Personalized diagnosis and management of congenital cataract by next-generation sequencing.

PURPOSE: To assess the utility of integrating genomic data from next-generation sequencing and phenotypic data to enhance the diagnosis of bilateral congenital cataract (CC). DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: Thirty-six individuals diagnosed with nonsyndromic or syndromic bilateral congenital cataract were selected for investigation through a single ophthalmic genetics clinic. METHODS: Participants underwent a detailed ophthalmic examination, accompanied by dysmorphology assessment where appropriate. Lenticular, ocular, and systemic phenotypes were recorded. Mutations were detected using a custom-designed target enrichment that permitted parallel analysis of 115 genes associated with CC by high-throughput, next-generation DNA sequencing (NGS). Thirty-six patients and a known positive control were tested. Suspected pathogenic variants were confirmed by bidirectional Sanger sequencing in relevant probands and other affected family members. MAIN OUTCOME MEASURES: Molecular genetic results and details of clinical phenotypes were identified. RESULTS: Next-generation DNA sequencing technologies are able to determine the precise genetic cause of CC in 75% of individuals, and 85% patients with nonsyndromic CC were found to have likely pathogenic mutations, all of which occurred in highly conserved domains known to be vital for normal protein function. The pick-up rate in patients with syndromic CC also was high, with 63% having potential disease-causing mutations. CONCLUSIONS: This analysis demonstrates the clinical utility of this test, providing examples where it altered clinical management, directed care pathways, and enabled more accurate genetic counseling. This comprehensive screen will extend access to genetic testing and lead to improved diagnostic and management outcomes through a stratified medicine approach. Establishing more robust genotype-phenotype correlations will advance knowledge of cataract-forming mechanisms.

Post-vaccination encephalomyelitis: literature review and illustrative case.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that is usually considered a monophasic disease. ADEM forms one of several categories of primary inflammatory demyelinating disorders of the central nervous system including multiple sclerosis, optic neuropathy, acute transverse myelitis, and neuromyelitis optica (Devic's disease). Post-infectious and post-immunisation encephalomyelitis make up about three-quarters of cases, where the timing of a febrile event is associated with the onset of neurological disease. Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. We performed a literature search using Medline (1976-2007) with search terms including "ADEM", "acute disseminated encephalomyelitis", "encephalomyelitis", "vaccination", and "immunisation". A patient presenting with bilateral optic neuropathies within 3 weeks of "inactivated" influenza vaccination followed by delayed onset of ADEM 3 months post-vaccination is described.

Craniofacial linear scleroderma associated with retinal telangiectasia and exudative retinal detachment.

Linear scleroderma is a characteristic form of scleroderma that typically affects children. Ocular manifestations may be present, especially when the frontoparietal area of the head is affected. We present the case of a 5-year-old boy with craniofacial linear scleroderma ("en coup de sabre") who developed exudative retinal detachment. Angiographic and neuroimaging findings are presented, and the importance of regular fundus examination is highlighted.

Spectrum of clear corneal incision cataract wound infection.

PURPOSE: To describe the presentation, management, and outcome of 5 patients who presented with main-port or side-port wound infection after uneventful clear corneal cataract surgery. SETTING: Ophthalmic Surgery Centre, Chatswood, and Department of Ophthalmology, Prince of Wales Hospital, Randwick, Australia, and Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. METHODS: This retrospective case series comprised 5 patients who had uneventful clear corneal phacoemulsification surgery and developed either a main-port or side-port wound infection. The clinical features, microbiologic studies, management, and results are reported. RESULTS: The median age of the patients was 79 years. Infection of the main-port incision occurred in 3 cases and of the side port in 2 cases. The patients presented from a few days to several weeks after uneventful phacoemulsification. In 2 cases, the bacteria Pseudomonas aeruginosa and Staphylococcus aureus were isolated. In 1 case, the fungus Aspergillus was isolated and required extensive medical and surgical treatment. In the other 2 cases; empiric antimicrobial therapy was given because no organism was isolated in 1 case, and in the other milder case, microbiological investigations were not performed. Final visual acuity was 6/4 in 2 cases and 6/5, 6/12, and 6/18 in 1 case each. CONCLUSIONS: Bacterial or fungal wound infection can present within days or even several weeks following clear corneal cataract surgery. Patients with ocular discomfort or blurred vision after such surgery should be advised to report promptly. Rapid identification and appropriate management of patients with clear corneal wound infection can result in good visual outcomes.

Endovascular treatment of an acute left middle cerebral artery >6 h post stroke in a patient presenting with dysphasia and dense right hemiplegia.

This paper describes the case of a 32-year-old man presenting with dense right hemiplegia and global aphasia caused by an acute left middle cerebral artery infarct that underwent successful endovascular therapy after being determined ineligible for intravenous tissue plasminogen activator. Clot transversion and balloon disruption followed by intra-arterial Alteplase resulted in successful re-canalization of his middle cerebral artery at 7 h 30 min. At 3 months post stroke, the patient had moderately severe expressive dysphasia but was mobilizing independently with normal right upper and lower limb strength. In conclusion, the 3 month outcome suggests that the therapeutic time window for endovascular therapy might exceed 6 h post stroke.

Outcomes of patients with transient ischaemic attack after hospital admission or discharge from the emergency department.

OBJECTIVE: To compare outcomes at 28 days and 1 year between patients admitted to hospital and those discharged after presenting to the emergency department (ED) with transient ischaemic attack (TIA). DESIGN AND SETTING: All TIA presentations to EDs in a large metropolitan and rural region of Sydney and its surroundings, New South Wales, between 2001 and 2005 were extracted from state health department databases and followed up over 1 year. Admission and discharge data and subsequent TIA or stroke presentations were identified. MAIN OUTCOME MEASURES: TIA recurrence or stroke. RESULTS: Of 2535 presentations to an ED with TIA during the 5-year period, 1816 patients were admitted to hospital (71.6%) and 719 were discharged from the ED (28.4%). At 28 days, the discharged group had significantly higher rates of recurrence than the admitted group for all events (TIA or stroke) (5.3% v 2.3%, P < 0.001), stroke (2.1% v 0.7%, P = 0.002), and recurrent TIA (3.2% v 1.6%, P = 0.01). During the 29-365-day follow-up period, there was no significant difference between the discharged and admitted groups for all events (4.2% v 5.1%; P = 0.37), stroke (1.3% v 2.5%; P = 0.06) or recurrent TIA (2.9% v 2.6%; P = 0.65). CONCLUSION: Patients with an ED diagnosis of TIA may benefit from admission to hospital through a reduced risk of early stroke.