Papilloedema: a highly specific predictor of raised intracranial pressure in a complex neurosurgical paediatric cohort.

PURPOSE: Papilloedema is recognised as an indicator of raised intracranial pressure, although there is a paucity of literature describing the utility of fundoscopy in screening for raised ICP in children with craniofacial synostosis, particularly young children. We sought to investigate the association of optic disc morphology with ICP in children, and to define the sensitivity and specificity of papilloedema as a clinical indicator of raised ICP and determine if age, or underlying conditions impact the findings. METHOD: Retrospective analysis of all patients undergoing ICP monitoring at a designated paediatric neurosurgical and craniofacial unit in the United Kingdom between October 2009 and October 2018. The fundoscopy findings and ICP monitoring data were analysed for 31 children with craniosynostosis and 29 children without craniosynostosis. RESULTS: All children who had papilloedema had raised ICP confirmed with monitoring. Across the 60-patient cohort, confirmed papilloedema on fundoscopy had Positive Predictive Value (PPV) of 1.00, Negative Predictive Value (NPV) of 0.64 with sensitivity 48% and specificity 100% for the presence of raised ICP (p = < 0.0001). In the craniosynostosis group, PPV was 1.00, NPV was 0.39, sensitivity 48% and specificity 100% (p = < 0.03). There is no correlation between severity of optic disc swelling using Frisen grading and elevation of ICP. Age did not affect the presence of papilloedema in those with raised ICP. CONCLUSION: The presence of papilloedema is a strong indicator of raised ICP in a child, regardless of underlying aetiology. Detailed fundoscopy can prevent the need for further investigations including imaging-related radiation and invasive CSF pressure monitoring.

Optic Nerve Germinoma and Transient Spontaneous Regression-More Than Meets the Eye.

Infiltration of the optic pathway by germ cell tumors is exceptional and can lead to confusion with glioma or inflammatory conditions. We present the case of a 14-year-old girl with an optic nerve germinoma extending to the hypothalamus and manifesting as panhypopituitarism and visual loss. The patient experienced spontaneous regression of the lesion followed by secondary deterioration requiring treatment. Four other cases of spontaneously regressing intracranial germinoma followed by regrowth have been reported in the literature. This report highlights the importance of clinical and radiologic monitoring of intracranial germinoma, even in the event of initial spontaneous improvement.

Neurofibromatosis Type 2-Related Eye Disease Correlated With Genetic Severity Type.

OBJECTIVE: Neurofibromatosis type 2 (NF2) is an uncommon but well-recognized disorder characterized by multiple schwannomas and meningiomas. Adults typically present with hearing loss and balance disturbance, and children with ocular, dermatological, and neurological signs. Clinical diagnosis is confirmed by neuroimaging and genetic testing. Although ophthalmic features are present in patients with NF2, there are no reports correlating genetic severity subtypes with ophthalmic involvement. METHODS: We retrospectively reviewed longitudinal ophthalmological data of 83 patients with NF2, with known genetic severity subtype, to determine visual function over time. We created a scoring system (Oxford NF2 Ophthalmic Score [ONOS]) to quantify visually debilitating pathology. RESULTS: The prevalence of optic atrophy, combined hamartomas, cataract, and epiretinal membranes significantly increased with genetic severity. Median age of survival to visual acuity worse than 1.0 logarithm of minimum angle of resolution in one eye significantly decreased with genetic severity and was 38 years in the genetically severe group, 49 years in moderate classics, 64 years in mild classics, and 84 years in the tissue mosaics. In the genetically severe, the visually damaging pathologies were largely untreatable. The ONOS correlated with genetic severity longitudinally and cross-sectionally. CONCLUSIONS: Mutations associated with severe systemic disease result in greater visual morbidity at an earlier age. Those with tissue mosaicism are unlikely to have visually debilitating pathology secondary to NF2. Potentially treatable sources of damage to vision, however, affect all groups and must be identified early and treated effectively to retain useful vision throughout life.

Genetic Severity Score predicts clinical phenotype in NF2.

​BACKGROUND: The clinical severity of disease in neurofibromatosis type 2 (NF2) is variable. Patients affected with a constitutional truncating NF2 mutation have severe disease, while missense mutations or mosaic mutations present with a milder attenuated phenotype. Genotype-derived natural history data are important to inform discussions on prognosis and management. METHODS: We have assessed NF2 clinical phenotype in 142 patients in relation to the UK NF2 Genetic Severity Score to validate its use as a clinical and research tool. RESULTS: The Genetic Severity Score showed significant correlations across 10 measures, including mean age at diagnosis, proportion of patients with bilateral vestibular schwannomas, presence of intracranial meningioma, spinal meningioma and spinal schwannoma, NF2 eye features, hearing grade, age at first radiotherapy, age at first surgery and age starting bevacizumab. In addition there was moderate but significant correlation with age at loss of useful hearing, and weak but significant correlations for mean age at death, quality of life, last optimum Speech Discrimination Score and total number of major interventions. Patients with severe disease presented at a younger age had a higher disease burden and greater requirement of intervention than patients with mild and moderate disease. CONCLUSIONS: This study validates the UK NF2 Genetic Severity Score to stratify patients with NF2 for both clinical use and natural history studies.

