Jane Gardiner

Ophthalmic complications of otitis media in children

PURPOSE To evaluate the outcome of ophthalmic complications in children with otitis media. METHODS The records of children with ophthalmic complications arising from otitis media who presented to the British Columbia Childrens Hospital between August 2006 and March 2008 were reviewed retrospectively. RESULTS Of 1,400 patients presenting to the emergency department for otitis media during the study period, 7 with ophthalmic complications were identified (age range, 1-11 years). All patients had abducens nerve palsy on presentation. Other notable ophthalmic complications included papilledema, Horner syndrome, and proptosis. Extracranial and intracranial complications included mastoiditis, petrositis, parapharyngeal abscess, hydrocephalus, epidural abscess, and cerebral venous thrombosis, including cavernous sinus thrombosis in 2. Of the 7 patients, 6 were treated with surgery, including myringotomy and tube placement (6 patients) and mastoidectomy (3 patients). All patients were initially anticoagulated and received intravenous antibiotics. Satisfactory final visual outcomes and stereopsis ranging from 40 to 100 seconds were achieved in all patients. CONCLUSIONS Ophthalmic complications of otitis media in children are likely to include abducens palsy. All patients in our series required anticoagulation and intravenous antibiotics. Most required otolaryngologic surgery, but none required strabismus surgery, and all patients had satisfactory visual and ocular motility outcomes.

Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment

Objective To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months’ corrected age (CA) compared with neonates without severe ROP. Design We conducted a prospective longitudinal cohort of extremely preterm neonates born 24–28 weeks’ gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months’ CA. Subjects were compared using Fisher’s exact, Kruskal-Wallis and generalised estimating equations. Setting Families were recruited from the neonatal intensive care unit at BC Women’s Hospital. Patients Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months’ CA. Results Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP. Conclusions Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months’ CA.

A variant of unknown significance in the GLA gene causing diagnostic uncertainty in a young female with isolated hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous, and largely caused by mutations in genes encoding sarcomere proteins. However, GLA mutations causing Fabry disease, an X-linked lysosomal storage disorder, may also present with isolated HCM. As HCM genetic testing panels are increasingly being used clinically, variants of unknown significance (VUS) are encountered, leading to challenges in interpretation. We present an illustrative case: a 10-year-old girl with isolated HCM who, on testing with a HCM multi-gene panel, was found to carry a maternally inherited p.W24R variant in GLA. Attempts to evaluate the significance of this variant, by direct biochemical testing of patient specimens, gave inconclusive results. Subsequent in vitro protein expression studies suggested that the variant is unlikely to be pathogenic. This case highlights diagnostic dilemmas that can be provoked by VUS in general, and specifically raises a question whether GLA sequencing should be included in first-line diagnostic testing for female children with isolated hypertrophic cardiomyopathy.

The effect of changing oxygen saturation protocols on the incidence of laser treatment for retinopathy of prematurity

OBJECTIVE To compare the incidence of retinopathy of prematurity (ROP) requiring laser treatment among infants with birth weights of ≤ 1250 g before and after the implementation of a new oxygen saturation protocol in the neonatal intensive care unit of British Columbia Childrens Hospital. DESIGN Retrospective, comparative review of medical records. PARTICIPANTS Premature infants with birth weights of ≤ 1250 g who were screened for retinopathy of prematurity from November 2003 to October 2005 and February 2006 to January 2008 (269 patients). METHODS The hospitals ROP database was reviewed, and the patients were divided into 2 groups. The preprotocol group (November 2003-October 2005) consisted of patients who were screened before the new oxygen monitoring protocol was instituted and the postprotocol group (February 2006-January 2008) consisted of patients screened after its implementation. RESULTS A total of 141 patients were in the preprotocol group and 128 patients in the postprotocol group. The mean birth weight and gestational age of the 2 groups were comparable (p = 0.81, 0.71, respectively). There was a 30% reduction in the incidence of laser treatment in the postprotocol group (preprotocol group = 22/141 [15.6%] vs postprotocol group = 13/128 [10.2%]; p = 0.19). CONCLUSIONS We observed a decrease in the rate of severe ROP requiring laser treatment after the implementation of the new oxygen monitoring protocol. While not statistically significant, this is consistent with what has been found at other centres.

