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AIM: To compare the mydriatic efficacy of an ophthalmic insert (Mydriasert, MY) versus phenylephrine and tropicamide (PT) eye drops. METHODS: Two controlled, prospective, randomized, single-blind studies were performed. In the first study, a total of 80 eyes from 40 outpatient-clinic patients were analyzed. PT drops were applied to the right eye, and a MY device was inserted in the left eye for 30min. Time until maximal pupil dilation for each eye was then assessed. In the second study, 80 eyes from 80 patients undergoing cataract surgery were analyzed. Pupil dilation was achieved using either PT drops three-times for one hour prior to surgery (40 patients), or a MY device was inserted one hour prior to surgery (40 patients). RESULTS: In the first study, MY achieved superior mydriasis compared to PT eye drops at 90min (9.04 +/- 1.33mm vs 8.78 +/- 1.37mm, P=0.012). However MY took longer than PT drops to achieve maximal dilation, and mydriasis was inferior in eyes with MY compared to PT drops at 30min (7.21 +/- 1.73mm vs8.22 +/- 1.43mm, P < 0.001), the two groups only becoming similar by 60min (8.85 +/- 1.44mm vs8.71 +/- 1.27mm, P=0.236). In the second study, both MY and PT achieved similar levels of mydriasis at the beginning of surgery (8.75 +/- 0.76mm with MY vs8.77 +/- 0.63mm with PT), and also at the end of surgery (7.96 +/- 1.06mm with MY vs 8.32 +/- 0.72mm with PT), with no significant difference between groups (P=0.08). MY was well tolerated and cardiovascular effects were not influenced by dilation method. CONLUSION: MY could be a safe and efficacious alternative for mydriasis. The mydriatic effect of MY is as good as conventional PT eye drops after 60min, and is superior after 90min. MY also maintains good pupil dilation during cataract surgery.

BACKGROUND: Meningeal carcinomatosis (MC) is a rare complication associated with hematologic and solid tumors. MC develops when malignant cells gain access to the leptomeningeal space, producing several clinical symptoms. Loss of vision and ocular motility deficit are the most frequent ocular symptoms reported. Fundus examination usually appears normal, although optic nerve alterations like optic atrophy or papilledema have been described. MC diagnosis is usually completed by magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Indicated treatment for MC usually involves intrathecal chemotherapy combined with radiotherapy, although survival rate is extremely low. CASE PRESENTATION: A 66-year old man with stage IV metastatic lung adenocarcinoma, presented to the Ophthalmology Department with a two-month history of double vision, soft headaches and dizziness episodes. The patient presented a best visual corrected acuity of 0.7 in his right eye and 0.8 in his left eye. Diplopia was corrected with 6-prism diopters base-out prism in right eye. Funduscopy showed a bilateral papilledema, juxtapapillary exudates and splinter hemorrhages. Brain MRI showed a diffuse leptomeningeal enhancement in cortical sulcus. Lumbar puncture was performed and cerebrospinal fluid (CSF) cytology revealed malignant cells compatible with a diagnosis of MC. Intrathecal chemotherapy was administered. CONCLUSION: MC is a serious complication of systemic cancer patients, involving a poor prognosis. Early diagnosis is extremely important, although treatment is frequently aimed to reduce the symptoms and extend survival. Eye symptoms may be the chief complaint, so MC should be considered in any patient with vision loss or diplopia accompanied by neurologic symptoms and in the absence of an intraocular cause, especially in the context of systemic cancer.

Background: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826. Methods: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries. Eligible patients were aged 18 years or older with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy (previous radiosensitising chemotherapy was allowed) and not amenable to curative treatment and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) centrally by means of an interactive voice response system in a double-blind manner to receive either pembrolizumab 200 mg or placebo every 3 weeks intravenously for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 plus cisplatin 50 mg/m2 or carboplatin area under the curve 5 mg/mL per min, intravenously) with or without bevacizumab 15 mg/kg every 3 weeks intravenously. Randomisation (block size of 4) was stratified by metastatic disease at diagnosis, planned bevacizumab use, and PD-L1 combined positive score. Patients, investigators, and other study personnel involved in study treatment administration or clinical evaluation of patients were unaware of treatment group assignments. PRO instruments were the EORTC Quality-of-Life-Core 30 (QLQ-C30), the EORTC cervical cancer module (QLQ-CX24), and the EuroQol-5 dimension-5 level (EQ-5D-5L) visual analogue scale, each collected before treatment at cycles 1–14 and every other cycle thereafter. Primary endpoints were overall survival and progression-free survival per RECIST version 1.1 by investigator review. Change from baseline in QLQ-C30 global health status (GHS)–quality of life (QoL) was a prespecified secondary endpoint and was assessed in the PRO full analysis population (all patients who received at least one dose of study treatment and completed at least one post-baseline PRO assessment). Other PRO analyses were protocol-specified exploratory endpoints. The study is registered with ClinicalTrials.gov, NCT03635567, and is ongoing. Findings: Between Nov 20, 2018, and Jan 31, 2020, of 883 patients screened, 617 were randomly assigned (pembrolizumab group, n=308; placebo group, n=309). 587 (95%) of 617 patients received at least one dose of study treatment and completed at least one post-baseline PRO assessment and were therefore included in the PRO analyses (pembrolizumab group, n=290; placebo group, n=297). Median follow-up was 22·0 months (IQR 19·1–24·4). At week 30, QLQ-C30 completion was 199 (69%) of 290 patients in the pembrolizumab group and 168 (57%) of 297 patients in the placebo group; compliance was 199 (94%) of 211 and 168 (90%) of 186, respectively. The least squares mean change in QLQ-C30 GHS–QoL score from baseline to week 30 was −0·3 points (95% CI −3·1 to 2·6) in the pembrolizumab group and −1·3 points (−4·2 to 1·7) in the placebo group, with a between-group difference in least squares mean change of 1·0 point (95% CI −2·7 to 4·7). Median time to true deterioration in GHS–QoL was not reached (NR; 95% CI 13·4 months–NR) in the pembrolizumab group and 12·9 months (6·6–NR) in the placebo group (hazard ratio 0·84 [95% CI 0·65–1·09]). 122 (42%) of 290 patients in the pembrolizumab group versus 85 (29%) of 297 in the placebo group had improved GHS–QoL at any time during the study (p=0·0003). Interpretation: Addition of pembrolizumab to chemotherapy with or without bevacizumab did not negatively affect health-related quality of life. Along with the efficacy and safety results already reported from KEYNOTE-826, these data support the benefit of pembrolizumab and the value of immunotherapy in patients with recurrent, persistent, or metastatic cervical cancer.

Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1-staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis.In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P = 0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively).Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. (Funded by Merck Sharp and Dohme; KEYNOTE-826 ClinicalTrials.gov number, NCT03635567.).