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Background : Classical MMA, caused by methylmalonyl-CoA mutase deficiency, may result in late-onset dysfunction in several organ systems. To date, 10 cases of optic neuropathy have been reported. The prevalence of optic neuropathy in visually asymptomatic patients has not been determined. This study sought to identify overt and subclinical optic neuropathy in a cohort with classical MMA. Methods and Materials : Neuroophthalmic examinations were performed on 21 patients identified with classical MMA, older than 10years. Diagnosis of optic neuropathy was determined by a combination of visual acuity, optic nerve appearance and electrodiagnostic tests. Tabulated data were analyzed for association of variables using SAS software. Significance was set at p < .05. Results : Two-thirds were Saudi nationals and one third, Syrian. Age range was 11-29years. Eleven (52.4%) patients had optic neuropathy. Nine (81.8%) of these were bilateral, seven (57.9% to 63.6%) reported decreased vision and four (33.1% to 36.4%) were asymptomatic. Two patients had catastrophic vision loss, following acute metabolic crises. Sixteen patients had chronic renal impairment while three had renal hypertension. Seventeen patients had short stature and eight, chronic pancreatitis. Methylmalonic acid levels ranged from 82 to 3,324µmol/L (Normal<1µmol/L). There was a significant association between optic neuropathy and female gender ( p = .011) and none with age, nationality, renal impairment, pancreatitis or specific genotype. Conclusion : Optic neuropathy was a frequent finding in classical MMA. It was often bilateral and some cases were sub-clinical, lacking visual symptoms. These findings have important management implications. Full ophthalmic evaluations should be performed early and regularly in patients with MMA, even when patients are asymptomatic.

Oxidative stress (OS) associated with direct contact with the environment and light exposure is a very potent and continuous stressor of the ocular surface and internal structures of the eye that are required to manage its effects. Constant replenishment of tears together with the superficial lipid layer produced by the meibomian glands (MG) is one protective mechanism. The lipid-rich fraction of the tears coats the deeper aqueous fraction, preventing its evaporation. However, lipids are particularly sensitive to oxidative damage that could alter tear film quality. To counteract oxidative damage, MG along with other structures of the ocular surface use primary antioxidant (AO) systems to limit OS damage such as lipid peroxidation. Limited information concerning the primary enzymatic AO system of the human MG prompted this investigation. Using different approaches (RT-PCR, enzymatic activity assays and immuno-fluorescent microscopy), we determined the presence, distribution and subcellular locations of the major AO enzymes belonging to the classical catalytic triad (superoxide dismutase, catalase and glutathione peroxidases) in adult human MG and conjunctiva (Conj). We showed that both tissues exhibit glutathione peroxidase expression. In addition to the ubiquitous cytosolic GPx1 protein, there was significant expression of GPx2, GPx4 and GPx7. These isoforms are known to preferentially scavenge phospholipid-hydroperoxide compounds. This characterization of the primary AO system of human MG and Conj may help pave the way for the development of diagnostic procedures and have implications for treatment of common MG dysfunction (MGD) and dry eye syndrome (DES)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To report a case of incidental asymptomatic atypical morning glory syndrome (MGS) with concomitant ipsilateral carotid and middle cerebral dysgenesis., Case Report: A 6-year-old child was discovered to have incidental findings of MGS, with atypia. All visual functions were normal including vision and stereopsis. Neuroimaging revealed ipsilateral carotid and middle cerebral vascular narrowing without associated collateral vessels or cerebral ischemia commonly seen in Moyamoya disease. Subsequent annual examinations have been stable, without signs of progression., Conclusions: This case demonstrates disparity between structural aberrations and final visual and neurological function and reinforces the association between MGS and intracranial vascular disruption. Full ancillary ophthalmic and neuroimaging studies should be performed in all patients with MGS with interval reassessments, even when the patient is asymptomatic and functionally intact.

