Too Young to Undergo Temporal Artery Biopsy? Calciphylaxis-Related Anterior Ischemic Optic Neuropathy.

A 39-year-old male patient with end-stage renal failure presented with unexplained isolated unilateral anterior ischemic optic neuropathy, high sedimentation rate, and high CRP. Despite the relatively young age of the patient, an ipsilateral temporal artery biopsy was performed, disclosing calciphylaxis, a highly morbid condition associated with end-stage renal failure, which requires urgent, specific management.

Subretinal fibrosis is associated with fundus pulverulentus in pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by mutations in the ABCC6 gene, resulting in various retinal lesions, among other systemic manifestations. Visual loss may occur in PXE, most commonly caused by choroidal neovascularization and macular atrophy, but little is known about the consequences of fundus pulverulentus (FP) in PXE. The aim of this study was to evaluate ophthalmic outcomes in patients with FP associated with PXE in a large series of PXE patients. METHODS: In a retrospective observational study, ophthalmic outcomes were compared between two groups of age-matched patients with genetically and pathologically confirmed PXE: one group with FP versus one without FP. All included patients underwent thorough clinical examination. Further investigation (optical coherence tomography (OCT), Cirrhus, Zeiss Germany, and/or fluorescein/indocyanin green angiography) was performed in cases of suspected choroidal neovascularization (CNV). RESULTS: The study included 13 PXE patients with FP (group 1: 8 men and 5 women, aged 45-65 years) and 47 age-matched PXE patients without FP (group 2: 19 men and 28 women). Mean patient follow-up was 63 months (range 0-132 months). Subretinal fibrosis (SRF) was more frequently associated with FP (9/26 eyes, 34.6%), compared to absence of FP (4/94, 4.2%) (p = 0.0001). Independently of SRF, FP can evolve into deep macular atrophy and/or CNV with dramatic consequences for central vision. CONCLUSIONS: Fundus pulverulentus may occur in PXE and is most commonly associated with subretinal fibrosis in the posterior pole and visual loss by macular atrophy even in the absence of CNV.

An overview of the clinical applications of optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.

Multiethnic involvement in autosomal-dominant optic atrophy in Singapore.

PurposeAutosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore.Patients and methodsPreliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene.ResultsAmong 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA.ConclusionWe report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing 'ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.

[Neuro-ophthalmic emergencies]. / Urgences en neuro-ophtalmologie.

Neuro-ophthalmic emergencies can cause life-threatening or sight-threatening complications. Various conditions may have acute neuro-ophthalmic manifestations, including inflammatory or ischemic processes, as well as tumoral, aneurysmal compression or metabolic and systemic diseases. Diplopia related to a partial third nerve palsy with pupillary involvement may reveal an intracranial aneurysm. Abnormalities of conjugate gaze may reveal an inflammatory or ischemic lesion, most often of the brainstem. An intracranial tumor may also manifest itself as a single or multiple oculomotor palsy, or causing various visual field defects, due to optic nerve, chiasm or retrochiasmal involvement. Arteritic anterior ischemic optic neuropathy may be the first manifestation of giant cell arteritis, prompting rapid treatment with steroids to prevent contralateral involvement. A (painful) Horner syndrome may be the presenting sign of carotid dissection, or it may be a sign of a central or thoracic sympathetic lesion. Beyond these classical emergencies, this non-exhaustive review will also present more rare clinical situations, describing novel algorithms for quick recognition and prompt intervention in acute neuro-ophthalmology.

Vitamin D insufficiency and cognitive impairment in Asians: a multi-ethnic population-based study and meta-analysis.

BACKGROUND: The relationship between vitamin D insufficiency and cognitive impairment remains equivocal in Asians. We examined the association between circulating 25-hydroxyvitamin D (25OHD) concentration and cognitive performance in a large multi-ethnic Singaporean population-based study. We also conducted a meta-analysis of 25OHD concentrations amongst cognitively impaired older adults in Asia. METHODS: Our population-based cross-sectional study included 2273 persons ≥60 years of age from the Singapore Epidemiology of Eye Diseases (SEED) study (mean ± SD age 70.4 ± 6.2 years; 44.7% female), who were categorized according to 25OHD concentration (i.e. ≤10, 10.1-20 and >20 ng mL(-1) ). The 25OHD concentration was measured and adjusted to reflect a deseasonalized value. Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Global cognitive impairment was defined as AMT score of ≤6 if 0-6 years of education and AMT score of ≤8 if >7 years of education. Fully adjusted multivariate models were used. We included seven studies in a meta-analysis of 25OHD and cognition in Asia (6068 participants; 1179 cognitively impaired cases). RESULTS: Participants with 25OHD levels >20 ng mL(-1) (n = 1302) had higher AMT total scores (mean ± SD 8.5 ± 1.9) and were less likely to have cognitive impairment (14.1%) than participants with lower 25OHD levels (overall P < 0.001, P-trend < 0.001). Deseasonalized 25OHD concentration was associated with AMT score (ß = 0.10 per 10 ng mL(-1) , P = 0.035). Vitamin D insufficiency (25OHD ≤20 ng mL(-1) ) was associated with global cognitive impairment (OR 1.56, P = 0.028). Specifically, 25OHD concentration correlated with semantic memory (r = 0.08, P = 0.009) and orientation in time (r = 0.09, P = 0.003). In the meta-analysis, the pooled mean 25OHD difference was -6.83 ng mL(-1) (95% confidence interval -11.36; -2.30), indicating lower 25OHD concentrations amongst cognitively impaired compared to cognitively healthy participants in Asia. CONCLUSION: Vitamin D insufficiency is associated with a greater likelihood of and more severe cognitive impairment in Asian populations.