Isolated extraocular muscle infiltration with plasmacytoma treated with localized injection of dexamethasone.

Plasmacytoma of the orbit secondary to multiple myeloma is rare and has not previously been reported limited to an extraocular muscle. Conventional treatment is either localized radiotherapy or systemic chemotherapy. We report a case of plasmacytoma within the medial rectus muscle, which regressed completely with localized infiltration of dexamethasone.

Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor.

Herpesvirus Saimiri gene 13 (HVS13) exhibits 57% identity with the predicted sequence of a T cell-derived molecule termed CTLA8. Recombinant HVS13 and CTLA8 stimulate transcriptional factor NF-kappaB activity and Interleukin-6 (IL-6) secretion in fibroblasts, and costimulate T cell proliferation. An HVS13.Fc fusion protein was used to isolate a cDNA encoding a novel receptor that also binds CTLA8. This receptor is unrelated to previously identified cytokine receptor families. A recombinant soluble receptor inhibited T cell proliferation and IL-2 production induced by PHA, concanavalin A (conA), and anti-TCR MAb. These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vIL-17, and IL-17R, respectively.

Diagnostic Accuracy of Online Visual Acuity Testing of Paediatric Patients.

Background/Objectives: Remote assessment of children's visual acuity became necessary during the COVID-19 pandemic. This study aimed to assess the extent of agreement between hospital-based clinical testing and clinician-led home-based testing. Subjects/Methods: 50 children aged 2-16 (median 8) years attending hospital eye services at two UK hospitals had routine hospital-based acuities compared with subsequent online, orthoptist-supervised home visual acuities. Agreement was assessed using intra-class correlation and Bland-Altman plots, as was test-retest (TRT) agreement of two, repeated home acuity tests. Results: Monocular acuities tested at hospital and at home were obtained from all 50 children; 33 also had binocular acuities in both settings and 35 had acuities retested immediately at home. Most children were tested at home using a computer or tablet; two were tested with a smartphone. No mean test differences were found for hospital vs home testing (-0.004 (95% CI -0.06-0.05) and -0.008 (95% CI -0.04-0.03) for binocular and monocular testing, respectively). Limits of agreement (LOAs) were ±0.32 and ±0.35 logMAR for binocular and monocular testing, respectively. LOAs for inter-ocular acuity differences (hospital vs home) were -0.15-0.25 logMAR. TRT monocular acuity agreement was excellent, with an LOA of ±0.14 logMAR. Conclusions: We found good (binocular) and excellent (monocular) agreement between hospital and home acuity testing. LOAs were in keeping with multiple changes between measures (test; setting; time; tester) and a cohort including patients as young as two years old. Even smartphone testing proved feasible. Inability of the supervising orthoptist to check test distance or device calibration/orientation was a limitation, likely contributing to the breadth of LOAs. Home vision testing is feasible and accurate, but its precision, acceptability, health economic impact and carbon impact require more attention.

Ophthalmological Care of Patients With Craniofacial Disorders.

Patients presenting with craniofacial conditions present a unique challenge from an ophthalmological view point. There are no set guidelines as to their management or their long-term monitoring and follow-up. Largely, this should be the remit of a dedicated craniofacial team. Here we present pertinent ophthalmological pathology occurring in combination with craniosynostosis alongside the protocol employed in Birmingham Children's Hospital for the management of these patients.

Outcomes following tacrolimus systemic immunosuppression for penetrating keratoplasty in infants and young children.