Objective: To determine the efficacy and safety of azithromycin 1.5% eye drops in a paediatric population with purulent bacterial conjunctivitis., Patients and Methods: This was a multicentre, international, randomised, investigator-masked study in 286 children with purulent discharge and bulbar conjunctival injection. Patients received either azithromycin 1.5% eye drops (twice daily for 3 days) or tobramycin 0.3% eye drops (every 2 h for 2 days, then four times daily for 5 days). Clinical signs were evaluated on day (D) 0, 3 and 7, and cultures on D0 and D7. The primary variable was the clinical cure (absence of bulbar conjunctival injection and discharge) on D3 in the worse eye for patients with positive cultures on D0., Results: 286 patients (mean age 3.2 years; range 1 day-17 years) were included; 203 had positive cultures on D0. Azithromycin was superior to tobramycin in clinical cure rate on D3 (47.1% vs 28.7%, p=0.013) and was non-inferior to tobramycin on D7 (89.2% vs 78.2%, respectively). Azithromycin treatment eradicated causative pathogens, including resistant species, with a similar resolution rate to tobramycin (89.8% vs 87.2%, respectively). These results were confirmed in a subgroup of patients younger than 24 months old., Conclusions: Azithromycin 1.5% eye drops provided a more rapid clinical cure than tobramycin 0.3% eye drops in the treatment of purulent bacterial conjunctivitis in children, with a more convenient twice-a-day dosing regimen., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Six clinical studies of chronic electrical modulation of deep brain circuits published between 1968 and 2010 have reported effects in 55 vegetative or minimally conscious patients. The rationale stimulation was to activate the cortex through the reticular-thalamic complex, comprising the tegmental ascending reticular activating system and its thalamic targets. The most frequent intended target was the central intralaminar zone and adjacent nuclei. Hassler et al. also proposed to modulate the pallidum as part of the arousal and wakefulness system. Stimulation frequency varied from 8Hz to 250Hz. Most patients improved, although in a limited way. Schiff et al. found correlations between central thalamus stimulation and arousal and conscious behaviours. Other treatments that have offered some clinical benefit include drugs, repetitive magnetic transcranial stimulation, median nerve stimulation, stimulation of dorsal column of the upper cervical spinal cord, and stimulation of the fronto-parietal cortex. No one treatment has emerged as a gold standard for practice, which is why clinical trials are still on-going. Further clinical studies are needed to decipher the altered dynamics of neuronal network circuits in patients suffering from severe disorders of consciousness as a step towards novel therapeutic strategies., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.

Introduction: Uveal melanoma is the most common adult primary intraoculary tumor. Bilateral tumor is very rare, but must not be underestimated because early diagnosis and care improve the survival and the visual prognosis., Observation: We report the case of a patient treated for a left parapapillary choroidal melanoma by disk of ruthenium ((106)Ru), and a follow-up every 3 months for an atypical choroidal large-sized controlateral nævus levelling the macular area. This right nævus changed in 2009 leading to suspicion of a growing melanoma. Because the visual acuity of the left eye was limited to 20/2000, we wanted to confirm this growth before beginning a treatment. But for 3 years the tumor has remained stable and asymptomatic, with a disease staging still negative. To this day, no curative treatment has been started on the right eye., Discussion: In spite of clinical (To Find Small Ocular Melanomas (TFSOM) for example) and paraclinical arguments, it is sometimes difficult to differentiate a large nævus from an early melanoma. Evolution of the tumor often allows to confirm the diagnosis. However, the sole growth of a nævus is not specific of a choroidal melanoma. When confronted with suspicion of a small choroidal melanoma, some authors recommend an immediate treatment for the tumor; others prefer to confirm without a doubt a tumoral growth. It is necessary to weigh out the iatrogenic risks of a conservative treatment on the visual acuity in a monophtalm patient on one side, and the vital risk for the patient on the other side, which seems to be limited in case of small-sized melanoma with a slow evolution., Conclusion: A bilateral choroidal melanoma is rare. Systematic and repeated examinations of both eyes are essential. Management of these complicated cases often leads to discussion., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Purpose: To compare systemic absorption of three formulations of timolol eye drops: 0.1% timolol maleate gel, 0.5% timolol aqueous solution, and 0.5% timolol maleate gel., Methods: This was a double cross-over phase I study. Cross-over 1: two weeks of 0.1% timolol gel once daily, followed by a 3-week wash-out period and then two weeks of 0.5% timolol aqueous solution twice a day (group 1) or the reverse (group 2). Cross-over 2: two weeks of 0.1% timolol gel once daily, followed by a 3-week wash-out period, and then two weeks of 0.5% timolol gel once daily (group 3) or the reverse (group 4). Subjects underwent tonometry, blood sampling, and heart rate and blood pressure assessments (during bicycle exercise and head-up tilt tests) before and after instillation at the beginning and end of each treatment period., Results: Forty-three healthy volunteers were randomized: 11 subjects in groups 1, 2, and 3, and 10 subjects in group 4. Areas under the concentration-time curve (AUC) values after administration of timolol 0.5% formulations were 15- to 38-fold higher than those seen after administration of timolol 0.1% gel. Maximum timolol concentrations after instillation of 0.1% gel are reduced by almost 90% compared to concentrations obtained after both 0.5% aqueous solution and 0.5% gel instillation. The AUC between 0 and 12 h post-administration were also reduced by up to 93 to 98%., Conclusions: After treatment with a timolol 0.1% gel formulation, systemic concentrations found were considerably lower than after administration of timolol 0.5% gel or in aqueous solution., (Copyright © 2011. Published by Elsevier Masson SAS.)