Retinal hemorrhages requiring vitrectomy in a patient with hemophagocytic lymphohistiocytosis

To the Editor: Rare cases of ocular findings have been reported with hemophagocytic lymphohistiocytosis (HLH) [1–4]. We report a 7-year-old patient with Epstein-Barr virus (EBV)-associated HLH with subhyaloid hemorrhages requiring bilateral vitrectomies. HLH is a rare and sometimes life-threatening disorder in which macrophages are activated due to uncontrolled T-lymphocyte activation and pro-inflammatory signaling [1,5]. This activation may be due to infectious or other stimuli, or as a result of an inherited T-cell or natural killer cell defect (e.g. perforin deficiency), and may result in diffuse inflammation [6]. The classic syndrome of HLH includes fevers, hepatosplenomegaly and bicytopenia or pancytopenia. Only a few cases of retinal findings associated with HLH have been reported [1–4], including two patients with retinal hemorrhages [2,4]. A previously well patient presented with a 2-month history of fevers, rash, arthralgias and anorexia. She was pancytopenic with marked hepatosplenomegaly. A bone marrow aspirate and biopsy showed extensive hemophagocytosis. Biochemical studies were supportive of the diagnosis of HLH: lactate dehydrogenase >20,000 U/L; triglyceride level 8.48 mmol/L; peak ferritin level 119,000 mg/L; fibrinogen level 3.06 g/L. She had no cerebral involvement. Active infection with EBV was documented by blood polymerase chain reaction (pcr) testing. Therapy was initiated as per the Histiocyte Society HLH-2004 protocol. No specific anti-EBV therapy was given after consultation with our Infectious Disease service. Genetic studies for familial HLH were negative. However, it is recognized that many cases of familial HLH are precipitated by infectious agents such as EBV [7]. At presentation, multiple subhyaloid hemorrhages were discovered with macular involvement. The optic discs were normal, with no vasculitis seen. Decreased visual acuity was documented bilaterally. Despite a response to treatment, continued ophthalmologic follow-up confirmed that the multiple subhyaloid hemorrhages were not clearing and were impairing her vision to 20/400 OD and 20/200 OS (Supplemental Fig. 1). Two months after diagnosis the child underwent vitrectomy, membrane peeling and hyaloid stripping of the right eye with air fluid exchange and endolaser application. Three weeks later the left eye required vitrectomy, air fluid exchange, membrane peeling and endolaser application. The patient’s vision improved to 20/20 in the right eye and 20/25þ in the left eye, uncorrected. Increased pressure in the right eye required prostaglandin analogue topical therapy, possibly due to subtenons steroids injected during a previous procedure. Unfortunately she relapsed with EBV reactivation while on continuation therapy. This unusual reactivation may have been due to immunosuppressive therapy. As previously noted, no anti-EBV therapy had been given initially. Re-induction chemotherapy was given as per HLH-2004 in addition to ganciclovir and rituximab, and she subsequently underwent an unrelated donor 5/6 antigen match cord blood stem cell transplant. Full donor engraftment was achieved, but the patient developed multi-organ failure due to transplant-related toxicity. She died on day þ56, autopsy was declined. Reports of ocular findings in HLH are rare [1–4]. However, we suggest careful ophthalmologic examination in all patients with HLH as eye findings may warrant close monitoring and intervention to preserve vision.

Painful Acute Corneal Ulceration and Anterior Stromal Keratitis in an Adolescent With Reactive Arthritis

Reactive arthritis is occasionally associated with conjunctivitis and uveitis, but rarely keratitis. The authors describe a patient with paracentral anterior stromal keratitis with overlying epithelial erosion and multiple satellite subepithelial infiltrates. The initial appearance and the severe pain were suggestive of an infectious process. Recovery was rapid following introduction of topical steroid, with features suggesting an immune process in the recovery phase. The authors suggest that a history of arthritis and/or recent enteritis should be sought in the work-up of an atypical keratitis with or without epithelial defect. [J Pediatr Ophthalmol Strabismus. 2016;53:e61-e63.].