Cobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I/II Study.

BACKGROUND: The MAPK pathway is an emerging target across a number of adult and pediatric tumors. Targeting the downstream effector of MAPK, MEK1, is a proposed strategy to control the growth of MAPK-dependent tumors. OBJECTIVE: iMATRIX-cobi assessed the safety, pharmacokinetics, and anti-tumor activity of cobimetinib, a highly selective MEK inhibitor, in children and young adults with relapsed/refractory solid tumors. PATIENTS AND METHODS: This multicenter Phase I/II study enrolled patients aged 6 months to < 30 years with solid tumors with known/expected MAPK pathway involvement. Patients received cobimetinib tablet or suspension formulation on Days 1-21 of a 28-day cycle. Dose escalation followed a rolling 6 design. The primary endpoint was safety; secondary endpoints were pharmacokinetics and anti-tumor activity. RESULTS: Of 56 enrolled patients (median age 9 years [range 3-29]), 18 received cobimetinib tablets and 38 cobimetinib suspension. Most common diagnoses were low-grade glioma (LGG; n = 32, including n = 12 in the expansion cohort) and plexiform neurofibroma within neurofibromatosis type 1 (n = 12). Six patients (11 %) experienced dose-limiting toxicities (including five ocular toxicity events), which established a pediatric recommended Phase II dose (RP2D) of 0.8 mg/kg tablet and 1.0 mg/kg suspension. Most frequently reported treatment-related adverse events were gastrointestinal and skin disorders. Steady state mean exposure (Cmax, AUC0-24) of cobimetinib at the RP2D (1.0 mg/kg suspension) was ~ 50 % lower than in adults receiving the approved 60 mg/day dose. Overall response rate was 5.4 % (3/56; all partial responses in patients with LGG). CONCLUSIONS: The safety profile of cobimetinib in pediatrics was similar to that reported in adults. Clinical activity was observed in LGG patients with known/suspected MAPK pathway activation. Cobimetinib combination regimens may be required to improve response rates in this pediatric population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02639546, registered December 24, 2015.

Cataract surgery outcomes in eyes with previous radial keratotomy.

BACKGROUND/OBJECTIVES: This study shows the visual and refractive outcomes of cataract surgery in patients with previous radial keratotomy (RK). SUBJECTS/METHODS: This is a retrospective case series of 100 eyes (65 patients) with previous RK who had undergone routine cataract surgery with a monofocal intraocular lens implant (IOL) at Moorfields Eye Hospital, London, United Kingdom, between January 2004 and December 2018. RESULTS: Mean age at the time of surgery was 59.8 years; 39% eyes had ocular copathology. Best-corrected visual acuity (LogMAR; median, interquartile range) improved from 0.30 (0.22, 0.55) to 0.06 (-0.02, 0.21) in eyes without copathology, and from 0.56 (0.30, 1.00) to 0.20 (0.00, 0.20) in eyes with copathology. Haigis formula (19 eyes) resulted in a median prediction error of -0.31 D (-1.07, +0.05), versus -0.55 D (-1.23, +0.22) for Double-K SRK/T (55 eyes) and +0.93 D (0.20, 2.31) for SRK/T (18 eyes). At the final follow-up, 52.6% eyes were within 0.5 D and 68.4% within 1 D of the predicted spherical equivalent for Haigis, versus 32.7% and 52.7% for Double-K SRK/T, and 27.8% and 38.9% for SRK/T. The most frequent complication was RK incision dehiscence (8%). CONCLUSIONS: Although the best-corrected visual acuity outcomes compare with the UK national benchmarks, significantly fewer eyes with previous RK achieved the level of unaided distance visual acuity to allow spectacle independence. Surgeons should be aware of the increased likelihood of wound dehiscence and plan surgery accordingly. Haigis formula tended to have a better predictability of the postoperative spherical equivalent and, since introduced, was the preferred choice for IOL calculation in this group of patients.

Acceptability of immediate sequential bilateral cataract surgery (ISBCS) in a public health care setting before and after COVID-19: a prospective patient questionnaire survey.

OBJECTIVE: To ascertain patient acceptance of immediate sequential bilateral cataract surgery (ISBCS) in the National Health Service (NHS). METHODS: A survey was devised using a 5-point Likert scale for questions related to ISBCS, which patients undertook during their cataract outpatient appointment pre-COVID-19 lockdown and by telephone during the lockdown. RESULTS: Questionnaires were completed for 267 patients. Most respondents were aged over 71 (51%) and were female individuals (60%). Forty-five per cent agreed/strongly agreed with opting for ISBCS. A positive correlation was identified between opting for ISBCS and convenience to the patient (r=0.76, p<0.01) and family/carer/partner (r=0.71, p<0.01) and wanting to limit numbers of hospital visits (r=0.57, p<0.01). Fifty per cent agreed/strongly agreed that they were worried about the risk of simultaneous bilateral ocular complications, with this correlating with being less likely to opt for ISBCS (r=-0.49, p<0.01) and being scared of ISBCS (r=0.67, p<0.01). During COVID-19 lockdown, patients were less likely to want to minimise the time taken off work (p<0.05) and less intolerant of a prolonged hospital visit (p<0.05). Only 23% of respondents agreed/strongly agreed that they had familiarity with ISBCS. CONCLUSIONS: ISBCS was acceptable to 45% of our sampled population, suggesting limited routine implementation in the NHS is possible. Convenience and reduction in hospital visits appeared to contribute to this acceptance. Half of the patients expressed concern regarding bilateral complications and such concerns need addressing. Some attitudes did appear to change during the COVID-19 lockdown period. The familiarity of the concept of ISBCS is low suggesting the need for patient education.

