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.

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.

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.

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.

[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.

Antidepressant switching patterns in the treatment of major depressive disorder: a General Practice Research Database (GPRD) Study.

AIMS: To investigate switching patterns of major antidepressant treatments and associated factors in a primary care adult population with major depressive disorder (MDD) using data from the General Practitioner Research Database (GPRD). METHODS: A retrospective cohort study was conducted using the GPRD. The study included patients with MDD, aged [18-70], with a new prescription for amitriptyline, citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine between January 1, 2001 and September 30, 2003 and having no antidepressant prescription in the 6 months preceding index date. Switching of antidepressant treatment was defined as a prescription of a different antidepressant among all available marketed antidepressant treatment at this time (no restriction of compound) from 1 month before up to 2 months after the calculated end of the previous antidepressant treatment. Survival analysis techniques were used to describe switching of antidepressant and time to switch. Profiles of switchers were described and by-treatment analyses performed. RESULTS: Data from over 59,000 patients showed that 16% switched antidepressants. Seventy-two per cent of switches appeared within 3 months after treatment initiation. Within switchers, median time to switch was 53 days. Switching patients had generally a more severe psychiatric profile, including more previous episodes of depression or other psychiatric disorders. They also had a higher proportion of concurrent psychiatric disorders (especially anxiety) and concomitant prescription of anxiolytics or hypnotics. Patients initially prescribed amitriptyline were almost twice as likely to switch (27%) as patients prescribed venlafaxine (17%) or an SSRI (15%). CONCLUSIONS: This population-based study confirmed that antidepressant switch is more likely to occur within the first 3 months of treatment and in patients with a more severe psychiatric profile. A particular attention paid to these patients within the early phase of treatment may therefore help to improve their management.

[Hereditary optic neuropathies]. / Neuropathies optiques héréditaires.

Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized.

[Is it optic neuritis? Differential diagnosis]. / Névrite optique. Diagnostics différentiels.

Optic neuritis is clinically suspected when painful, rapidly progressive central visual loss occurs in a young patient who has a relative afferent pupillary defect. Ophthalmoscopy is normal in the majority of cases but papillitis or optic disc palor can occur. Several other diseases can mimic optic neuritis, such as ophthalmological conditions or other diseases affecting the visual pathways. Their appropriate clinical diagnosis is of paramount importance in order to avoid unnecessary or invasive procedures or treatments.

[Optic disc drusen or true papilledema?]. / Drusen de la tête du nerf optique ou oedème papillaire?

INTRODUCTION: Bilateral optic disc drusen can mimic papilledema, raising the question of intracranial hypertension and sometimes prompting unnecessary or invasive procedures. STATE OF THE ART AND PERSPECTIVES: Optic disc drusen are benign calcified masses, often visible within the optic nerve head. However, their clinical diagnosis can be more difficult at earlier stages of life, when they are buried within the optic nerve. Visual field loss can occur in patients with longstanding optic disc drusen. CONCLUSION: Ophthalmoscopy and B-scan ocular ultrasonography allow appropriate diagnosis of bilateral optic disc drusen mimicking papilledema. On rare occasions, optic disc drusen can be associated with ischemic complications, the other causes of drusen-related visual loss being exceptionally rare.

Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts.

Mitochondria are dynamic organelles with continuous fusion and fission, the equilibrium of which results in mitochondrial morphology. Evidence points to there being an intricate relationship between mitochondrial dynamics and oxidative phosphorylation. We investigated the bioenergetics modulation of mitochondrial morphology in five control cultured primary skin fibroblasts and seven with genetic alterations of oxidative phosphorylation. Under basal conditions, control fibroblasts had essentially filamentous mitochondria. Oxidative phosphorylation inhibition with drugs targeting complex I, III, IV or V induced partial but significant mitochondrial fragmentation, whereas dissipation of mitochondrial membrane potential (D Psi m) provoked complete fragmentation, and glycolysis inhibition had no effect. Oxidative phosphorylation defective fibroblasts had essentially normal filamentous mitochondria under basal conditions, although when challenged some of them presented with mild alteration of fission or fusion efficacy. Severely defective cells disclosed complete mitochondrial fragmentation under glycolysis inhibition. In conclusion, mitochondrial morphology is modulated by D Psi m but loosely linked to mitochondrial oxidative phosphorylation. Its alteration by glycolysis inhibition points to a severe oxidative phosphorylation defect.

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.