Identification of pathogenic RB1 variants aids in the clinical management of families with retinoblastoma. We routinely screen DNA for RB1 variants, but transcript analysis can also be used for ...variant screening, and to help decide variant pathogenicity. DNA was screened by conformation analysis followed by Sanger sequencing. Large deletion/insertions were detected by polymorphism analysis, MLPA and quantitative-PCR. Methylation-specific PCR was used to detect hypermethylation. RNA screening was performed when a DNA pathogenic variant was missing, or to determine effects on splicing.Two hundred and thirteen small coding variants were predicted to affect splicing in 207 patients. Splice donor (sd) variants were nearly twice as frequent as splice acceptor (sa) with the most affected positions being sd + 1 and sa-1. Some missense and nonsense codons altered splicing, while some splice consensus variants did not. Large deletion/insertions can disrupt splicing, but RNA analysis showed that some of these are more complex than indicated by DNA testing. RNA screening found pathogenic variants in 53.8% of samples where DNA analysis did not. RB1 splicing is altered by changes at consensus splice sites, some missense and nonsense codons, deep intronic changes and large deletion/insertions. Common alternatively spliced transcripts may complicate analysis. An effective molecular screening strategy would include RNA analysis to help determine pathogenicity.
To investigate the clinical findings and differential diagnosis of incidental unilateral discoid maculopathy in a case series of children.
The medical records and retinal imaging of children referred ...to a single center for flat, well circumscribed, hypopigmented discoid macular lesion in the left eye were reviewed retrospectively.
Three children (age range, 4-11 years; 2 female), with no subjective ophthalmic complaints, were referred for investigation of a flat, well-circumscribed, hypopigmented discoid macular lesion in the left eye. Case 1 had a history of viral mesenteric adenitis, and case 2 had a history of hand, foot, and mouth disease. For case 3, no previous history of systemic viral infection was established. Snellen visual acuity was 20/20 for all 3 children. The lesion was located superior to the fovea for case 1 and centered to the fovea for cases 2 and 3, all in the left eye. In all 3 patients, hyperautofluorescent changes were noted around the edges of the lesion, which was roughly discoid. OCT showed subtle changes of the interdigitation zone and retinal pigment epithelium (RPE) for cases 1 and 2. In case 3 the presence of hyperreflective, hypertrophic tissue at the level of the interdigitation zone and/or the RPE was noted.
In these 3 children with subclinical, unilateral discoid maculopathy sharing common features and identified incidentally, previous viral illness may have been causative. These cases may represent resolved unilateral acute idiopathic maculopathy.
Ocular medulloepithelioma (diktyoma) is a rare and potentially malignant paediatric tumour of the non-pigmented ciliary epithelium. Adjuvant chemotherapy can be given in advanced cases, but the ...indications and regimens remain to be defined. The aim was to identify whether adjuvant chemotherapy offers treatment benefit in advanced ocular medulloepithelioma.
This was a retrospective case series of subjects referred to a single specialist ocular oncology centre for advanced ocular medulloepithelioma subsequently treated with enucleation, including those needing adjuvant systemic vincristine, etoposide and carboplatin. A case-note review was performed for included subjects meeting referral criteria. The outcomes were histopathology characteristics, recurrence, metastases and survival.
Between March 2010 and June 2017, four male patients (mean age 31 months) underwent enucleation for ocular medulloepithelioma. Adjuvant chemotherapy was commenced in 3 patients (75%) due to malignant histopathological features. With a mean follow-up time of 81.5 months (median 71 months, range 49-135 months) none of the patients have had recurrence, metastases or death from the tumour.
This series is unique in reporting the management of advanced malignant ocular medulloepithelioma with adjuvant systemic vincristine, etoposide and carboplatin for advanced tumours with malignant features. This regimen appears to be safe and may be effective in preventing metastatic spread.
