Red-Tinted Contact Lenses May Improve Quality of Life in Retinal Diseases.

Supplemental digital content is available in the text. ABSTRACT: To determine the benefits provided by centrally red-tinted contact lenses on visual acuity, contrast sensitivity (CS), photophobia, and quality of life in patients with degenerative retinal diseases.We evaluated the impact of centrally red-tinted hydrogel contact lenses on nine patients (aged 15 to 22 years) with severe photophobia and poor visual acuity. Each patient underwent a full eye examination with and without contact lenses, including visual acuity at distance and near, CS, eye movement recording for nystagmus, refraction, and a fundus examination. All patients completed a low vision-adapted VFQ 25-Version 2000 quality-of-life questionnaire.Seven of nine patients demonstrated improvement in binocular visual acuity as well as improvement in CS with the tinted contact lenses. Subjectively, all patients described a major improvement in their photophobia both outdoors and indoors, as well as a marked improvement in quality of life.Red-tinted contact lenses may dramatically improve visual functions, outdoor performance, and quality of life of patients suffering from retinal diseases. These lenses should be a part of the regular assessment in specialty clinics treating patients with low vision, glare, and photophobia.

Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder.

Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by mutations or rearrangements in PLP1. It presents in infancy with nystagmus, jerky head movements, hypotonia and developmental delay evolving into spastic tetraplegia with optic atrophy and variable movement disorders. A clinically similar phenotype caused by recessive mutations in GJC2 is known as Pelizaeus-Merzbacher-like disease. Both genes encode proteins associated with myelin. We describe three siblings of a consanguineous family manifesting the typical infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy and peripheral neuropathy in adulthood. Magnetic resonance imaging and spectroscopy were consistent with a demyelinating leukodystrophy. Using genetic linkage and exome sequencing, we identified a homozygous missense c.399C>G; p.S133R mutation in MAG. This gene, previously associated with hereditary spastic paraplegia, encodes myelin-associated glycoprotein, which is involved in myelin maintenance and glia-axon interaction. This mutation is predicted to destabilize the protein and affect its tertiary structure. Examination of the sural nerve biopsy sample obtained in childhood in the oldest sibling revealed complete absence of myelin-associated glycoprotein accompanied by ill-formed onion-bulb structures and a relatively thin myelin sheath of the affected axons. Immunofluorescence, cell surface labelling, biochemical analysis and mass spectrometry-based proteomics studies in a variety of cell types demonstrated a devastating effect of the mutation on post-translational processing, steady state expression and subcellular localization of myelin-associated glycoprotein. In contrast to the wild-type protein, the p.S133R mutant was retained in the endoplasmic reticulum and was subjected to endoplasmic reticulum-associated protein degradation by the proteasome. Our findings identify involvement of myelin-associated glycoprotein in this family with a disorder affecting the central and peripheral nervous system, and suggest that loss of the protein function is responsible for the unique clinical phenotype.

Optic nerve vascular compression in a patient with a tuberculum sellae meningioma.

Background. Optic nerve vascular compression in patients with suprasellar tumor is a known entity but is rarely described in the literature. Case Description. We present a unique, well-documented case of optic nerve strangulation by the A1 segment of the anterior cerebral artery in a patient with a tuberculum sellae meningioma. The patient presented with pronounced progressive visual deterioration. Following surgery, there was immediate resolution of her visual deficit. Conclusion. Vascular strangulation of the optic nerve should be considered when facing progressive and/or severe visual field deterioration in patients with tumors proximal to the optic apparatus.

Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia.

