Genotype-phenotype and OCT correlations in Autosomal Dominant Optic Atrophy related to OPA1 gene mutations: Report of 13 Italian families.

Mutations in OPA1 are responsible of 32-89% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA1 ADOA usually presents in childhood with bilateral, progressive visual loss due to retinal ganglion cells neurodegeneration, but environmental factors are supposed to influence onset and phenotype. Sixty Italian OPA1 mutations carriers (fifty-two symptomatic), belonging to thirteen families, underwent neuro-ophthalmologic evaluation. Visual acuity (n=60) and Optical Coherence Tomography (OCT) (n=12) were compared in missense mutations (OPA-M) versus haploinsufficiency-inducing mutations (OPA-H) and correlated with age. Presence of plus phenotypes was investigated. We found four known mutations, the most common being missense c.1034G>A, and a new missense mutation, c1193A>C, the latter in a 54-yrs old female with late-onset phenotype. Visual acuity, colour sensitivity, and optic disc atrophy were sensitive indicators of disease. OCT RNFL thickness was reduced in OPA1 compared to controls. OPA-M showed worst visual acuity than OPA-H, but not more frequent plus-phenotype, observed only in four OPA-H patients. In both groups, visual acuity worsened with age. Our data confirm worst vision in OPA-M, but not increased plus-phenotype. Since most patients belonged to nine families from south-eastern Sicily (a famous region for the cult of St. Lucy, patron of the blinds) local genetic and environmental factors might have accounted for the low occurrence of plus-phenotypes.

Intracranial idiopathic hypertension: 1-year follow-up study.

Standard guidelines for ongoing management, as well as definitive data about the long-term course of idiopathic intracranial hypertension (IIH) are not available. The aim of this study was to compare several clinical and instrumental variables as assessed at the time of diagnosis and then after 1 year in a sample of IIH patients. A total of 21 patients were studied. Our results confirmed that headache and TVO are the most frequent symptoms in IIH patients, and that overweight is a very common feature. A trend towards a favorable outcome in patients followed for 1 year and treated by usual medical therapy was found: intracranial pressure was lower at follow-up; improvement of headache and transient visual obscurations, as well as of papilledema, was reported in most patients. On the other hand, neuroradiological findings (such as empty sella, perioptic subarachnoid space distension, narrowing of the transverse sinuses) were substantially stable at follow. These findings may be relevant for future research as far as understanding the role of different clinical and instrumental findings as diagnostic items as well as predictors of outcome in IIH.

Headache prevalence and clinical features in patients with idiopathic intracranial hypertension (IIH).

Headache is a key symptom of idiopathic intracranial hypertension (IIH). Operational diagnostic criteria for "Headache attributed to IIH" are included in the international classification of headache disorders, the ICHD-2. The association of IIH with obesity was established by several reports. We investigate the prevalence of headache and its main clinical features in a clinical sample of IIH patients. The possible correlations between the presence of headache and body mass index (BMI) and intracranial pressure (ICP) levels were studied in a consecutive clinical series of patients, in whom diagnosis of IIH was confirmed by exclusion of secondary forms and by the evidence of increased ICP. Differences for age, BMI, and ICP between patients with and without headache and between males and females were assessed with Mann-Whitney U test. Spearman's correlation analysis was used to assess relationships between age, BMI, and ICP. P value < 0.05 was used to set statistical significance. 40 patients entered the study (9 males, 31 females; mean age 39, 8 years, SD 13.2). Headache was reported by 75 % patients. Those characteristics which are included in the present international diagnostic criteria for "Headache attributed to IIH" were reported by a remarkable proportion of the studied patients, but not by all. On the other hand, some headache features usually attributed to migraine forms, and which are not among the required criteria were present in some patients: pulsating quality and unilateral distribution of pain in around 20 %, and migrainous associated symptoms in more than 40 % of the sample. According to statistical analyses, no differences were found for age, BMI, and ICP between patients with and without headache. Our results confirmed the strong association between headache and IIH. Although no significant correlations between some of the key features of IIH were found in this study, we suggest that further studies on larger series--possibly with a longitudinal evaluation--are needed, to help clinicians in categorizing different subgroups among IIH patients as well as in identifying the main factors influencing the prognosis of this disorder.

Visual prognosis after indirect traumatic optic neuropathy.

OBJECTIVE: To investigate a possible correlation between final visual acuity and the presence at baseline of various systemic and local (orbital/ocular) signs in patients affected by indirect traumatic optic neuropathy. METHODS: 35 cases of traumatic optic neuropathy were examined retrospectively and 13 variables were tested. Univariate analysis with "no recovery of visual acuity" as the primary outcome was performed. Relative risk (RR) and 95% confidence intervals (CI) were calculated. Fisher's exact test was used for two variables to test differences between proportions. RESULTS: Four variables showed a significantly increased risk for no recovery of visual acuity: presence of blood within the posterior ethmoidal cells (RR = 2.25, 95% CI 1.25 to 4.04); age over 40 years (RR = 1.79, 1.07 to 2.99); loss of consciousness associated with traumatic optic neuropathy (RR = 2.21, 1.17 to 4.16); and absence of recovery after 48 hours of steroid treatment (p < 0.01, Fisher's exact test). Recovery documented at the first follow up visit after treatment was significantly associated with recovery at the last follow up visit (p < 0.01, Fisher's exact test). CONCLUSIONS: These four negative prognostic signs in patients affected by traumatic optic neuropathy may be useful in predicting the visual outcome in patients developing visual loss after head trauma and in deciding on the need for surgical treatment.

