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New Test Diagnoses Blinding Disease
Devic's Syndrome Often Mistaken for MS.

Misdiagnosis of a severely paralyzing disease can now be averted due to a blood test developed by Mayo Clinic researchers and their Japanese collaborators. Often misdiagnosed as multiple sclerosis, neuromyelitis optica (NMO) also causes blindness in many sufferers.

The finding will help doctors correctly treat NMO -- also known as Devic's Syndrome -- sooner and more effectively. In some countries, misdiagnosis may be as high as 30%. Early diagnosis is important because NMO is best treated differently than multiple sclerosis.

NMO treatment requires immune suppressive medications, rather than the immune modulatory treatments typically prescribed for MS. NMO affects the optic nerves and spinal cord -- and within 5 years causes half of affected patients to lose vision in at least one eye. Many lose the ability to walk independently. The prognosis for loss of sight and permanent paralysis is much worse for patients who have NMO than for those who have MS. The cause of NMO is unknown. If diagnosed correctly before the myelin sheath is too damaged, plasma exchange therapy and immunosuppressive medications such as azathioprine and corticosteroids can be effective in stopping the damage and restoring nerve function.

"Early diagnosis and treatment are of paramount importance to reduce the severity of the course of NMO," says Vanda A. Lennon, M.D., Ph.D., Mayo Clinic neuroimmunologist who led the international research team. "With this biomarker, physicians are in a much better position to start optimal therapies sooner, and hopefully, lessen the impact of the disease."

It's not clear how many people have NMO, though it's generally regarded as rare in the United States. However, one Mayo Clinic physician in Rochester, Minn., has seen approximately 50 cases in the last 3 years, and an equal number of variants of NMO, such as recurrent transverse myelitis and recurrent optic neuritis. Ninety percent are women aged 30 to 60.

NMO is considerably more common in Japan and Asia. In Japan, roughly one-third of patients diagnosed with MS-like illness may actually have NMO.

MS isn't confined to optic nerve and spinal cord involvement. However, the symptoms of the two diseases overlap, and optic nerve and spinal cord involvement occur in both. NMO is particularly difficult to distinguish from MS in the early phases of the disease.

Without the new blood test, classic NMO can only be distinguished from MS by the extensive spinal cord lesions it inflicts spanning three or more segments of the bony spine, and by lack of MS-type lesions found by magnetic resonance imaging of the brain.

In developing the new test, blood samples were taken from patients in the United States and Japan and evaluated for the presence of a newly identified central nervous system autoantibody. However, the significance of this autoantibody wasn't initially appreciated. Based on a study of one group of patients with clinically recognized NMO, the researchers discovered that this "unclassified" autoantibody was common among these patients and therefore useful as a diagnostic biomarker for NMO.

Eye Injuries Take a Toll in Iraq
But High-Performance "Eye Armor" is Saving Sight.
By Jerry Helzner, Senior Editor

With insurgents relying on weapons such as mortars and roadside bombs whose explosions spray multiple fragments at high speed over a wide area, eye injuries to U.S. forces in Iraq have become an increasing concern. In fact, a senior military ophthalmologist says the percentage of U.S. troops sustaining combat-related eye damage in Iraq may be higher than in any other previous conflict.

Fortunately, the protective eyewear available to American soldiers and Marines has been greatly upgraded in recent years, with one particular product attracting a loyal following among the troops. But more on that later.

Military doctors and ophthalmologists serving in Combat Support Hospitals in Iraq are reporting that approximately 10% of all American troops they treat for battle-related wounds have some form of eye damage, almost always associated with other blast injuries. It's a figure that Col. Thomas Ward, M.D., consultant to the U.S. surgeon general in ophthalmology, told Ophthalmology Management that he accepts. He said that it's difficult to obtain an absolutely accurate count of eye injuries because they are placed in the more general category of "head and neck" wounds, but he believes the actual percentage may be higher than in any conflict dating back to the Civil War.

What Doctors are Treating

Maj. Michael Cohen, D.O., an Army doctor currently serving in a Combat Support Hospital near Mosul, Iraq, considers the 10% figure "fairly accurate" based on the casualties he's treated.

"Typically the injuries are related to rockets, mortars, or improvised explosive devices (IEDs)," says Maj. Cohen. "The injuries are related to shrapnel and dirt -- a lot of penetrating trauma. Probably the most common battle eye injury is a corneal foreign body/corneal abrasion. I have seen lots of casualties with metal or debris embedded in the cornea that is not easily removed. Quite frequently these are associated with a traumatic iritis, likely from the impact of the blast/injury. Anterior chamber hyphemas occur in about 10% of the traumatic eye injuries. Lots of lid lacerations as well. We also see about one or two orbital fractures per month."

