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44 EW FEATURE February 2011 Corneal diagnoses and systemic disease April 2012 Ophthalmologists can diagnose deadly disease at slit lamp by Jena Passut EyeWorld Staff Writer AT A GLANCE • Ophthalmologists often are the first to spot deadly Fabry's disease by seeing the most common ocular sign—cornea verticillata, also known as vortex keratopathy • Cornea verticillata usually doesn't affect sight, so patients often don't complain about it. They suffer from a whole host of other more pressing symptoms such as unexplained pain, nausea, extreme fatigue, hypertension, and renal issues • Fabry's disease patients present with a skin rash called angioker- atoma corporis diffusum, tiny dark red bumps, which often is present in the lower back, buttocks, and near the umbilicus • Enzyme replacement therapy is effective but expensive, practitioners say Fabry's disease presents with corneal verticillata I magine looking into the slit lamp and seeing something that, without a doubt, tells you the patient sitting there is suffering from a debilitating disease that will kill him. Now, imagine he has no idea. The patient has several seem- ingly unrelated symptoms, includ- ing a strange skin rash, nausea, unexplained pain, and hyperten- sion. When an ophthalmologist spots a characteristic cornea verticillata, the patient most likely is suffering from Fabry's disease, also known as Anderson-Fabry disease, angioker- atoma corporis diffusum, and alpha- galactosidase A deficiency. Fabry's disease patients lack an enzyme called alpha galactosidase A, without which the lipid ceramide trihexosi- dase builds up in the body and ulti- mately leads to renal failure and death. The chromosomal disease is X-linked recessive and affects mostly males. "The eye doctor is often the first to find this condition based on the cornea verticillata," said W. Barry Lee, M.D., Eye Consultants of At- lanta. "If the disease is diagnosed and the patient is referred for en- A patient with Fabry's disease and a characteristic cornea verticillata zyme replacement therapy, many of the symptoms of Fabry's that cause death can be delayed and prevented. These include renal failure and car- diomyopathy of the heart. The lipid, ceramide trihexosidase, builds up in the blood vessels, heart, and kidneys and ultimately leads to failure of these organs. With enzyme replace- ment, the lipid deposition is pre- vented. Without the enzyme, all patients ultimately die from renal failure and/or heart failure." Cornea verticillata, also known as vortex keratopathy, is the most common sign of Fabry's disease. Medications, including amiodarone, which helps patients with heart ar- rhythmias, can cause verticillata in the cornea, but Fabry's disease has a characteristic finding, Dr. Lee said. A practitioner may "also see dilated conjunctival vessels, a characteristic spoke-like cataract, and retinal vas- cular tortuosity," he said. Other medications that may cause cornea verticillata include chloroquine, hydroxychloroquine, indomethacin, and phenothiazines, Dr. Lee said. Most Fabry's disease patients won't complain about the corneal findings, according to Henry S. O'Halloran, M.D., pediatric oph- thalmologist, neuro-ophthalmolo- gist, and clinical instructor, Rady Children's Hospital, San Diego, and professor of ophthalmology, Univer- sity of Kentucky, Lexington. "Most people are asymptomatic and won't notice [ocular symptoms] or complain of decreased visual acu- ity unless it becomes really severe," Dr. O'Halloran said. Dr. O'Halloran said women may develop the disease, but it tends to be more benign in them. "If males get it, they have the worst course and worst outcome," he said. "If you diagnose it in a male, it's really bad news." Amiodarone deposition in the cornea Source (all): W. Barry Lee, M.D. Left untreated, patients likely will experience renal deficiency or failure. "That's very common," Dr. O'Halloran said. "People used to die from [renal failure] before kidney transplants became more common. This disease affects the cornea, but the bigger issue is it can cause all sorts of other diseases. [Patients] can pretty much get signs in any system of [their] body." Another common finding is a skin rash called angiokeratoma cor- poris diffusum, which often is pres- ent in the lower back, buttocks, and near the umbilicus. In fact, "a lot of times the diagnosis is made by dermatologists because people come in with skin conditions," Dr. O'Halloran said. Fabry's disease patients become increasingly frustrated as they expe- rience a multitude of aggravating symptoms including pain, fatigue, and gastrointestinal distress and often seek out several doctors before landing on a correct diagnosis. "As [patients] get older, it tends to get worse because it's a progres- sive disease," Dr. O'Halloran said. "There are some pretty severe mani- festations by the time a patient hits his 20s. A lot of times with these pa- tients, by the time they are diag- nosed, they have been to a bunch of different doctors, and they're frus- trated by the whole medical system. Their confidence is pretty much shattered. Early diagnosis makes it so much easier for them, and then there are treatment options." Diagnosis can be confirmed by chromosomal analysis, punch biopsy of skin lesions, or renal biopsy. "The easiest would be to do the skin punch biopsy," Dr. O'Halloran said. "It would show if there was an excessive buildup of lipids in the tis- sues." Treatment involves replacing the enzymes that the patient is miss- ing. "Two enzyme supplements are available, with the most widely known one being Fabrazyme [agalsidase beta, Genzyme, continued on page 50 Researchers use Nintendo WiiMotes to diagnose ocular torticollis A team of researchers in Seoul, South Korea, has developed a novel way for pediatric ophthalmologists to diagnosis children with ocular tor- ticollis. Called the infrared optical head tracker (IOHT), researchers used Nintendo WiiMote controllers to measure the angle of a person's head posture in real time. While it has several possible causes, torticollis can be caused by visual conditions such as visual field defects, nystagmus, or stra- bismus. "Torticollis occurs in about 1.3% of children," said author Jeong- Min Hwang, M.D., Seoul National University College of Medicine, in a press release. "Accurate measurement of the angle of the abnormal head position is crucial for evaluating disease progression and determining treat- ment or surgical plans in parties with ocular torticollis." Dr. Hwang and colleagues tested the IOHT on 20 normal adult subjects between 20 and 37 years of age and compared the results with the Cervical Range of Motion instrument (CROM, Performance Attainment Associates, St. Paul, Minn.). "The IOHT showed strong concordance with the CROM and relatively good test-retest reliability, thus proving its validity and relia- bility as a head-posture–measuring device," the researchers concluded. "Considering its high performance, ease of use, and low cost, the IOHT has the potential to be widely used as a head-posture–measuring device in clini- cal practice." Results of the study were published in the March issue of Investigative Ophthalmology & Visual Science (vol. 53 no. 3 1388-1396).