Category Archives: Eye Diseases

Macular Degeneration Prevention

Avoiding the risk factors for macular degeneration may help prevent it. This includes avoiding tobacco smoke and eating a diet low in saturated fat and rich in antioxidants. Some doctors suggest that wearing UV-blocking sunglasses reduces risk. Use of estrogen in postmenopausal women is associated with a lower risk of developing ARMD.

Key Terms

DrusenTiny yellow dots on the retina that can be soft or hard and that usually do not interfere with vision.

FoveaA tiny pit in the macula that is responsible for sharp vision.

NeovascularizationGrowth of new capillaries.

PhotoreceptorsSpecialized nerve cells (rods and cones) in the retina that are responsible for vision.

RetinaThe light-sensitive membrane at the back of the eye that images are focused on. The retina sends the images to the brain via the optic nerve.

Macular Degeneration Treatment

While vision loss cannot be reversed, early detection is important because treatments are available that may halt or slow the progression of the wet form of ARMD. Some treatments for the dry form were still in early clinical trials in 2001.

In wet-type ARMD and in senile disciform macular degeneration, new capillaries grow in the macular region and leak. This leaking of blood and fluid causes a portion of the retina to detach. Blood vessel growth, called neovascularization, can be treated with laser photocoagulation in some cases, depending upon the location and extent of the growth. Argon or krypton lasers can destroy the new tissue and flatten the retina. This treatment is effective in about half the cases but results may be temporary. A concern exists that laser therapy causes the laser to destroy the photoreceptors in the treated area. If the blood vessels have grown into the fovea (a region of the macula responsible for fine vision), treatment may be impossible. Because capillaries can grow quickly, this form of macular degeneration should be handled as an emergency and treated immediately.

Photodynamic therapy (PDT) is a promising new treatment approved by the Food and Drug Administration in 2000. With PDT, the patient is given a light-activated drug intravenously with no damage to the retina. The drug, Visudyne, is absorbed by the damaged blood vessels. The affected area on the retina is exposed to a nonthermal laser light that activates the drug exactly 15 minutes after the infusion begins. It must be exactly 15 minutes for the treatment to be successful. The light chemically alters the drug, and any leakage from choroidal neovascularization (CNV) ceases. Patients require retreatment every three months during the first year of therapy, and should be advised to avoid bright light or sun exposure for several days after therapy.

Another form of treatment for the wet form of ARMD is radiation therapy with either x rays, or a proton beam. Growing blood vessels are sensitive to treatment with low doses of ionizing radiation. The growth of nerve cells in the retina is stunted. They are insensitive and thus are not harmed by this treatment. External beam radiation treatment has shown promising results at slowing progression in limited, early trials.

Other therapies that are under study include treatment with alpha-interferon, thalidomide, and other drugs that slow the growth of blood vessels. Subretinal surgery also has shown promise in rapid-onset cases of wet ARMD. This surgery carries the risk of retinal detachment, hemorrhage, and acceleration of cataract formation. A controversial treatment called rheotherapy involves pumping the patient’s blood through a device that removes some proteins and fats. As of 2001, this had not been proven to be safe or effective.

Consumption of a diet rich in antioxidants (beta carotene and the mixed carotenoids that are precursors of vitamin A, vitamins C and E, selenium, and zinc), or antioxidant nutritional supplements, may help prevent macular degeneration, particularly if started early in life. Research has shown that nutritional therapy can prevent ARMD or slow its progression once established.

Researchers also are working on therapies to treat the dry form of macular degeneration. Low-energy laser treatment for drusen is currently in clinical trials as of 2001. In this treatment the ophthalmologist uses a diode laser to reduce the drusen level. Some ophthalmologists were already performing this procedure “off-label,” without FDA approval.

Another treatment, approved overseas but not in the United States, treats dry ARMD by implanting a miniaturized telescope to magnify objects in the central field of vision. This does not treat the disease, but aids the patient’s vision in only the very severe cases of ARMD.

The dry form of ARMD is self-limiting and eventually stabilizes, with permanent vision loss. The vision of patients with the wet form of ARMD often stabilizes or improves even without treatment, at least temporarily. However, after a few years, patients with this type are usually left without acute central vision.