OBJECTIVE: To present the clinical, molecular, and cell biological findings in a family with an autosomal recessive form of hereditary spastic paraplegia characterized by a combination of spastic paraplegia, optic atrophy, and peripheral neuropathy (SPOAN). METHODS: We used a combination of whole-genome linkage analysis and exome sequencing to map the disease locus and to identify the responsible gene. To analyze the physiologic consequences of the disease, we used biochemical and cell biological methods. RESULTS: Ten members of a highly consanguineous family manifested a childhood-onset SPOAN-like phenotype with slow progression into late adulthood. We mapped this disorder to a locus on chromosome 1q and identified a homozygous donor splice-site mutation in the IBA57 gene, previously implicated in 2 infants with lethal perinatal encephalomyopathy. This gene encodes the mitochondrial iron-sulfur (Fe/S) protein assembly factor IBA57. In addition to a severely decreased amount of normal IBA57 messenger RNA, a patient's cells expressed an aberrantly spliced messenger RNA with a premature stop codon. Lymphoblasts contained 10-fold-lower levels of wild-type, but no signs of truncated IBA57 protein. The decrease in functional IBA57 resulted in reduced levels and activities of several mitochondrial [4Fe-4S] proteins, including complexes I and II, while mitochondrial [2Fe-2S] proteins remained normal. CONCLUSIONS: Our findings reinforce the suggested specific function of IBA57 in mitochondrial [4Fe-4S] protein maturation and provide additional evidence for its role in human disease. The less decreased IBA57 protein level in this family explains phenotypic differences compared with the previously described lethal encephalomyopathy with no functional IBA57.

Parasellar meningiomas in pregnancy: surgical results and visual outcomes.

BACKGROUND: Rapid visual deterioration may occur as the result of the quick growth of parasellar meningiomas in the high-hormone/increased fluid retention milieu of pregnancy; however, surgery before delivery entails increased maternal-fetal risk. We present our experience in the management of parasellar meningiomas that compress the optic apparatus during pregnancy, with a focus on decisions regarding the timing of surgery. METHODS: Serial visual examinations and other clinical data for 11 women presenting from 2002 to 2012 with visual deterioration during pregnancy or delivery as the result of parasellar meningiomas involving the optic apparatus were reviewed. Indications for surgery during pregnancy included severely compromised vision, rapid visual deterioration, and early-to-midstage pregnancy with the potential for significant tumor growth and visual decrease before delivery. All patients underwent surgery with the use of skull base techniques via pterional craniotomy. An advanced extradural-intradural (i.e., Dolenc) approach, with modifications, was used in seven. RESULTS: All women achieved a Glasgow Outcome Score of 5 at discharge with no new neurologic deficits; all children are developing normally at a mean 4.5 years of age (range, 1-9.5 years). Surgery during pregnancy was recommended for six women: four operated at gestational weeks 20-23 had excellent postoperative visual recovery; two who delayed surgery until after delivery have permanent unilateral blindness. Among five others operated after delivery, four had good visual recovery and one has pronounced but correctable deficits. Three of five women diagnosed at gestational weeks 32-35 experienced spontaneous visual improvement after delivery, before surgery. CONCLUSIONS: We recommend that surgery be offered to patients during pregnancy when a delay may result in severe permanent visual impairment.

Safety of drilling for clinoidectomy and optic canal unroofing in anterior skull base surgery.

BACKGROUND: Skull base drilling is a necessary and important element of skull base surgery; however, drilling around vulnerable neurovascular structures has certain risks. We aimed to assess the frequency of complications related to drilling the anterior skull base in the area of the optic nerve (ON) and internal carotid artery (ICA), in a large series of patients. METHODS: We included anterior skull base surgeries performed from 2000 to 2012 that demanded unroofing of the optic canal, with extra- or intradural clinoidectomy and/or drilling of the clinoidal process and lateral aspect of the tuberculum sella. Data was retrieved from a prospective database and supplementary retrospective file review. Our IRB waived the requirement for informed consent. The nature and location of pathology, clinical presentation, surgical techniques, surgical morbidity and mortality, pre- and postoperative vision, and neurological outcomes were reviewed. RESULTS: There were 205 surgeries, including 22 procedures with bilateral optic canal unroofing (227 optic canals unroofed). There was no mortality, drilling-related vascular damage, or brain trauma. Complications possibly related to drilling included CSF leak (6 patients, 2.9 %), new ipsilateral blindness (3 patients, 1.5 %), visual deterioration (3 patients, 1.5 %), and transient oculomotor palsy (5 patients, 2.4 %). In all patients with new neuropathies, the optic and oculomotor nerves were manipulated during tumor removal; thus, new deficits could have resulted from drilling, or tumor dissection, or both. CONCLUSION: Drilling of the clinoid process and tuberculum sella, and optic canal unroofing are important surgical techniques, which may be performed relatively safely by a skilled neurosurgeon.

[Bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse in T-cell acute lymphoblastic leukemia].

T-cell acute lymphoblastic leukemia is a hematologic malignancy with propensity to involve extramedullary organs including the eyes. Optic nerve infiltration is relatively rare. This is the case study of a 25-year-old- man who was in full remission following treatment for T-cell acute lymphoblastic leukemia and presented with bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse. The patient was treated with urgent radiotherapy and systemic dexamethasone. Over the following period, gradual resolution of optic disc swelling was noted in both eyes with marked improvement in vision in the right eye. Unfortunately, a few weeks later, a full blown hematological relapse was diagnosed. Salvage chemotherapy was instituted but was complicated by tumor lysis syndrome and septicemia that proved to be fatal. Ophthalmic assessment is essential in patients with hematological malignancies in order to diagnose ocular involvement as a result of malignant infiltration, hematological disturbances or as a complication of systemic therapy.

Giant anterior clinoidal meningiomas: surgical technique and outcomes.

OBJECT: Surgery for giant anterior clinoidal meningiomas that invade vital neurovascular structures surrounding the anterior clinoid process is challenging. The authors present their skull base technique for the treatment of giant anterior clinoidal meningiomas, defined here as globular tumors with a maximum diameter of 5 cm or larger, centered around the anterior clinoid process, which is usually hyperostotic. METHODS: Between 2000 and 2010, the authors performed 23 surgeries in 22 patients with giant anterior clinoidal meningiomas. They used a skull base approach with extradural unroofing of the optic canal, extradural clinoidectomy (Dolenc technique), transdural debulking of the tumor, early optic nerve decompression, and early identification and control of key neurovascular structures. RESULTS: The mean age at surgery was 53.8 years. The mean tumor diameter was 59.2 mm (range 50-85 mm) with cavernous sinus involvement in 59.1% (13 of 22 patients). The tumor involved the prechiasmatic segment of the optic nerve in all patients, invaded the optic canal in 77.3% (17 of 22 patients), and caused visual impairment in 86.4% (19 of 22 patients). Total resection (Simpson Grade I or II) was achieved in 30.4% of surgeries (7 of 23); subtotal and partial resections were each achieved in 34.8% of surgeries (8 of 23). The main factor precluding total removal was cavernous sinus involvement. There were no deaths. The mean Glasgow Outcome Scale score was 4.8 (median 5) at a mean of 56 months of follow-up. Vision improved in 66.7% (12 of 18 patients) with consecutive neuroophthalmological examinations, was stable in 22.2% (4 of 18), and deteriorated in 11.1% (2 of 18). New deficits in cranial nerve III or IV remained after 8.7% of surgeries (2 of 23). CONCLUSIONS: This modified surgical protocol has provided both a good extent of resection and a good neurological and visual outcome in patients with giant anterior clinoidal meningiomas.

Demyelination affects temporal aspects of perception: an optic neuritis study.

OBJECTIVE: Visual Evoked Potentials (VEPs) following optic neuritis (ON) remain chronically prolonged, although standard visual tests indicate full recovery. We hypothesized that dynamic visual processes, such as motion perception, may be more vulnerable to slowed conduction in the optic nerve, and consequently be better associated with projection rates. METHODS: Twenty-one patients with acute unilateral, first-ever ON were studied during 1 year. Static visual functions (visual acuity, color perception, visual field, and contrast sensitivity), dynamic visual functions (motion perception), and VEPs were assessed repeatedly. RESULTS: Visual and electrophysiological measurements reached maximal performance 4 months following the acute phase, with no subsequent improvement. Whereas VEP amplitude and static visual functions recovered, VEP latency remained significantly prolonged, and motion perception remained impaired throughout the 12-month period. A strong correlation was found between VEP latencies and motion perception. Visual performance at 1 month was strongly predictive of visual outcome. For static functions, patients who showed partial recovery at 1 month subsequently achieved full recovery. For dynamic functions, the rate of improvement was constant across patients, independent of the initial deficit level. INTERPRETATION: Conduction velocity in the visual pathways correlated closely with dynamic visual functions, implicating the need for rapid transmission of visual input to perceive motion. Motion perception level may serve as a tool to assess the magnitude of myelination in the visual pathways. The constancy across patients may serve as a baseline to assess the efficacy of currently developing neuroprotective and regenerative therapeutic strategies, targeting myelination in the central nervous system.

Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis.

AIM: To describe the histological changes in the optic nerve (ON) after experimental segregation of cerebrospinal fluid (CSF). METHODS: In seven sheep, a silicone band was placed around one ON to compress the subarachnoid space (SAS) surrounding the nerve, thus blocking the flow of CSF without compressing the ON itself. After 4 or 21 days, both the ligated and untouched ONs were removed and evaluated histologically. RESULTS: All treated ONs showed marked loss of axons, destruction of myelin and swelling of meningoepithelial cells, most pronounced in the proximal ON adjacent to the globe at the location most distant to the ligature. There was no significant difference in histological findings between the ONs that were ligated for 4 days and those with 21 days of ligature. CONCLUSION: CSF segregation in the ON by blocking the SAS leads within 4 days to severe nerve damage. The increasing severity of these changes with increasing distance from the site of the ligature argues against simple pressure- or microperfusion-dependent effects and supports the hypothesis that interruption of CSF flow in the SAS of the ON can produce damage due to a change of CSF flow and content.

Normal and abnormal fMRI activation patterns in the visual cortex after recovery from optic neuritis.

Recovery to normal or near normal visual acuity after an optic neuritis episode is common, despite frequent persistence of conduction abnormalities, evident in prolonged visual evoked potential (VEP) latencies. Improvement of visual function is commonly attributed to peripheral nerve recovery. However, central reorganization processes may also be involved. To assess this, we compared the patterns of fMRI activation, elicited by stimulation of the affected and the normal eye, along the visual cortical hierarchy. Activation was assessed in 8 subjects, which recovered clinically from an episode of optic neuritis but still had prolonged VEP latencies. In all patients, reduced fMRI activation was seen in V1 during stimulation of the affected eye, compared to the normal eye. The fMRI signal difference decreased in magnitude with progression along the visual hierarchy, and in some regions within the lateral occipital complex even showed the opposite preference (for the affected eye). These results may indicate a built-in robustness of the object-related areas to disruption of the visual input. Alternatively, it could reflect an adaptive functional reorganization of the cortical response to an abnormal input.

Necrobiotic xanthogranuloma associated with choroidal infiltration and syncytial giant cell hepatitis.

A 31-year-old woman developed necrobiotic xanthogranuloma (NXG), a thickened choroid, and syncytial giant cell hepatitis, a previously unreported association. NXG and syncytial giant cell hepatitis may have a common autoimmune pathogenesis.

A novel autosomal recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12.

We describe a new autosomal recessive myopathy of early onset and very slow progression distinguished by the prominent external ophthalmoplegia in 16 subjects of eight families from a large and highly inbred Arab community. Characteristic clinical features include mild facial and skeletal muscle weakness and atrophy more pronounced proximally in the upper limbs, facial dysmorphism and scoliosis associated with conjugate, non-restrictive ocular motility impairment greatest in the upgaze and without ptosis or aberrant eye movements. Orbital MRI in the patients demonstrated atrophy with fatty replacement of the oculorotatory muscles. The major pathological alteration on skeletal muscle biopsy was a marked type 1 fibre predominance with core-like formations. A genome wide search for regions of homozygosity in the affected members from two informative families identified linkage with chromosome 17p13.1-p12 markers. Maximum two-point logarithm of odds scores were obtained at loci D17S1803 and AFMA070WD1 (Zmax = 3.74 at = 0). Two independent recombination events at D17S1812 and D17S947 further defined a critical region of 12 cM. Several genes map to this interval, including a cluster of sarcomeric myosin heavy chain genes. One of these genes, MYH2, is involved in inclusion body myopathy 3, but no exonic mutations were found by direct sequencing. The molecular basis for this new myopathy remains to be identified.