managing Posterior Capsular Rupture: Results from a National Trainee Survey

Introduction: To establish the level of confidence amongst UK ophthalmology specialist registrars (residents) in managing posterior capsule rupture (PCR) during cataract surgery. / Methods: An online nine-item questionnaire was distributed to all registrars, recruited nationwide via regional representatives. Data collected included stage of training, number of completed cataract operations, cumulative PCR rate, number of PCRs independently managed, understanding of vitrectomy settings and fluidic parameters and access to simulation. Respondents self-evaluated their confidence in managing PCR with vitreous loss. / Results: Complete responses were obtained from 248 registrars (35% response rate). Mean number of phacoemulsification procedures performed was 386. For senior registrars (OST 6–7), 35 out of 70 (50%) felt confident to manage PCR independently and 55 out of 70 (78.6%) were either quite confident or very confident at deciding when to implant an intraocular lens during PCR management. Lower confidence levels were noted for junior trainees (OST 1–2). Over 65% of survey respondents had access to relevant simulation. / Conclusions: Our results represent the largest UK survey analysing the confidence of PCR management amongst registrars. Confidence improves with duration of training and increased exposure to management of PCR. However, 50% of senior registrars still lacked confidence to independently manage PCR and vitreous loss. A specific competency-based framework, potentially using a simulator or simulating a PCR event, incorporated into the curriculum may be desirable

Hydroxychloroquine and short-course radiotherapy in elderly patients with newly diagnosed high-grade glioma: a randomized phase II trial

Background: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers. Methods: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation). Patients aged at least 70 years with newly diagnosed high-grade glioma deemed suitable for short-course radiotherapy with an ECOG performance status of 0–1 were included. Radiotherapy treatment consisted of 30 Gy, delivered as 6 fractions given over 2 weeks (5 Gy per fraction). Hydroxychloroquine was given as 200 mg orally b.d. from 7 days prior to radiotherapy until disease progression. The primary endpoint was 1-year overall survival (OS). Secondary endpoints included progression-free survival (PFS), quality of life, and toxicity. Results: Fifty-four patients with a median age of 75 were randomized between May 2013 and October 2016. The trial was stopped early in 2016. One-year OS was 20.3% (95% confidence interval [CI] 8.2–36.0) hydroxychloroquine group, and 41.2% (95% CI 18.6–62.6) radiotherapy alone, with a median survival of 7.9 and 11.5 months, respectively. The corresponding 6-month PFS was 35.3% (95% CI 19.3–51.7) and 29.4% (95% CI 10.7–51.1). The outcome in the control arm was better than expected and the excess of deaths in the hydroxychloroquine group appeared unrelated to cancer. There were more grade 3–5 events in the hydroxychloroquine group (60.0%) versus radiotherapy alone (38.9%) without any clear common causation. Conclusions: Hydroxychloroquine with short-course radiotherapy did not improve survival compared to radiotherapy alone in elderly patients with glioblastoma

Overcoming challenges of translating deep- learning models for glioblastoma: the ZGBM consortium

Objective: To report imaging protocol and scheduling variance in routine care of glioblastoma patients in order to demonstrate challenges of integrating deep-learning models in glioblastoma care pathways. Additionally, to understand the most common imaging studies and image contrasts to inform the development of potentially robust deep-learning models. Methods: MR imaging data were analysed from a random sample of five patients from the prospective cohort across five participating sites of the ZGBM consortium. Reported clinical and treatment data alongside DICOM header information were analysed to understand treatment pathway imaging schedules. Results: All sites perform all structural imaging at every stage in the pathway except for the presurgical study, where in some sites only contrast-enhanced T 1-weighted imaging is performed. Diffusion MRI is the most common non-structural imaging type, performed at every site. Conclusion: The imaging protocol and scheduling varies across the UK, making it challenging to develop machine-learning models that could perform robustly at other centres. Structural imaging is performed most consistently across all centres. Advances in knowledge: Successful translation of deep-learning models will likely be based on structural post-treatment imaging unless there is significant effort made to standardise non-structural or peri-operative imaging protocols and schedules

Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom

\ua9 The Author(s) 2024.Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. Methods: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. Results: 132 pts were included. Median age was 56 years (28–91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5–6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. Conclusion: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience

Factors Affecting COVID-19 Outcomes in Cancer Patients: A First Report From Guy's Cancer Center in London

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months before COVID-19 [OR: 1.74 (95% CI: 0.71–4.26)], presenting with fever [6.21 (1.76–21.99)], dyspnea [2.60 (1.00–6.76)], gastro-intestinal symptoms [7.38 (2.71–20.16)], or higher levels of C-reactive protein [9.43 (0.73–121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28–10.91)], receiving palliative treatment [5.74 (1.15–28.79)], having an initial cancer diagnosis >24 months before [2.14 (1.04–4.44)], dyspnea [4.94 (1.99–12.25)], and increased CRP levels [10.35 (1.05–52.21)] were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01–0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients

Toxicity profile of bevacizumab in the UK Neurofibromatosis Type 2 cohort

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis Type 2(NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event(CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32female), median age 24.5 years (range 11-66years), were followed for a median of 32.7 months (range 12.0–60.2months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24%) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5%) had proteinuria. Of 36 patients followed for 36 months, 78% were free from hypertension and 86% were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be predictors of development of hypertension with dose of 7.5mg/kg three weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy

Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing

Purpose We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). Methods Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. Results There was no evidence for usefulness of old criteria “glioma“ or “neurofibroma.” “Ependymoma” had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. Conclusions The present study confirms important deficiencies in NF2 diagnostic criteria. The term “glioma” should be dropped and replaced by “ependymoma.” Similarly “neurofibroma” should be removed. Dropping “sibling” from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS

Six year outcomes of combined phacoemulsification surgery and endoscopic cyclophotocoagulation in refractory glaucoma

PURPOSE: This study is to describe the 6-year results of combined phacoemulsification surgery and endoscopic cyclophotocoagulation (Phaco-ECP) surgery in patients with uncontrolled glaucoma and no previous glaucoma surgery. METHODS: This is a retrospective case series of 84 eyes. The primary outcome measure was intraocular pressure (IOP) reduction 6 years postoperatively. Secondary outcome measures were the cumulative probability of failure of the surgical procedure at 6 years. Failure was defined as IOP higher than 21 mm Hg or lower than 6 mm Hg or IOP not reduced by 20% from baseline at the 1, 2, 3, 4, 5, or 6-year time points or further laser or other surgery to reduce IOP at any timepoint. RESULTS: There was a statistically significant decrease in mean IOP from 18.9 mmHg pre-operatively to 13.7, 12.8, 13.0, 12.7, 12.5, and 12.3 mmHg at the 1, 2, 3, 4, 5, and 6 years post-operatively respectively (p < 0.001). Fifty-seven (68%) reached criteria for failure by 6 years. In 36% of cases, this was due to inadequate IOP control, whereas 32% required further laser or surgery. When we excluded patients who only had selective laser trabeculoplasty rather than further surgery, the failure rate reduced to 51%. Eleven percent had a post-operative complication, 2.4% requiring further surgical intervention. CONCLUSIONS: At 6 years postoperatively, combined phaco-ECP achieved a significant reduction in IOP in patients with uncontrolled glaucoma and no previous drainage surgery. Significant complications were uncommon, but 68% was classified as surgical failures by the six year point.Published version, accepted version (12 month embargo)RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted (12 month embargo)

Ocular manifestations of tuberculosis: an update

Tuberculosis (TB) remains a major global health burden and has both pulmonary and extra-pulmonary manifestations. One well-recognised and complex extra-pulmonary form is ocular TB, with its diverse extra- and intra-ocular presentations and often without signs of systemic illness. These could be caused directly by Mycobacterium tuberculosis and inflammation or represent a delayed immune response. Epidemiological data on the true prevalence of ocular TB is scanty and varied in different parts of the world. This is due to lack of a uniform diagnostic criteria as well as difficulties in confirming the diagnosis with traditional laboratory methods. A variety of investigations including imaging, blood tests and biopsies can be used to predict and diagnose ocular involvement in tuberculosis. Our expert review seeks to identify key clinical and laboratorial features and provide a literature update that may facilitate diagnosis of intra-ocular tuberculosis