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Not-to-Miss Findings for Neuro-Ophthalmology Problems and Conditions

A survey in January found that many neurologists may not be following the best evidence-based data when it comes to treating neuro-ophthalmologic problems such as optic neuritis (ON). This, among six papers that may have been missed by neurologists outside the subspecialty of neuro-ophthalmology, were identified as most noteworthy by two experts: Steven Galetta, MD, director of the Division of Neuro-Ophthalmology in the neurology department at the University of Pennsylvania in Philadelphia, and Eric Eggenberger, DO, professor and associate chair of neurology at Michigan State University in East Lansing. In phone interviews with Neurology Today, they described the main findings.


The survey of nearly 7,000 ophthalmologists and approximately 6,000 neurologists in the US, Canada, Australia, New Zealand, Denmark, France, Thailand, and Israel — reported in the Journal of Neurological Sciences - found that 14- to 65-percent of neurologists treat acute ON with oral prednisone 1 mg/kg per day, Dr. Galetta said, which was of no proven benefit in major clinical trials and doubled the risk of ON recurrence in the Optic Neuritis Treatment Trial (ONTT). For more rapid recovery of vision, IV steroids are recommended. In all countries, survey respondents often recommended steroids for the wrong reasons, Dr. Galetta said, such as trying to improve long-term visual outcome or to decrease the long-term risk of multiple sclerosis (MS).

“This study shows that despite our ability to get evidence-based data on how to treat ON, the message is not penetrating, particularly in some geographical areas,” Dr. Galetta said. “Neurologists believe the use of IV steroids may affect long-term visual outcomes, when in fact they may accelerate visual recovery by only several weeks. Also, ophthalmologists fail to recognize that IV steroids don't have a prolonged effect in delaying the onset of MS,” he noted.

Part of the problem is that the trial results may be published in journals that are not often read by specialists who treat ON, Dr. Galetta said.

A related study by the Optic Neuritis Study Group published in the June 2008 Archives of Neurology found that the strongest predictor of developing MS at 15 years was brain MRI abnormalities at the time of an ON attack. At 15 years of follow-up, 72 percent of patients with one or more lesion detected by brain MRI at the time of an ON attack developed MS compared with 25 percent of patients with no lesions.

In another important finding, Dr. Galetta explained that between years 10 and 15, patients with a normal MRI scan at baseline had only a 2 percent risk of converting to clinically definite MS, while those with MRI abnormalities had a 32 percent risk.


DR. STEVEN GALETTA: ”This study shows that despite our ability to get evidence-based data on how to treat ON [optic neuritis], the message is not penetrating, particularly in some geographical areas.”

“This suggests that a patient who has had ON and has a normal MRI may not need serial MRIs after 10 years, and maybe even after five years. The highest risk of developing MS after a normal MRI is in the first five years after ON,” Dr. Galetta said.

Perhaps the most exciting finding of this study, according to Dr. Galetta, is that at 15 years, no patients with a normal MRI and any of five following characteristics developed MS: a markedly swollen optic nerve; exudates in the macula; no pain at presentation of ON; no light perception vision; and hemorrhages in the optic nerve region.

“This information can provide reassurance to patients with ON, a normal MRI, and any of these five characteristics,” he said.


A cross-sectional study in the July 2008 Archives of Neurology suggests that two techniques for non-invasive retinal imaging — optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx) — provide complementary information about anterior visual pathway axonal loss in MS.

According to the study authors, both techniques should be used in clinical trials of ON and MS to examine neuroprotective and other disease-modifying therapies. Both techniques document retinal nerve fiber layer thinning in eyes of MS patients, and these measurements correlate well with visual function. GDx provides additional information by assessing microtubule integrity, which is an important aspect of axonal viability.

“This study shows that MS patients may have loss of retinal nerve fiber layers even in the absence of a history of ON,” Dr. Galetta said.

“Retinal nerve fiber layer thinning by OCT is a good structural marker for MS disease activity and has been shown to correlate with brain atrophy and cognitive changes. OCT is an easy-to-use and non-invasive technique for following patients with MS and for assessing axonal loss. Both tests [OCT and Gdx] are complementary. GDx provides an indirect measure of retinal nerve fiber layer thickness using the birefringence of microtubules. It can give us some idea of the viability of these axons,” Dr. Galetta explained.