Many macular degeneration patients lose their central vision permanently and may become legally blind. However, macular degeneration rarely causes total vision loss. Peripheral vision is retained. Patients can compensate for central vision loss, even when macular degeneration renders them legally blind. Improved lighting and low-vision aids can help even if visual acuity is poor. Vision aids include special magnifiersallowing patients to read, and provide telescopic aids for long-distance vision. The use of these visual aids plus the retained peripheral vision assist in maintaining patient independence.

Macular Degeneration Diagnosis

Optometrists and ophthalmologists, with assistance from ophthalmic assistants, technicians and nurses, should carefully screen patients who are at risk for macular degeneration. These include patients older than 60; patients with hypertension or cardiovascular disease; cigarette smokers; patients with a first-degree family (sibling or maternal) history of vision loss from ARMD regardless of age; patients with aphakia or pseudophakia; or someone with a cataract, and patients with a history that indicates significant cumulative light exposure.

The ophthalmic assistant will take a careful history and log these risk factors. The patient then should have a complete ocular examination. Vision tests, performed by the physician or a skilled ophthalmic assistant, examine best corrected visual acuity, as well as near monocular visual acuity; refraction; biomicroscopy; tonometry; and stereoscopic fundus examination with pupillary dilation. Though rarely used even if ARMD is suspected, a central 10-degree computerized automated perimetry might be utilized along with fundus photography and laser ophthalmoscope scanning.

After preliminary testing, specific tests are performed to determine macular degeneration. To make the diagnosis, the doctor dilates the pupil with eye drops and examines the interior of the eye, examining the retina for the presence of drusen, small white-yellow spots in the macular area, and for gross changes in the macula such as thinning. The doctor also administers a visual field test to search for blank spots in the central vision. The doctor might order fluorescein angiography (intravenous injection of fluorescent dye followed by visual examination and photography of the back of the eye) to determine if blood vessels in the retina are leaking. Retinal pigmented epithelium (RPE) mottling that occurs, like the drusen, due to ateriorsclerotic changes of the macula decreasing the blood supply, can also be indicated through a thorough examination.

A central visual field test called an Amsler grid is usually given to patients who are suspected of having ARMD. It is a grid printed on a sheet of paper (also presented for home use every week). When viewing a central dot on the page, the patient should note if any of the lines appear to be wavy or missing. This could be an indication of fluid and the onset of wet ARMD. High-risk patients particularly will be urged to schedule more frequent checkups.

Although ophthalmologists and optometrists can accurately diagnose macular degeneration, attending physicians may want to consult with a retinal specialist for the best treatment protocols.

Macular Degeneration Causes and Symptoms

Age-related macular degeneration is intrinsic to aging for some individuals, but not all. People with an ARMD-affected family member have an increased the risk for its development. A slightly higher incidence occurs in females, although males and females are considered to be equally at risk. Whites and Asians are more susceptible to developing ARMD than blacks, in whom the disorder is rare.

The cause of ARMD is thought to be arteriosclerosis in the blood vessels supplying the retina. Certain risks for the heart are considered similar risks to those that contribute to the development of macular degeneration. Smoking increases the risk of developing wet-type ARMD, and may increase the risk of developing dry-type as well. Dietary fat also increases the risk. In one study of older (age 45-84) Americans, signs of early ARMD were 80% more common in the group who ate the most saturated fat compared to those who ate the least. Low consumption of antioxidants, such as foods rich in vitamin A, is associated with a higher risk. It is generally believed that exposure to ultraviolet (UV) light may contribute to disease development, but this has not been proven conclusively.

A study reported in Ophthalmology in 2000 concluded that hypertension, thyroid hormones, and antacids are associated with certain types of ARMD. The issue of antacids is not widely recognized since no determination has yet been made regarding whether the antacids themselves lead to the disease, or whether it is the stomach problems that are a contributing factor. Obesity was also found to be a factor in this study.