OBJECTIVE: To report outcomes of tacrolimus immunosuppression after penetrating keratoplasty (PK) in very young children. METHODS: Retrospective, consecutive, cohort study of children undergoing PK at a tertiary children's hospital between 2005 and 2016. Oral tacrolimus immunosuppression was given for 2 years, followed by topical tacrolimus. RESULTS: Fourteen children (20 eyes) had 24 PKs; nineteen eyes had primary PKs, five eyes had repeat PKs. Mean age at primary graft was 95 days (3.1 months) for anterior segment dysgenesis (ASD), 430 days (14.3 months) for non-ASD children. Eleven children (15 eyes) had ASD. Three children (five eyes) had non-ASD: two children (three eyes) had glaucoma-related corneal opacity and one child (two eyes) had congenital hereditary endothelial dystrophy (CHED). One-year rejection-free survival rates following primary PK was 80% for ASD (n = 15) and 100% for non-ASD (n = 4). At final review, 5/15 of primary grafts for ASD were clear. 10/15 failed after a mean of 19 months, specifically attributable to infection (n = 2), rejection (n = 2) and glaucoma (n = 2). 4/4 primary non-ASD grafts are clear at final review (mean follow-up = 77 months). All repeat grafts (n = 5), failed after a mean of 38.25 months. Considering all grafts, 15/24 (62.5%) failed: 5/15 due to infection, 2/15 due to rejection, 8/15 due to glaucoma, phthisis, perforation or vascularised with no rejection. At last review (mean = 58.1 months, range 28-84), overall cohort survival is 37.5%. Final visual acuities range between 0.86 and 2.4 LogMAR. CONCLUSION: We compare our results to published literature: 1-year graft survival was higher than previously reported, with lower failure due to rejection. Overall infection rates did not increase, however, proportionally, severe infections were higher. Overall graft survival is at least comparable to reported literature.

Parental Home Vision Testing of Children During Covid-19 Pandemic.

BACKGROUND: The Covid-19 pandemic necessitated social distancing restrictions, which placed limitations on access to ophthalmic care to only those who had an imminent risk of sight loss. All other face-to-face consultations were converted to telephone consultations or were postponed. We investigated whether parents were able to test their child's vision using available home vision testing applications, with an aim to aid decision making during a telephone consultation. METHODS: Families with follow-up consultations at Birmingham Children's Hospital were asked to test their child's vision at home. Instructions for the use of Peek acuity, or iSight Pro, were emailed to a parent. Parents chose to use a particular app based on available devices at home. Parents were asked to test uniocular visual acuity twice. Home versus hospital acuity was correlated. Home acuity test-retest reliability was acquired. Parental feedback was obtained through questionnaires. RESULTS: One hundred and three families were contacted, 15 families completed home vision testing. Ten families used Peek acuity, five families used iSight Pro. Uniocular visual acuity test-retest reliability was 0.03 LogMAR. Home-hospital acuity testing had a bias of 0.14 LogMAR, hospital acuity yielding a lower LogMAR score. Most families who completed testing found it easy to do; however, some struggled, and 81 families did not undertake home vision testing. CONCLUSIONS: Uptake of home vision testing was limited by parental engagement, most likely influenced by the current pandemic. Most families who undertook home vision testing were able to generate results that could be used for clinical decision making. Extending the impact of parental vision testing will require education by clinicians and further study to increase sample sizes and to improve confidence.

Disability and visual outcomes following suspected abusive head trauma in children under 2 years.

AIM: To report disability and visual outcomes following suspected abusive head trauma (AHT) in children under 2 years. METHODS: We present a retrospective case series (1995-2017) of children with suspected AHT aged ≤24 months. King's Outcome Score of Childhood Head Injury (KOSCHI) was used to assess disability outcomes at hospital discharge and at follow-up. The study used a retinal haemorrhage score (RHS) to record findings at presentation and a visual outcome score at follow-up. RESULTS: We included 44 children (median age 16 weeks). At presentation, 98% had a subdural haemorrhage and 93% had a retinal haemorrhage. At discharge, 61% had moderate-to-severe disability, and 34% a good recovery. A higher RHS was observed in those with more disability (r=-0.54, p=0.0002). At follow-up, 14% had a worse KOSCHI score (p=0.055). 35% children had visual impairment, including 9% with no functional vision. Those with poorer visual function had a higher RHS (r=0.53, p=0.003). 28% attended mainstream school without support; 50% were in foster care or had been adopted, 32% lived with birth mother and 18% with extended family. CONCLUSION: It is known that injuries from suspected AHT result in high levels of morbidity; our cohort showed significant rates of disability and visual impairment. Those with higher disability at discharge and poorer visual function showed more significant retinal changes. The extent of disability was not always apparent at hospital discharge, impacting on provision of prognostic information and targeted follow-up.

Optic neuropathy in superficial intracranial siderosis.

Superficial intracranial siderosis is a degenerative condition secondary to recurrent occult subarachnoid hemorrhage. Progressive sensorineural deafness, cerebellar ataxia, and pyramidal signs are well-documented clinical manifestations, but optic neuropathy is not a recognized feature. We describe 2 patients with clinical and electrophysiological evidence of optic nerve/chiasm dysfunction and MRI signal abnormalities consistent with hemosiderin staining of the anterior visual pathway. In a third case, neuropathological examination of the optic chiasm showed demyelination attributed to hemosiderin deposition. We suggest that anterior visual pathway damage may be underrecognized in this condition.