Regarding nonhostile eye injuries, Maj. Cohen says corneal abrasions and traumatic iritis are at the top of the list.

"There is so much dust and dirt around here that small foreign bodies are common, which in turn cause mild abrasions," he notes. "Additionally, the allergen levels here are quite high and different from what we are accustomed to in the states, so we see a bit of allergic conjunctivitis. Chemical conjunctivitis is not uncommon as well, seen in soldiers handling fuels, solvents, or other chemicals. A few cases of blepharitis are likely related to the overall unclean environment and relatively poor hygiene."

Capt. Kerry E. Hunt, M.D., specialty leader in ophthalmology at the National Naval Medical Center in Bethesda, Md., leads a team that treats Marines and Navy personnel whose eye injuries are serious enough to require further attention in the United States.

He told Ophthalmology Management that battle-related injuries include blunt and penetrating trauma, with the biggest threat coming from explosions that send up multiple, small, high-speed fragments involving large areas of the body.

"I believe concussive forces are also playing a role in some of the eye injuries we have seen," says Capt. Hunt. "The head and neck and extremities aren't as easy to protect as the torso and so we are seeing a number of injuries to those parts of the body. There have been a large number of ocular injuries including penetrating foreign bodies (sometimes multiple), choroidal ruptures, vitreous hemorrhages, eyelid injuries and bony injuries involving the orbits. Our vitreoretinal and oculoplastic specialists have been the most busy. It is something we need to consider in the future to better meet the needs of modern conflict. Nonhostile eye problems center around environmental issues. Dirt, wind, allergens are more significant there than at home."

Developing "Eye Armor"

Given these assessments, it's clear that protective eyewear, or "eye armor" as the military calls it, can play a key role in reducing the number and severity of eye injuries in Iraq, and Afghanistan as well.

In looking back at the Persian Gulf War in 1991, David Nelson, deputy product manager for clothing and individual equipment at the Fort Belvoir, Va., Army installation, notes that Army personnel involved in that operation all received the "Sun, Wind and Dust" goggle, which was standard issue at that time.

"These were perfectly adequate in terms of providing anti-ballistic protection, but they had durability and comfort problems," says Nelson. "Also, the Army standard ballistic spectacles of the 90s lacked soldier acceptance because of their appearance. In simple terms, they didn't look cool."

About 4 years ago, the Army Rangers began working with Wiley X Eyewear of Livermore, Calif., to develop a versatile type of protective eyewear that wasn't bulky and that could be worn in multiple situations, including when jumping out of airplanes.

"We worked with the Rangers on the development of the product," says Dan Freeman, vice president of marketing for Wiley X. "They gave us good solid feedback and we made alterations to fit their needs."

The result was the SG-1, a multifunctional anti-ballistic eyewear "system" with anti-fog and anti-scratch shatterproof polycarbonate lenses. The SG-1 easily converts from a low-profile goggle to a stylish sunglass. Not only did the SG-1 exceed military standards for high-impact fragmentation protection, it also had a look that appealed to the soldiers.

The SG-1 has Cachet

Once the Rangers adopted the Wiley X SG-1, other elite military units such as the Navy SEALs, Army Special Forces and Marine bomb disposal teams also made it standard issue.

"There's no doubt the SG-1 acquired a cachet as the protective eyewear to have," says Freeman. "Many soldiers who weren't issued SG-1s purchased them with their own money." This is fairly common when soldiers want to upgrade their personal gear.

By the time U.S. troops entered Iraq in March 2003, the Wiley X had almost a cult following in the military based on its looks and performance. Though other companies such as Eye Safety Systems, Uvex, Oakley and Pyramex also produce protective eyewear that meets military standards and that's been purchased by the Army in relatively large numbers, it's the Wiley X that by all accounts has achieved the greatest soldier acceptance.

"We prized our Wileys," says a National Guard sergeant recently returned from Iraq. "We wanted them. We needed them."

By late 2003, as part of the Rapid Fielding Initiative (RFI) that upgraded all types of gear and equipment for soldiers deployed to Iraq and Afghanistan, the Army had ordered the Wiley X in the hundreds of thousands.

"It was important to issue protective eyewear that looks good and protects well," says David Nelson. "The goal was for the soldiers to wear it. But that doesn't mean the Army views the Wiley X as the product of choice. We have several excellent suppliers and the next big order for eyewear may well go to another company."