FULL DIAGNOSTIC VITRECTOMY WITH POSTERIOR VITREOUS DETACHMENT INDUCTION FOR THE DIAGNOSIS OF VITRITIS DUE TO UNCERTAIN ETIOLOGY.

PURPOSE: To report on the diagnostic outcomes and safety of full diagnostic vitrectomy (FDV) with surgical posterior vitreous detachment induction for diagnosing vitritis of uncertain etiology. METHODS: Forty-nine patients underwent primary FDV using the cassette washings for histopathological analysis. In addition, an undiluted core vitreous sample was obtained for microbial analysis in suspected infective cases. Cases were retrospectively given a diagnosis of inflammatory, infective, or neoplastic based on the results at final follow-up and the outcome of primary FDV categorized as diagnostic or nondiagnostic. The success of FDV was evaluated in relation to the final diagnosis. The need for additional intraocular biopsies and intraoperative or postoperative complications was also recorded. RESULTS: Full diagnostic vitrectomy was diagnostic in 26/49 cases (53%) and nondiagnostic in 23 (47%). The diagnostic success rate was greatest in neoplastic (16/20, 80%) and infective cases (9/13, 69%). Seven cases (14%) required additional biopsies to establish the diagnosis, and in 15/49 cases (31%), no cause of vitritis was identified. Intraoperative retinal breaks occurred in 3/49 cases (6%) and retinal detachment in 1/49 cases (2%). Three of 49 cases (6%) developed transiently elevated intraocular pressure postoperatively. CONCLUSION: Full diagnostic vitrectomy in combination with an undiluted core vitreous biopsy for suspected infections is safe and effective at securing a diagnosis in vitritis, particularly in cases of neoplasia.

Knowledge of umbilical cord blood banking among obstetricians and mothers in Anand and Kheda District, India.

BACKGROUND: To assess the knowledge of obstetricians and expectant mothers towards UCB banking and their awareness regarding pros and cons of the process. METHODS: Questionnaires from a previously published study were modified contextually and translated into vernacular language (Gujarati). The questionnaires were distributed among 200 obstetricians, of which 100 responded and 100 mothers were in Anand and Kheda districts of India. Informed consent was taken for both. RESULTS: Mean (SD) age of obstetricians was 47.5 years (11.14) with mean (SD) work experience of 19.72 years (9.94). Almost all were aware of collection procedure for UCB and felt that UCB banking is useful. Thirty obstetricians thought that stored blood can be used in conditions of Autism, Duchenne Muscular Dystrophy and all genetic conditions. Sixty-three were aware of the procedure technique. Majority felt that the process was feasible and would do it for their own child. All the 100 mothers approached consented for the study with average age (SD) of 26.88 (4.17). Many were not aware of such a procedure and were not certain about the usefulness of the procedure. Seventy-six did not know the conditions in which the stored blood can be used. Only 4 mothers/family members had opted for UCB banking, whereas 27 expressed their willingness to recommend UCB to another mother. Five Muslim women wanted UCB but could not pursue it due to religious norms. CONCLUSION: The level of understanding among obstetricians was not commensurate with the amount of faith with which they promoted UCB banking.

Variations in Treatment Delivery for Patients with Neovascular AMD in the UK: Results from an Ophthalmology Trainee Clinical Research Network Study.

INTRODUCTION: The aim of this study was to determine treatment delivery patterns for patients with neovascular age-related macular degeneration (nAMD) across the UK through an ophthalmology trainee research network delivered observational study. METHODS: Data were collected via an online tool by potential research collaborators identified by the Ophthalmology Trainee Clinical Trial Network (OCTN). Collaborators were asked to comment on periprocedural practices of treatment of nAMD in their eye unit including treatment location and injectors, clinical assessment and routine observation in patients undergoing intravitreal treatment. RESULTS: Data were available from 26 units around the United Kingdom. Survey methodology refinement was approximately 3 months, and the average response time was 4.9 ± 2.4 days. The majority of responders confirmed that treatment was undertaken as a "one-stop" service (n = 15, 58%), delivered in a clean room (n = 23, 88%). In the majority of units, doctors administered injections (n = 24, 92%), but significant treatment was also given by nurse injectors (n = 21, 81%). All collaborators reported that patients underwent visual acuity testing and optical coherence tomography imaging at all visits, but other imaging including fundus fluorescein angiography (FFA) did not take place in all cases (n = 17, 65%) and only at baseline visit. CONCLUSIONS: These results demonstrate the feasibility of conducting ophthalmology trainee led and delivered observational studies. Our results show that FFA is not routinely used in the diagnosis of nAMD in the units sampled; most injections are carried out in a clean room, and ophthalmic nurses delivering injections is a highly prevalent model of care in the UK.

Conjunctival Angioimmunoblastic T-Cell Lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) represents an uncommon variant of T-cell lymphomas and most often presents insidiously with systemic symptoms. This report constitutes the first documented case of conjunctival AITL, masquerading as nodular episcleritis, and describes both the clinical and pathological findings. Furthermore, conjunctival T-cell lymphoma in general remains a rare occurrence, and a survey of previously reported cases reveals a wide variation in clinical presentation. A high index of suspicion, thorough examination and conjunctival biopsy are essential to reaching the diagnosis of conjunctival lymphoma.