A May 2008 paper in Investigative Ophthalmology & Visual Science reported that retinal nerve fiber layer thickness assessed by OCT was a reliable predictor of visual recovery (visual acuity or visual field defects) after surgery for parachiasmal tumors. The prospective study of 40 patients undergoing surgery for parachiasmal tumors demonstrated that those with measurable retinal nerve fiber layer loss before surgery were less likely to have visual recovery than those with normal retinal nerve fiber layer thickness.

A linear relationship was observed between increasing retinal nerve fiber layer thickness and increasing probability of near normal visual function, up to a thickness of approximately 85 microns.

“This study of retinal nerve fiber layer thickness could provide a reliable predictor of visual recovery after parachiasmal surgery,” Dr. Galetta said. “OCT may be a helpful in deciding whether surgery is necessary in patients with tumors in the region of the pituitary gland. Of note, 15 percent of these patients had normal visual fields but with a thin retinal nerve fiber layer. If replicated, these findings could have an impact on the management of parachiasmal lesions.”


DR. ERIC EGGENBERGER highlighted as noteworthy one study that suggests it may be beneficial to patch the hypertropic eye of patients with trochlear nerve palsy.

Patients with a thin retinal nerve fiber layer could be considered for more aggressive therapy, such as surgery or radiation, depending on tumor factors and patient characteristics, he added.


It can be challenging to differentiate skew deviation from trochlear nerve palsy (also called fourth nerve palsy), two conditions that can result from brain trauma or lesions in the posterior fossa and that manifest with ocular diplopia with a vertical component. A July 2008 paper in Archives of Ophthalmology suggests that changes in ocular torsion and vertical misalignment from the upright to the supine position can distinguish between these two conditions.

“Ocular torsion and vertical misalignment that decrease from the upright position to the supine position indicate skew deviation, whereas torsion and vertical misalignment that do not change significantly between the upright and supine position indicate trochlear nerve palsy,” wrote lead author Manoj V. Parulekar, FRCS, consultant ophthalmologist at the Birmingham Children's Hospital in the UK, formerly affiliated with the department of ophthalmology and visual sciences at The Hospital for Sick Children in Toronto, Canada.

Dr. Eggenberger explained that the classic three-step test is used to identify trochlear nerve palsy, but skew deviation may mimic this pattern in some patients, making a definitive diagnosis unlikely. The three-step test shows which eye is higher (hypertropic), determines whether the hypertropia is worse on left gaze or right gaze, and determines whether the hypertropia is worse on right head tilt or left head tilt.

“This paper adds an additional supine/upright test to the three-step test,” he noted.

The study included 10 patients with skew deviation, 14 with trochlear nerve palsy, and 12 healthy subjects. Ocular torsion was measured by the double Maddox rods test and vertical misalignment was measured by the prism and alternate cover test in both the upright and supine positions, respectively. Both the Maddox rods and the prism and alternative cover test are exam techniques that measure misalignment and deviation in a fixed position of gaze, Dr. Eggenberger explained.

When changing from the upright to the supine position, torsion was decreased by 83 percent in patients with skew deviation, but only by 2 percent in patients with trochlear nerve palsy and by 6 percent in healthy volunteers. Similarly, vertical misalignment was decreased by 74 percent in skew deviation, but only 5 percent in trochlear nerve palsy, and 6 percent normal controls.

A separate paper by lead author Jing Tian, PhD, a postdoctoral fellow in the Department of Neurology at Johns Hopkins University Medical School in Baltimore, and colleagues suggests that it may be beneficial to patch the hypertropic eye of patients with trochlear nerve palsy. The September 2008 paper in Investigative Ophthalmology & Visual Science described two monkeys with experimentally induced acute superior oblique palsy in one eye. The monkeys had their fourth nerve (trochlear nerve) severed and were then patched for six and nine days, respectively; then the patch was removed for the remainder of the 30-day study.

“During the patching, the amount of deviation in the paretic eye diminished. When the patch was off, the deviation grew larger, and the eye developed an increased hypertropia,” Dr. Eggenberger said. “This is intriguing, because it raises the question of whether we should patch patients with fourth nerve palsy, and if so, for how long,” he said.


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