Optic neuritis: differential diagnosis.

Optic neuritis can be mimicked by other optic neuropathies and by anterior segment, choroidal or retinal diseases. Retinal diseases may cause central visual loss when they involve the macular or peripapillary area. Central serous retinopathy, hereditary retinal diseases, white dots syndromes and autoimmune retinopathies may present a clinical picture similar to that of optic neuritis. Complete neuro-ophthalmological examination must be performed to differentiate optic nerve damage from other ocular structures involvement. As in optic neuritis, optic disc and macula appearance may be completely normal in several retinal diseases. Fluorescein angiography and electrophysiological testing are relevant for the differential diagnosis in many challenging cases.

Non-demyelinating optic neuropathy: clinical entities.

Alternative causes of optic neuritis (ON), other than primary demyelination or non-demyelinating optic neuropathies which can mimic acute ON, should be rigorously considered if a patient with presumed ON does not follow the typical clinical course or has a normally appearing brain on magnetic resonance imaging. A thorough differential diagnosis includes viral and bacterial optic neuropathies, ischemic optic neuropathies, Devic's neuromyelitis optica, compressive or infiltrative optic neuropathies, Leber's hereditary optic neuropathy and toxic and deficiency optic neuropathies. All patients should undergo a complete neuroophthalmological examination to help exclude other diseases mimicking ON. Atypical clinical cases of optic neuropathy require further specific laboratory, neurophysiological and imaging tests to make a correct and early diagnosis.

Third, fourth, and sixth cranial nerve palsies.

Clinical manifestations of ocular motor palsies may differ according to the type and the localization of the lesions involving the third, fourth, and sixth cranial nerves. Topical diagnosis of the third, fourth, and sixth nerve palsies is therefore required before imaging studies and workup are performed. The development of modern imaging techniques has significantly improved the diagnosis of the disorders affecting the ocular motor nerves. This review covers the most important aspects, in terms of clinical signs and symptoms and differential diagnoses, of these cranial nerve palsies. The more recently published articles have added new disorders to the differential diagnosis of ocular motor palsy. Moreover, magnetic resonance imaging (MRI) has been confirmed to be the most important diagnostic tool in most cases. Finally, recently developed MRI techniques were presented and demonstrated to be more sensitive than conventional MRI in several cases.

Quantitative analysis of optic disc cupping in compressive optic neuropathy.

PURPOSE: Cupping of the optic disc, a characteristic sign of glaucoma, has been anecdotally described in association with compressive optic neuropathy. The aim of this study is to perform a masked, controlled, and quantitative measurement of the optic disc cup to determine if compressive lesions of the afferent visual pathway were associated with increased cupping. METHODS: The ratio of cup area:disc area of 29 patients with intracranial lesions impinging on the optic nerves and the chiasm (14 with pituitary adenomas, 7 with meningiomas, 6 with craniopharyngiomas, and 2 with aneurysms) was compared with those of 20 age-matched control subjects. The areal ratios were derived planimetrically from hand-drawn images of magnified stereophotographs. Patients were divided into three groups based on the degree of laterality of visual compromise. Uninvolved eyes served as an internal control for patients with unilateral disease. RESULTS: The median ratio of cup area:disc area was 0.37 for all eyes with visual compromise (n = 51) and 0.10 for control eyes, which was statistically significant (P = 0.0001). The median intereye difference in the ratio of cup area:disc area was 0.13 for patients with unilateral lesions and 0.04 for control subjects. This difference also was statistically significant (P = 0.0001). CONCLUSIONS: The finding of intereye asymmetry in patients with unilateral optic nerve compression is convincing evidence that the enlarged cup is an acquired feature. Several types of compressive lesions of the anterior visual pathway can be associated with increased cupping of the optic disc in the absence of increased intraocular pressure.

Tumors of the optic nerve and chiasm.

Optic nerve gliomas and meningiomas, which remain puzzling to clinicians, are reviewed with special attention to natural history, magnetic resonance findings, and appropriate management. New histopathological insights established the true neoplastic nature of optic nerve gliomas considered by most clinicians to be benign hamartomas. Unusual presenting manifestations and therapeutic alternatives of optic glioma have been also considered. Since the association of optic nerve gliomas and meningiomas with neurofibromatosis has long been recognized, special attention has been drawn to clinical, genetic, and ophthalmologic aspects of neurofibromatosis. New and unusual presenting manifestations, diagnostic and treatment opportunities concerning optic nerve involvement in metastatic disease, and lymphomatous proliferation are also described.