Mitochondrial dysfunction affecting visual pathways.

Mitochondrial dysfunction leads to cellular energetic impairment, which may affect the visual pathways, from the retina to retrochiasmal structures. The most common mitochondrial optic neuropathies include Leber's hereditary optic neuropathy and autosomal dominant optic atrophy, but the optic nerve can be affected in other syndromic conditions, such as Wolfram syndrome and Friedreich's ataxia. These disorders may result from mutations in either the mitochondrial DNA or in the nuclear genes encoding mitochondrial proteins. Despite the inconstant genotype-phenotype correlations, a clinical classification of mitochondrial disorders may be made on the basis of distinct neuro-ophthalmic presentations such as optic neuropathy, pigmentary retinopathy and retrochiasmal visual loss. Although no curative treatments are available at present, recent advances throw new light on the pathophysiology of mitochondrial disorders. Current research raises hopes for novel treatment of hereditary optic neuropathies, particularly through the use of new drugs and mitochondrial gene therapy.

Ocular, bulbar, limb, and cardiopulmonary involvement in oculopharyngeal muscular dystrophy.

OBJECTIVES: To assess skeletal muscle weakness and progression as well as the cardiopulmonary involvement in oculopharyngeal muscular dystrophy (OPMD). MATERIALS AND METHODS: Cross-sectional study including symptomatic patients with genetically confirmed OPMD. Patients were assessed by medical history, ptosis, ophthalmoplegia, facial and limb strength, and swallowing capability. Cardiopulmonary function was evaluated using forced expiratory capacity in 1 s (FEV1), electrocardiogram (ECG), Holter monitoring, and echocardiography. RESULTS: We included 13 symptomatic patients (six males, mean age; 64 years (41-80) from 8 families. Ptosis was the first symptom in 8/13 patients followed by limb weakness in the remaining 5 patients Dysphagia was never the presenting symptom. At the time of examination, all affected patients had ptosis or had previously been operated for ptosis, while ophthalmoplegia was found in 9 patients. Dysphagia, tested by cold-water swallowing test, was abnormal in 9 patients (17-116 s, ref <8 s). Six patients could not climb stairs of whom two were wheelchair bound and one used a rollator. Six patients had reduced FEV1 (range 23%-59%). No cardiac involvement was identified. CONCLUSIONS: Limiting limb weakness is common in OPMD and can even be the presenting symptom of the disease. In contrast, dysphagia was not the initial symptom in any of our patients, although it was obligatory for diagnosing OPMD before genetic testing became available. Mild respiratory dysfunction, but no cardiac involvement, was detected.

[Systemic conditions associated with central and branch retinal artery occlusions]. / Apports du bilan étiologique des occlusions de l'artère centrale de la rétine et de ses branches et conséquences thérapeutiques.

INTRODUCTION: Retinal artery occlusions (RAO) are severe conditions threatening vision, affecting the subsequent mortality of these patients. PATIENTS AND METHODS: We retrospectively reviewed the work-up performed in all patients diagnosed with retinal artery occlusions evaluated in two university hospitals in France (Tours and Angers). RESULTS: A total of 131 patients (131 eyes) with RAO were included, with a mean age of 69.5years and male predominance (64 %). Central retinal artery occlusion (CRAO) resulted in poor initial visual acuity (90 % less than count fingers), whereas those with branch retinal artery occlusion (BRAO) had better visual acuity (63.6 % better than 20/40). Systemic arterial hypertension (HTN) was the most common associated risk factor. Carotid stenosis was found in 50 % of cases, leading to endarterectomy in nine patients (6.9 %), while an underlying cardiac cause was implicated in 14 % of cases. Giant cell arteritis was diagnosed in five patients (3.8 %). DISCUSSION: Work-up of RAO may detect treatable cardiovascular and systemic conditions, allowing prevention of further ocular recurrence or stroke. CONCLUSION: Etiologic work-up of retinal arterial occlusion can diagnose potentially treatable underlying systemic conditions, such as giant cell arteritis, cardiac conditions and extracranial cerebrovascular disease. Giant cell arteritis has to be ruled out at the acute phase, while the role and timing of semi-urgent testing (supra-aortic Doppler echography, echocardiography, electrocardiography, lab work-up) or delayed testing (transesophageal echocardiography, brain imaging) have yet to be determined.

[Orbital myositis associated with ipilimumab]. / Myosite orbitaire associée à un traitement par ipilimumab.

BACKGROUND: Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) that allows increased survival and, occasionally, complete remission, in the treatment of metastatic melanoma. The most frequent adverse effects are attributed to dysimmunity. We report the case of a female patient who developed orbital myositis during treatment with ipilimumab. PATIENTS AND METHODS: A woman on ipilimumab for a heel melanoma with mediastinal metastases was referred for evaluation of painful diplopia and proptosis that began three days after the fourth infusion of ipilimumab. The clinical examination disclosed a left abductiondeficit associated with conjunctival hyperaemia and palpebral oedema. Orbital MRI disclosed enlargement of the left lateral rectus, enhancing after contrast. An extensive work-up did not find any evidence for thyroid-related eye disease, as well as other orbital inflammatory processes, orbital cellulitis or orbital metastases. Treatment with high-dose oral steroids resulted in complete clinical recovery within a few days. DISCUSSION: To our knowledge, this is the first clinical report of orbital myositis as an adverse event related to anti-CTLA-4 antibody treatment. Both timing and usual profile of adverse events support the hypothesis that orbital myositis has to be attributed there to ipilimumab. Several dysimmune toxicities were observed with ipilimumab. Ophtalmic toxicity has unusually been described. Most cases were uveitis. Whether immune-related adverse events correlate with clinical response to ipilimumab treatment remains to be determined.