M. Tariq Bhatti

Multiple sclerosis risk after optic neuritis: Final optic neuritis treatment trial follow-up

OBJECTIVE To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk. DESIGN Subjects in the Optic Neuritis Treatment Trial, who were enrolled between July 1, 1988, and June 30, 1991, were followed up prospectively for 15 years, with the final examination in 2006. SETTING Neurologic and ophthalmologic examinations at 13 clinical sites. PARTICIPANTS Three hundred eighty-nine subjects with acute optic neuritis. MAIN OUTCOME MEASURES Development of MS and neurologic disability assessment. RESULTS The cumulative probability of developing MS by 15 years after onset of optic neuritis was 50% (95% confidence interval, 44%-56%) and strongly related to presence of lesions on a baseline non-contrast-enhanced magnetic resonance imaging (MRI) of the brain. Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72% of patients with 1 or more lesions. After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions. Among patients without lesions on MRI, baseline factors associated with a substantially lower risk for MS included male sex, optic disc swelling, and certain atypical features of optic neuritis. CONCLUSIONS The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of MS. In the absence of MRI-detected lesions, male sex, optic disc swelling, and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS. This natural history information is important when considering prophylactic treatment for MS at the time of a first acute onset of optic neuritis.

Optical coherence tomography in the evaluation of neurofibromatosis type-1 subjects with optic pathway gliomas.

PURPOSE Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder, with an approximate incidence of 1 in 3,500. Optic pathway gliomas (OPGs) develop in 15% of individuals with NF1, commonly in childhood. OPGs are difficult to detect via a clinical inspection in children, often requiring magnetic resonance imaging (MRI). Given the significant visual risks associated with OPGs in NF1, there is a need for improved noninvasive techniques to diagnose OPGs in children; therefore, we studied optical coherence tomography (OCT) as a potential tool to assess optic nerve and retinal nerve fiber layer (RNFL) abnormalities. This prospective study was designed to evaluate OCT detection of RNFL loss from optic atrophy attributable to OPGs in a cohort of pediatric patients with NF1. METHODS With the use of Stratus OCT, directed testing with the Fast Macular Thickness and Fast RNFL Thickness protocol scans were performed on 9 subjects with NF1 and known OPGs, 6 subjects with NF1 without OPGs, and 15 controls. RESULTS NF1 subjects with OPGs had thinner RNFLs and macula when compared with age-matched controls and to NF1 subjects without OPGs. After applying the equivalence equation, the average RNFL thickness and macular volume in NF1 subjects without OPGs was equivalent to controls. CONCLUSIONS Our study suggests that OCT can be used to detect RNFL thinning secondary to OPGs in NF1 subjects. This objective tool shows promise as a useful adjunct to routine clinical ophthalmologic evaluation in children with NF1.

Clinical characteristics in 53 patients with cat scratch optic neuropathy.

OBJECTIVE To describe the clinical manifestations and to identify risk factors associated with visual outcome in a large cohort of patients with cat scratch optic neuropathy (CSON). DESIGN Multicenter, retrospective chart review. PARTICIPANTS Fifty-three patients (62 eyes) with serologically positive CSON from 5 academic neuro-ophthalmology services evaluated over an 11-year period. METHODS Institutional review board/ethics committee approval was obtained. Data from medical record charts were collected to detail the clinical manifestations and to analyze visual outcome metrics. Generalized estimating equations and logistic regression analysis were used in the statistical analysis. Six patients (9 eyes) were excluded from visual outcome statistical analysis because of a lack of follow-up. MAIN OUTCOME MEASURES Demographic information, symptoms at presentation, clinical characteristics, length of follow-up, treatment used, and visual acuity (at presentation and final follow-up). RESULTS Mean patient age was 27.8 years (range, 8-65 years). Mean follow-up time was 170.8 days (range, 1-1482 days). Simultaneous bilateral involvement occurred in 9 (17%) of 53 patients. Visual acuity on presentation ranged from 20/20 to counting fingers (mean, 20/160). Sixty-eight percent of eyes retained a visual acuity of 20/40 or better at final follow-up (defined as favorable visual outcome). Sixty-seven percent of patients endorsed a history of cat or kitten scratch. Neuroretinitis (macular star) developed in 28 eyes (45%). Only 5 patients had significant visual complications (branch retinal artery occlusion, macular hole, and corneal decompensation). Neither patient age nor any other factor except good initial visual acuity and absence of systemic symptoms was associated with a favorable visual outcome. There was no association between visual acuity at final follow-up and systemic antibiotic or steroid use. CONCLUSIONS Patients with CSON have a good overall visual prognosis. Good visual acuity at presentation was associated with a favorable visual outcome. The absence of a macular star does not exclude the possibility of CSON. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Severe dry eye syndrome after radiotherapy for head-and-neck tumors.

PURPOSE To investigate the incidence of severe dry eye syndrome (DES) after external beam radiotherapy for head-and-neck cancer and its dependence on the parameters relevant to external beam radiotherapy. METHODS AND MATERIALS The present retrospective study included 78 patients treated for primary extracranial head-and-neck tumors between 1965 and 2000, whose lacrimal apparatus/entire globe was exposed to fractionated external beam radiotherapy. The dose received by the major lacrimal gland was used for analysis. The end point of the present study was the ophthalmologic diagnosis of severe DES leading to vision compromise. RESULTS Of the 78 patients, 40 developed severe DES leading to visual compromise. The incidence of DES increased steadily from 6% at 35-39.99 Gy to 50% at 45-49.99 Gy and 90% at 60-64.99 Gy. With a mean of 0.9 years (range, 1 month to 3 years), the latency of DES was observed to be a function of the total dose and the dose per fraction. On univariate and multivariate analysis, the total dose (p < .0001 and p < .0001, respectively) and dose per fraction (p ≤ .0001 and p = .0044, respectively) were significant. However, age, gender, and the use of chemoradiotherapy were not. The actuarial analysis indicated a 5-year probability of freedom from DES of 93% for doses <45 Gy, 29% for 45-59.9 Gy, and 3% doses ≥60 Gy. A logistic normal tissue complication probability model fit to our data obtained a dose of 34 and 38 Gy corresponding to a 5% and 10% incidence of DES. CONCLUSION With a dose of 34 Gy corresponding to a 5% incidence of DES, the risk of severe DES increased, and the latency decreased with an increase in the total dose and dose per fraction to the lacrimal gland. The effect of chemoradiotherapy and hyperfractionation on the risk of DES needs additional investigation.