The widely accepted model for atrial fibrillation (AF) ablation involves overnight hospital stay post-procedure. Day case AF ablation has been carried out at Royal Papworth Hospital (RPH) since early ...2017. We evaluated the feasibility, safety and efficacy of day case AF ablation at RPH.
This was a retrospective, single-centre study of consecutive AF ablations at RPH between March 2017 and April 2018. Demographic, procedural and outcome data were analysed.
Over the study period, 452 AF ablations were performed in 448 patients. One hundred and twenty-nine (129) (28.5%) were planned day cases; of these 128 were discharged on the same day. Two hundred and eighty-three (283) procedures resulted in at least one night admission. There was no significant difference in age or sex between the groups. Of note, day case procedures were significantly shorter, more likely to commence in the morning and less likely to require general anaesthetic than overnight stays. Patients listed as day cases also had less far to travel. The overall complication rate was 3.3%, with no significant difference between groups. Follow-up data was available for 448 cases (99.1%). Procedural success rates were comparable between groups. The overall cost saving attributable to providing AF ablation as a day case was £67,200 over the 13-month period.
Day case AF ablation is efficacious and associated with a low event rate, even without strict standardisation of patient selection or procedural protocols, in a high-volume centre. Substantial reduction in health care expenditure can be achieved with more widespread implementation of outpatient AF ablation.
Intra-arterial chemotherapy (IAC) for retinoblastoma has been documented as causing visual loss and ocular motility problems. A lack of safety data has precluded its acceptance in all centres.
...Retrospective cohort study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola and relapsed following systemic chemotherapy. All required IAC. The correlation of complications with doses of melphalan +/- topotecan used and putative catheterisation complications was assessed. Ocular complications were determined using vision, macular (including pattern visual evoked potentials (PVEPs)), retinal electroretinograms (ERGs) and ocular motility functions. Efficacy (tumour control) was also assessed.
All eyes had age appropriate doses of melphalan with five having additional doses of topotecan. Severe physiological reactions requiring adrenaline were seen in six patients during the catheterisation procedure. Difficulty was documented in accessing the ophthalmic artery in 7/27 catheterisations. The median/mean number of courses of chemotherapy was three. No child had severe visual loss as assessed by age appropriate tests (median follow-up 20.9 months, range 3.7-35.2 months). One child had nasal choroidal ischaemia and a sixth nerve palsy. Post-IAC PVEPs were performed in eight and reported as normal. All post-IAC ERGs were normal apart from one (total dose 20 mg melphalan 0.8 mg topotecan). Tumour control was achieved in six of nine cases.
The proportion of visual and ocular motility complications may be reduced by providing age-adjusted doses of melphalan. Dose rather than complications from catheterisation is the most important risk factor for ocular injury.
Retinoblastoma (RB) is a primary childhood eye cancer. HMGA2 shows promise as a molecule for targeted therapy. The involvement of miRNAs in genome-level molecular dys-regulation in HMGA2-silenced RB ...cells is poorly understood. Through miRNA expression microarray profiling, and an integrated array analysis of the HMGA2-silenced RB cells, the dysregulated miRNAs and the miRNA-target relationships were modelled. Loop network analysis revealed a regulatory association between the transcription factor (SOX5) and the deregulated miRNAs imiR-29a, miR-9*, miR-9-3). Silencing of HMGA2 deregulated the vital oncomirs (miR-7, miR-331, miR-26a, miR-221, miR-17∼92 and miR-106b∼25) in RB cells. From this list, the role of the miR-106b∼25 cluster was examined further for its expression in primary RB tumor tissues (n = 20). The regulatory targets of miR-106b∼25 cluster namely p21 (cyclin-dependent kinase inhibitor) and BIM (pro-apoptotic gene) were elevated, and apoptotic cell death was observed, in RB tumor cells treated with the specific antagomirs of the miR-106b∼25 cluster. Thus, suppression of miR-106b∼25 cluster controls RB tumor growth. Taken together, HMGA2 mediated anti-tumor effect present in RB is, in part, mediated through the miR-106b∼25 cluster.
