Genetic Diagnosis of Retinoblastoma Using Aqueous Humour-Findings from an Extended Cohort.

The identification of somatic RB1 variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) derived from aqueous humour (AH) can be used to identify somatic RB1 pathogenic variation. Here we report RB1 pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected RB1 pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic RB1 pathogenic variants in retinoblastoma patients undergoing conservative treatment.

Long-term Efficacy of Mitomycin C Augmented Trabeculectomy in a Mixed Pediatric Glaucoma Cohort.

PRECIS: This paper reports a retrospective consecutive case series investigating the efficacy of Mitomycin C-augmented trabeculectomy in the treatment of primary and secondary pediatric glaucoma in a mixed etiology, multiethnic cohort of patients. PURPOSE: To evaluate the long-term efficacy and safety of Mitomycin C-augmented trabeculectomy in a mixed, tertiary-referral, pediatric glaucoma cohort. METHODS: Retrospective consecutive review of all children (37 eyes) undergoing Mitomycin C-augmented trabeculectomy by a single surgeon between 2008 and 2016. Seventeen eyes (45.9%) had primary congenital glaucoma, and 20 eyes (54.1%) had secondary glaucoma. The median age at surgery was 11 months (range, 2 to 146). The mean follow-up was 69.2±4.7 months (range, 3.5 to 107.9). RESULTS: Overall, trabeculectomy was successful in 80.6% of eyes at 12 months, 60.5% at 3 years, and 57.5% at 5 years. 45.9% cases (17 eyes) required further laser or surgery for uncontrolled intraocular pressure (IOP) and were therefore deemed as failures. The time to failure ranged from 0.4 to 65.1 months (mean, 22.2±5.1 mo). The proportion of children achieving visual acuity of 1.0 LogMAR equivalent or better increased from 43.2% preoperatively to 63.6% at 1 year and 68% at 5 years. The mean IOP reduced from 24.85±0.88 mm Hg preoperatively to 15.14±0.94 mm Hg at 3 months (39% reduction) and 17.42±1.08 mm Hg at 5 years (30% reduction). IOP-lowering medication requirement reduced from 4.14±0.20 agents preoperatively to 0.84±0.22 at 3 months (80% reduction) and 1.78±0.36 at 5 years (57% reduction). There were no sight-threatening complications such as hyphaema, bleb leak, chronic hypotony, endophthalmitis, retinal detachment, or loss of light perception. CONCLUSIONS: This study provides valuable evidence that Mitomycin C-augmented trabeculectomy is safe and effective as a treatment of primary or secondary pediatric glaucoma, with particularly encouraging results in cases of secondary glaucoma. Trabeculectomy offers the potential for delaying or avoiding glaucoma drainage device surgery in a significant proportion of children.

Exploring The Current Management Idiopathic Intracranial Hypertension, And Understanding The Role Of Dural Venous Sinus Stenting.

Idiopathic Intracranial Hypertension (IIH) is a debilitating disorder characterised by raised intracranial pressure (ICP), papilloedema with the potential risk of permanent visual loss, and headaches that are profoundly disabling and reduce the quality of life. The first consensus guidelines have been published on investigation and management of adult IIH and one key area of uncertainty is the utility of dural venous sinus stenting for the management of headache and visual loss. There are an increasing number of series published and to help understand the successes and complications. During a patient physician priority setting, the understanding of the best type of intervention to treat IIH was assigned to the top 10 of most desired research questions for the disease. Ultimately randomised clinical trials (RCTs) in neurovascular stenting for IIH would be instructive, as the literature to date may suffer from publication bias. Due to the increasing incidence of IIH, there is no better time to systematically investigate interventions that may reverse the disease process and achieve remission. In this review we discuss the pathophysiology of IIH in relation to venous sinus stenosis, the role of venous sinus stenting with a review of the relevant literature, the advantages and disadvantages of stenting compared with other surgical interventions, and the future of stenting in the treatment of IIH.

Reviewing the Pathophysiology Behind the Advances in the Management of Giant Cell Arteritis.

Improving understanding of the underlying pathophysiology of giant cell arteritis (GCA) is transforming clinical management by identifying novel avenues for targeted therapies. One key area of concern for both clinicians and patients with GCA is glucocorticoid (GC) morbidity. The first randomised controlled trials of targeted treatment to reduce cumulative GC use in GCA have been published, with tocilizumab, an interleukin (IL)-6 receptor inhibitor, now the first ever licensed treatment for GCA. Further potential therapies are emerging owing to our enhanced understanding of the pathophysiology of the disease. Other improvements in the care of our patients are rapid access pathways and imaging techniques, such as ultrasound, which are becoming part of modern rheumatology practice in the UK, Europe and beyond. These have been highlighted in the literature to reduce delay in diagnosis and improve long-term outcomes for those investigated for GCA.

How to use the direct ophthalmoscope.

Ophthalmoscopy and red reflex examination are core medical skills required to identify sight-threatening and life-threatening disease. We discuss the predictive utility and limitations of findings with an ophthalmoscope and tips as to how to optimise these. We outline important considerations in three clinical scenarios: an abnormal red reflex, an abnormal optic disc and retinal haemorrhages in the context of child protection concerns.