Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

Clinical disorders affecting mesopic vision

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized

Interplay between topography, fog and vegetation in the central South Arabian mountains revealed using a novel Landsat fog detection technique

In the central South Arabian mountains of Yemen and Oman, monsoon fog interception by the endemic cloud forest is essential for ecosystem functions and services. Yet, we know little about the local factors affecting fog distributions and their cumulative effects on vegetation. To examine these relationships, we developed a novel method of high-resolution fog detection using Landsat data, and validated the results using occurrence records of eight moisture-sensitive plant species. Regression tree analysis was then used to examine the topographic factors influencing fog distributions and the topoclimatic factors influencing satellite-derived vegetation greenness. We find that topography affects fog distributions. Specifically, steep windward slopes obstruct the inland movement of fog, resulting in heterogenous fog densities and hotspots of fog interception. We find that fog distributions explain patterns of vegetation greenness, and overall, that greenness increases with fog density. The layer of fog density describes patterns of vegetation greenness more accurately than topographic variables alone, and thus, we propose that regional vegetation patterns more closely follow a fog gradient, than an altitudinal gradient as previously supposed. The layer of fog density will enable an improved understanding of how species and communities, many of which are endemic, range-restricted, and in decline, respond to local variability in topoclimatic conditions

Marathon related death due to brainstem herniation in rehydration-related hyponatraemia: a case report

Introduction: Identifying marathon runners at risk of neurological deterioration at the end of the race (within a large cohort complaining of exhaustion, dehydration, nausea, headache, dizziness, etc.) is challenging. Here we report a case of rehydration-related hyponatraemia with ensuing brain herniation. Case presentation: We report the death of runner in his 30's who collapsed in the recovery area following a marathon. Following rehydration he developed a respiratory arrest in the emergency room. He was found to be hyponatraemic (130 mM). A CT brain scan showed severe hydrocephalus and brain stem herniation. Despite emergency insertion of an extraventricular drain, he was tested for brainstem death the following morning. Funduscopy demonstrated an acute-on-chronic papilledema; CSF spectrophotometry did not reveal any trace of oxyhemoglobin or bilirubin, but ferritin levels were considerably raised (530 ng/mL, upper reference value 12 ng/mL), consistent with a previous bleed. Retrospectively it emerged that the patient had suffered from a thunderclap headache some months earlier. Subsequently he developed morning headaches and nausea. This suggests that he may have suffered from a subarachnoid haemorrhage complicated by secondary hydrocephalus. This would explain why in this case the relatively mild rehydration-related hyponatremia may have caused brain swelling sufficient for herniation. Conclusion: Given the frequency of hyponatraemia in marathon runners (serum Na <135 mM in about 13%), and the non-specific symptoms, we discuss how a simple screening test such as funduscopy may help to identify those who require urgent neuroimaging

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society