The main symptom of macular degeneration is a central vision change. The patient may experience blurred central vision or a blank spot on the page when reading, visual distortion such as bending of straight lines, and images might appear smaller than is the actual object. Some patients notice a change in color perception, or abnormal light sensations. These symptoms can emerge suddenly and become progressively worse. Patients should be advised that a sudden onset of symptoms, particularly vision distortion, is an indication for immediate evaluation.

Macular Degeneration

Macular degeneration is the progressive deterioration of a critical region of the retina called the macula. The macula is 3-5 mm and is responsible for central vision. This disorder leads to irreversible loss of central vision, although peripheral vision is retained. In the early stages, vision may be gray, hazy, or distorted.

Macular degeneration is the most common cause of legal blindness in people over 60, and accounts for approximately 11.7% of blindness in the United States. About 28% of the population over age 74 is affected by this disease.

Age-related macular degeneration (ARMD) is the most common form of macular degeneration. It is also known as age-related maculopathy (ARM), aged macular degeneration, and senile macular degeneration. Approximately 10 million Americans have some vision loss due to ARMD.

ARMD is subdivided into a dry (atrophic) and a wet (exudative) form. The dry form is more common and accounts for 70-90% of cases of ARMD. It progresses more slowly than the wet form and vision loss is less severe. In the dry form, the macula thins over time as part of the aging process and the pigmented retinal epithelium (a dark-colored cell layer at the back of the eye) is gradually lost. Words may appear blurred or hazy, and colors may appear dim or gray.

With wet ARMD, new blood vessels grow underneath the retina and distort the retina. These blood vessels can leak, causing scar tissue to form on the retina. The wet form may cause visual distortion and make straight lines appear wavy. A central blind spot develops. The wet type progresses more rapidly and vision loss is more pronounced.

Less common forms of macular degeneration include:

Cystoid macular degeneration: Vision loss in the macula due to fluid-filled areas (cysts) in the macular region. This may be a result of other disorders, such as aging, inflammation, or high myopia.

Diabetic macular degeneration: Deterioration of the macula due to diabetes.

Senile disciform degeneration (Kuhnt-Junius macular degeneration): A severe type of wet ARMD that involves hemorrhaging in the macular region. It usually occurs in people over 40 years old.

Graves’ disease – Screen for Fetal Hyperthyroidism

Women with a history of Graves’ disease should be screened for fetal hyperthyroidism at 2426 weeks’ gestation, Dr. Ingrid Block advised at a meeting on antepartum and intrapartum management.

These women should have their thyroid-stimulating immunoglobulin (TSI) levels measured at the beginning of pregnancy and again at 24-26 weeks. The results may help confirm a suspicion of fetal hyperthyroidism or prompt further analysis, she said at the meeting, sponsored by the University of California, San Francisco.

In most laboratories, a normal background TSI titer will be less than 130%. A TSI of 350% with a fetal heart rate below 160 beats per minute suggests a low risk for fetal hyperthyroidism, but continued monitoring in these cases is prudent, said Dr. Block of the university.

A fetal heart rate above 160 beats per minute typically characterizes the disease.

A TSI of 350%-500% puts the fetus at moderate risk for hyperthyroidism, and a TSI of more than 500% puts the fetus at high risk.

Fetal hyperthyroidism complicates 1% of pregnancies in U.S. women with a history of Graves’ disease. With active maternal disease, most fetuses will be protected by their mothers’ antithyroid medication.

Physicians should be especially careful to look for fetal hyperthyroidism in women with a history of Graves’ disease who are on thyroid hormone replacement therapy but have discontinued antithyroid medication. These women may still have thyroid-stimulating hormone (TSH)-receptor antibodies, which puts them at highest risk for fetal hyperthyroidism, she said.

In general, a maternal TSH-receptor antibody titer above 350% increases the likelihood that the fetus has hyperthyroidism.

Diagnosis is based on clinical symptoms and ultrasound findings. Ultrasound studies should be ordered for women with a history of Graves” disease to look for fetal, goiter or a hyperextended fetal neck that could indicate goiter.

Growth retardation, increased fetal motility, or accelerated fetal bone maturation also can be signs of fetal hyperthyroidism. If the woman had a previous pregnancy complicated by fetal hyperthyroidism, this also increases the risk for the disease in the current pregnancy.