Eyewear Compliance Improves

Given the severity of the insurgents' attacks, some pointed directives from unit commanders, and the soldiers' fondness for their Wileys, eyewear compliance has gotten better. And that's especially important now that the military has provided so many of its members with laser vision correction. Refractive surgery allows soldiers to wear standard issue eye armor, which is a plus, but if these troops don't put on the eyewear, they don't even have spectacles to shield their eyes.

"We've made a big effort to get soldiers to wear their protective eyewear," notes Col. Ward. "Commanders are enforcing compliance, and we've recently seen a dropoff in eye injuries."

"At the beginning of the conflict, one of the challenges was establishing the culture of wearing eye armor," adds Capt. Hunt of the Navy. "That culture seems to be firmly established now."

But all other factors aside, the Wiley X and other recently upgraded eye armor are saving sight.

"I have seen pairs of Wileys destroyed and yet the soldier has sustained no eye injury at all,' says Maj. Cohen. "I cannot tell you how helpful that is to us. This eyewear is definitely a force multiplier."

Wall Street Eyes Wiley

With the legend of the Wiley X growing almost daily as soldiers recount stories of goggles saving them from serious injury, the company's sales to its traditional core markets -- motorcyclists, hunters and law enforcement -- have increased sharply. The company doesn't reveal sales figures, but it probably did more than $50 million in sales last year.

Freeman says the company could have sold even more pairs of the Wiley X but it has turned down large orders from countries such as Syria, which wanted to outfit its troops with the SG-1 goggles.

"We are very concerned about these products falling into the wrong hands," so we're careful about who we sell to," says Freeman.

Wall Street has noted the story behind the Wiley X and the positive brand recognition that the product has given the company in both military and commercial markets. Brokerage houses are clamoring to underwrite a stock offering that would allow Wiley shares to be publicly traded.

But the family-owned company is reluctant to go that route.

"We've got investment bankers trying to convince us to go public, but we want to retain control of the company. We have a lot of family members working here. We're satisfied being privately held," says Freeman.

Freeman says the interest from Wall Street is flattering but that what motivates Wiley management and employees is hearing from soldiers and Marines whose sight has been preserved by their eyewear.

"It's those letters and e-mail messages that let us know that we're doing our job," concludes Freeman.

Ophthalmology Management would like to hear from readers who have treated soldiers serving in Iraq. Please send e-mails to Jerry Helzner at helznergi@boucher1.com.

IN THE NEWS

B&L licenses Plasmin. Bayer HealthCare LLC, Biological Products Division, has granted Bausch & Lomb an exclusive worldwide license to Bayer's Plasmin technology for use in ophthalmic indications.

Plasmin is a product derived from processed human plasma. B&L believes Plasmin may have potential for use in developing novel therapies for ocular conditions. Bayer is pursuing development of Plasmin in nonocular indications where Plasmin could be used as a thrombolytic agent to dissolve blood clots in veins and arteries.

"We are interested in pursuing the development of Plasmin technology for potential use in treating multiple indications for which vitrectomy surgery now is used," said Gary M. Phillips, M.D., Bausch & Lomb corporate vice president, Global Pharmaceuticals and Vitreoretinal.

Inspire director resigns. Inspire Pharmaceuticals, Inc. said Gary D. Novack, Ph.D., has resigned from the company's board of directors to devote additional time to his growing consulting practice and his position as a Regent of the University of California. Inspire is currently seeking a replacement to fill Dr. Novack's vacated seat. OM

Clarification

The April 2004 (page 137) and October 2004 (page 122) issues of Ophthalmology Management cited results from an ongoing study (James P. McCulley, M.D., et al.) of fluoroquinolone penetration into the aqueous humor of cataract surgery patients. The results cited had been taken from abstracts, posters and podium presentations that were based on preliminary data.

The most current results at the time of this printing were presented during the American Academy of Ophthalmology/European Society of Ophthalmology joint meeting: the study involved 40 patients; the aqueous humor concentration in eyes dosed with moxifloxacin (Vigamox) was 1.88 +/- 0.52 µg/mL; the aqueous humor concentration in eyes treated with gatifloxacin (Zymar) was 1.06 +/- 0.36 µg/mL; p<0.007.

In the study, patients with otherwise healthy eyes duplicated post-op fluoroquinolone dosing by instilling the commercial formulation of Vigamox or Zymar q.i.d. 1 day before and 1 hour before scheduled routine cataract surgery.