Professional Society Ethics Group exchanges experience.

KIE: A brief report is given of the October 1984 semiannual meeting of the Professional Society Ethics Group, which comprises 26 societies affiliated with the American Association for the Advancement of Science. At the meeting, a representative of the American College of Physicians (ACP) discussed a new ACP Ethics Manual written by an ad hoc committee of the ACP to address major ethical issues encountered by physicians in daily practice, and a representative of the American Psychological Association (APA) described the investigative and adjudication procedures used by the APA for handling ethics complaints.^ieng

Professional ethics group reviews guidelines for misconduct investigations.

KIE: Many scientific societies have begun to re-examine their standards of conduct and procedures for investigating alleged misconduct by members in light of recent litigation involving professional codes of ethics and an increase in reported incidences of misconduct by academic researchers. Painter summarizes a Spring 1984 meeting of the American Association for the Advancement of Science Professional Ethics Group, at which speakers outlined general guidelines for revising professional codes and for investigating complaints against members. Among the issues discussed were confidentiality, institutional obligations to inform third parties of investigations, due process requirements, professional liability insurance, and professional duties to the public.^ieng

Lens reabsorption following self-induced needling and subsequent intracapsular secondary intraocular lens placement.

We present the case of a young man who inadvertently penetrated his cornea and lens with a needle used for injecting heroin. Three years later, the lens had completely reabsorbed leaving a fibrosed capsular bag. We describe the surgical techniques used to insert a secondary intraocular lens into the capsular bag with excellent visual outcome.

Möbius syndrome associated with obesity and precocious puberty.

Möbius syndrome is a neurological disorder involving underdevelopment of the sixth and seventh cranial nerves. Multiple associations have been described including dysfunction of other cranial nerves, limb abnormalities and hypogonadotrophic hypogonadism causing delayed puberty. We present the second reported case of Möbius syndrome associated with obesity and with precocious puberty. These features may be secondary to dysregulation of the hypothalamic-pituitary axis. We highlight the need to consider extraocular symptoms in these patients and for close liaison with physicians in their management.

Topical timolol maleate 0.5% solution for the management of deep periocular infantile hemangiomas.

This retrospective, consecutive, clinical case series examined the use of topical timolol in the treatment of 5 children with deep, periocular infantile hemangiomas that caused astigmatism, change in head posture, or ptosis. All patients were treated with timolol maleate solution 0.5% twice daily until the lesions had regressed. All 5 children showed regression of the lesion and improvement in amblyogenic risk factors within 2 weeks.

Review of topical beta blockers as treatment for infantile hemangiomas.

The treatment of infantile hemangiomas changed from the use of oral corticosteroids to oral propranolol on the serendipitous discovery of propanolol's clinical effectiveness in 2008. Since then, clinicians have begun to use topical beta blockers--in particular, timolol maleate 0.5% gel forming solution--with good effect. Topical beta blockers are now used for lesions with both deep and superficial components and those that are amblyogenic. When initiated in the proliferative phase of the lesion, the effectiveness of the treatment can be seen within days. There is no consensus on dosing, treatment bioavailability, or clinical assessment of lesions, but these are topics for future research.

Incidence and treatment of retinopathy of prematurity in England between 1990 and 2011: database study.

AIMS: To study the incidence and treatment of retinopathy of prematurity (ROP) in England, 1990-2011. METHODS: English national Hospital Episode Statistics were analysed, for babies born in hospital and for inpatient admissions, to obtain annual rates of diagnosis of, and treatment for, babies with ROP. National data on low birthweight (LBW) babies, born <1500 g and therefore eligible for ROP screening, were used as denominators in calculating rates of ROP per 1000 babies at risk. RESULTS: The recorded incidence of ROP increased tenfold, from 12.8 per 1000 LBW babies in 1990 to 125.5 per 1000 LBW babies in 2011. Tretment rates for ROP by cryotherapy or laser rose from 1.7 to 14.8 per 1000 LBW babies between 1990 and 2011. In 1990, 13.3% of babies with ROP were treated with cryotherapy, which fell to 0.1% in 2011. Rates for laser treatment rose from 1.8% of babies with ROP in 1999 to 11.7% in 2011. CONCLUSIONS: Increased neonatal survival, improved awareness of ROP and dissemination of guidance on screening and treatment of ROP will all have contributed to the substantial rise in recorded incidence of ROP between 1990 and 2011. Retinal ablation is now almost always performed using laser treatment rather than cryotherapy.