Delayed exacerbation of third nerve palsy due to aneurysmal regrowth after endovascular coil embolization.

A 72-year-old woman with a painful left third cranial nerve palsy due to a basilar artery aneurysm situated between the superior cerebellar and posterior cerebral arteries was treated with Guglielmi detachable coils (GDCs). Despite a good initial angiographic result with a small residual neck and improvement in the ocular motility and pain, the patient experienced worsening of the third cranial nerve palsy 15 months later. Cerebral angiography confirmed coil compaction with aneurysmal regrowth. A second endovascular coil embolization resulted in complete obliteration of the aneurysm. The patient experienced complete resolution of the pain and partial resolution of the third cranial nerve palsy. In some patients, a small residual aneurysm neck after endovascular embolization therapy with GDCs can result in delayed aneurysmal regrowth due to coil compaction. Clinical manifestations may herald this dangerous regrowth.

Characterization of retinal architecture in Parkinson's disease.

BACKGROUND Parkinsons disease (PD) is a neurodegenerative disorder associated with dopaminergic cell loss and α-synuclein aggregation in Lewy bodies, which has been demonstrated in the retina. METHODS We performed a spectral-domain optical coherence tomography (OCT) study in patients with PD and healthy controls to measure the peripapillary retinal nerve fiber layer thickness and macular volume. Intra-retinal segmentation was performed to measure the volume of the retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL), and outer nuclear (ONL) layers. Analysis was carried out blinded to the clinical status of study participants. RESULTS 101 PD and 46 healthy control eyes were included in the study. In PD patients, peripapillary retinal nerve fiber layer was not significantly thinner (96.95 μm vs 94.42 μm, p=0.08) but macular volume was (8.58 mm3 vs 8.33 mm3, p=0.0002). Intra-retinal segmentation showed that PD subjects have reduced GCL, IPL, INL and ONL volumes. In contrast, the OPL volume was significantly increased (0.81 mm3 vs 0.78 mm3 p=0.0214). CONCLUSIONS Thickening of the OPL is a novel finding which may correspond to the localization of α-synuclein in the OPL of PD patients. We hypothesize that the enlargement of the OPL may represent a potential biomarker of α-synuclein aggregation in PD. This may have significant clinical implications.

A Shot of Adrenaline

Acute macular neuroretinopathy is a rare disorder characterized by the sudden onset of unilateral or bilateral paracentral scotomas with relative sparing of the central vision that occurs mostly in young women. It is often characterized by wedge-like macular lesions. The cause of acute macular neuroretinopathy is unknown but viral, immunological, and vascular etiologies have been proposed. There is no current treatment and the visual prognosis is variable. We describe a young woman in whom this disorder was associated with the administration of epinephrine.

Thrombolytic therapy in central retinal artery occlusion: cutting edge therapy, standard of care therapy, or impractical therapy?

Purpose of review Numerous therapeutic options have been suggested for the treatment of central retinal artery occlusion (CRAO) such as ocular massage, anterior chamber paracentesis, physical exercise, and medication-induced reduction of intraocular pressure. Because of the lack of a proven effective treatment for CRAO, there has been a strong effort to develop alternative therapies. Recently, thrombolytic therapy has been suggested as a viable therapy for CRAO. The aim of this review is to provide an update on the progress of thrombolytic therapy for CRAO. Recent findings Although there is no consensus on a standardized treatment regimen for CRAO, emerging evidence suggests that thrombolytic therapy may be effective if administered promptly. Despite the benefit of thrombolytic therapy, on the basis of the results of case reports and case series, randomized controlled studies are necessary to ultimately prove the effectiveness of the treatment. Summary Thrombolytic therapy has yet to be validated as an effective treatment of CRAO. The execution of randomized, controlled trials is greatly needed to establish whether thrombolytic therapy can be considered standard of care therapy for CRAO.

Pediatric optic neuritis.

In clinical practice, the term optic neuritis (ON) refers to an idiopathic, demyelinating inflammatory condition of the optic nerve. As is the case with so many other pediatric diseases, when compared with a similar disease process in adults, pediatric ON is a distinct clinical entity from its adult counterpart in terms of epidemiology, clinical manifestations, and future neurological implications. In this review article, we will outline the clinical manifestations of pediatric ON, highlight the differences between pediatric ON and adult ON, discuss our current understanding of the relationship between pediatric ON and multiple sclerosis (MS), and emphasize the need for a prospective pediatric ON treatment trial.

Ocular myasthenia gravis

Purpose of review To review ocular myasthenia gravis (OMG), a localized form of myasthenia gravis clinically involving only the extraocular, levator palpebrae superioris, and orbicularis oculi muscles. Recent findings Ocular manifestations can masquerade as a variety of ocular motility disorders, including central nervous system disorders and peripheral cranial nerve palsies. While sparing the pupils, the diagnosis and management can be challenging. Summary Because several diagnostic and treatment options are available for OMG, clinicians must decide the sequence and combination based on the level of disease activity and patient disability.