Rhabdomyosarcoma is an extremely virulent rare tumor whose early diagnosis considerably improves survival and visual prognosis. We report the case of a 2-year-old child with levator palpebrae superioris muscle rhabdomyosarcoma revealed by a sudden and isolated blepharoptosis. Initially, clinical and imaging investigations did not show any abnormality but a painful tumor with some hematoma quickly developed, so the investigations were repeated. The CT-scan showed an extra-conal tumor that had developed at the superior part of the orbit. Histology confirmed the diagnosis of embryonic rhabdomyosarcoma. Because of its results, treatment consisting of chemotherapy associating ifosfamide, vincristine, actinomycin and orbital radiotherapy of 40 Gy with a local addition of 10 Gy were administrated with successful results after a 3-year-follow-up.

The optic nerve glioma is a relatively rare pathology in children and only a few cases have been described in infants. This paper reports the symptoms of this exceptional case in a 4-month-old child and reviews the differential diagnoses at this age. Finally, we discuss the diagnosis and therapeutic possibilities.

Purpose: To maintain its integrity, the human ocular surface (cornea and conjunctiva) has an absolute requirement for vitamin A and its active derivatives, the retinoic acids. These retinoids regulate transcriptional levels of target genes through the activation of members of a super-family of ligand-dependant nuclear receptors that feature retinoic acid receptors (RAR) alpha, beta, and gamma as well as retinoid X receptors (RXR) alpha, beta, and gamma. The expression patterns of these receptors have been partial characterized in rabbit, mouse, and human cornea and conjunctiva, but systematic tissue and cellular expression of the three RARs and three RXRs had to be completed at the adult human ocular surface. The first objective of our work was to define their expression patterns in term of genes and proteins for total human conjunctiva, cornea, and the major cell types comprising the adult human ocular surface. The second objective was to demonstrate the presence of different enzymes transforming vitamin A to retinoic acid and the functionality of this metabolic pathway in the corneal epithelium., Methods: Total mRNA was extracted from human total cornea, conjunctiva, corneal epithelial cells (primary culture and established cell line), corneal keratocytes (primary culture), corneal endothelial cells (established cell line), and conjunctival epithelial cells (established cell line) and was submitted to reverse transcription-polymerase chain reaction (RT-PCR) analysis to determine the expression patterns of the RARs and RXRs using specific primers. Immunological staining (via histochemistry and cellular chemistry) experiments were performed to better localize RAR and RXR proteins in the ocular surface at tissue and cellular levels. We also checked mRNA expression of cellular retinol binding proteins (CRBPs) and cellular retinoic acid binding proteins (CRABPs) with the enzymes involved in retinoic acid generation, i.e., alcohol dehydrogenases (ADHs) and retinal dehydrogenases (RALDHs) or degradation (Cyp26 family members). The enzymatic generation of functional retinoids was confirmed using epithelial corneal cells treated with specific inhibitors of retinol metabolism., Results: RAR alpha, RAR gamma, and RXR alpha are expressed in the cornea, conjunctiva, and all of their constitutive cells, whereas RXR gamma and RXR beta were never detected in the cornea or conjunctiva. RAR beta was absent in primary cultures of corneal keratinocytes. ADH3, ADH4, dehydrogenase/reductase (SDR family) 4 (DHRS4), dehydrogenase/reductase (SDR family) 9 (DHRS9), RALDH1, and RALDH3 are expressed in the ocular surface, as were the retinoid-binding proteins CRBP1, CRABP1, and CRABP2. Retinol dehydrogenase 4 (RODH4) was only detected in the conjunctiva. Corneal epithelial cells convert retinol into retinoic acid using an enzymatic pathway., Conclusions: For the first time, we have established an exhaustive description of the expressions patterns of RARs, RXRs, ADHs, RALDHs, CRBP, and CRABPs in the human ocular surface. Our results for the human ocular surface demonstrated the presence of all the metabolic and molecular actors of the retinoic acid signaling pathway. We also demonstrated the enzymatic conversion of retinol into active retinoids in the corneal environment.