Purpose. Congenital retinal macrovessels (CRM) represent rare aberrant vasculature of the retinal vessels that can supply or drain the macula. In this report, the optical coherence tomography ...angiography features of a congenital retinal macrovessel are discussed. Methods. The history and examination findings are presented alongside swept-source OCT angiography with corresponding B scan and en face OCT imaging. Patients. The case is a 12-year-old female patient with excellent best-corrected visual acuity in both eyes. Results. Swept-source OCT angiography demonstrated considerable loss of the foveal avascular zone at the levels of the superficial and deep capillary plexus. Discussion. In this case there was no detrimental effect on vision despite anatomical loss of the foveal avascular zone.
PURPOSETo study the frequency and possible causes of severe corneal opacities in premature infants undergoing retinopathy of prematurity (ROP) screening in the neonatal intensive care unit (NICU) at ...a single institution. METHODSThe medical records of all infants screened for ROP in the NICU between January 2015 and March 2019 were reviewed retrospectively. Criteria for screening were gestational age (GA) of <32 weeks or birth weight (BW) <1501 g. Characteristics of premature infants with severe corneal opacities were extracted from the record. RESULTSA total of 445 premature infants were screened during the 51-month period. The prevalence of severe corneal opacities was 1.4% (6 infants). The median GA of the affected infants was 24.5 weeks (range, 23-32), and the mean BW was 624 g (range, 500-860 g). Two infants had lagophthalmos; their corneal opacity was unilateral. All the infants were under continuous positive airway pressure (CPAP) for a prolonged period. All 4 infants with bilateral corneal opacities required treatment for severe ROP-laser (n =1), bevacizumab injection (n = 1), or both (n = 2). CONCLUSIONSSevere corneal opacities in premature infants are rare but potentially sight threatening, because they can hinder the retinal examination. Lagophthalmos-related exposure keratopathy is an obvious risk factor. CPAP therapy may be another risk factor leading to the development of severe corneal opacities. Identification of infants at risk and prompt commencement of lubricants is necessary to avoid long-term corneal opacities.
Eye salvage rate for group D retinoblastoma using intravenous chemotherapy (IVC) as a primary modality is <50%. To report on 13 years' experience with the use of primary IVC for group D ...retinoblastoma.
A retrospective analysis of 64 group D eyes (52 patients) treated with primary IVC, from 2002 to 2014.
The median age at presentation was 11.0 months (mean: 18.6, range: 0.6-144.0), 35 (67%) patients had bilateral disease, 38 (73%) germline disease and 8 (15%) cases were familial. In addition to IVC, patients received a median number of three treatments (mean: 6, range: 0-24), including thermotherapy/cryotherapy, plaque radiotherapy, intra-ophthalmic artery chemotherapy (IAC) and/or intravitreous chemotherapy. External beam radiotherapy (EBRT) was used in five eyes, all of which were eventually enucleated. In a median follow-up time of 55 months (mean: 64, range: 14-156), 63% of eyes were salvaged. By the Kaplan-Meier survival analysis, globe salvage rate was 83%, 70%, 59% and 45% at 1, 3, 5 and 10 years, respectively. There were no cases of metastatic spread from intraocular retinoblastoma and no deaths. IVC-related adverse events included febrile neutropenia in 21 (40%) patients and anaphylactic reaction to carboplatin in 2 (4%), all conservatively resolved. Of the patients receiving IAC, third and sixth nerve palsies were documented in two (10%) and one (5%) eyes, respectively.
Primary IVC for group D eyes, with adjuvant treatments as required, was found to be a safe and efficient approach, achieving 63% eye salvage rate, no metastatic spread from intraocular retinoblastoma and no deaths. IAC has now replaced EBRT as a successful salvage treatment.
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