In rare cases, obtaining a sample of fetal cord blood may be necessary to make the diagnosis, but this procedure carries a 1% risk of fetal loss.

Physicians should therefore weigh the risks and benefits carefully and consult a pediatric endocrinologist before performing this procedure.

Smoking may Boost Dermopathy Risk in Graves’ Disease

Patients with two of the most serious, manifestations of Graves disease–acropachy and dermopathy–are three times more likely to have a history of tobacco use and are five times more likely to be current smokers than patients with another thyroid disease, Hashimoto’s thyroiditis.

A small study presented at the annual meeting of the American Association of Clinical Endocrinologists found that 31 of 39 patients with acropachy (79%), 81 of 102 patients with dermopathy (79%), and 13 of 46 patients with Hasbimoto’s thyroiditis (28%) had a history smoking.

More than half of patients with dermopathy or acropachy reported that they were current smokers, compared with 9% of patients with Hashimoto’s thyroiditis.

“Several reports have indicated that tobacco use is a risk factor for Graves’ ophthalmopathy,” noted Dr. Vahab Fatourechi of the Mayo Clinic, Rochester, Minn., in a poster presented at the meeting.

But the frequency of tobacco use in patients with even more severe manifestations of Graves’ disease had never been studied. These manifestations include acropachy, an inflammatory disorder of connective tissue that involves clubbing of the fingers and toes and can lead to elephantiasis, and dermopathy, also known as pretibial or localized myxedema, which is an infiltrative condition of the dorsum of the legs and feet characterized by hyperpigmented patches and plaques.

Dr. Fatourechi and coinvestigator Mitra M. Fatourechi, a medical student at the University of Minnesota, Minneapolis, compared age- and sex-matched patients with acropachy, dermopathy, or Hashimoto’s thyroiditis, finding a striking association between the more severe conditions and current or past tobacco use.

“Although the pathogenesis of this association is unclear and suggested modification of the immune process by smoking needs further confirmation, a strong case can be made for considering tobacco use as a risk factor for severity of autoimmune manifestations of Graves’ disease,” Dr. Fatourechi said. “Patients with Graves’ disease should be strongly advised against smoking.”

Graves’ eye Disease Uncommon after Radioiodine

Graves’ ophthalmopathy is uncommon in the first year after ablative radioiodine therapy, Julie E. Hallanger-Johnson, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Graves’ ophthalmopathy affects up to 30% of patients with Graves’ disease, with severe effects reported in 3%-5%.

The influence of radioiodine therapy on the development of Graves’ ophthalmopathy is not clear and is considered a controversial area.

Randomized data of good quality are not available, and no reliable clinical or laboratory predictors of the development of Graves’ ophthalmopathy following radioiodine therapy have been identified, although tobacco use has been suggested as a possible risk factor, said Dr. Hallanger-Johnson of the Mayo Clinic, Rochester, Minn., and her associates.

At the clinic, radioiodine therapy is the first choice of treatment for hyperthyroid adult Graves’ patients, regardless of the presence or severity of ophthalmopathy.

For the study, the investigators reviewed the charts of 592 such patients who had received their first radioiodine therapy between 1990 and 1993.

Most of the patients were women (76.9%), and the group had a mean age of 49 years. The majority (63.2%) had a history of smoking, 45.7% were current smokers, and 19.9% had taken antithyroid medication before being referred to Mayo.

Graves’ ophthalmopathy was present prior to radioiodine therapy in 17.7% (105) of the patients, comprising 21% of the smokers and 14% of the nonsmokers.

The patients with Graves’ ophthalmopathy at baseline had significantly higher levels of thyroid-stimulating immunoglobulin. Those patients also were more likely to have been taking antithyroid medication (36.2% vs. 16.9%), suggesting that the referring physicians were under the impression that radioiodine therapy might have adverse effects on Graves’ ophthalmopathy, the investigators noted.

The rate of new-onset Graves’ ophthalmopathy was 5% in the first year after radioiodine therapy, rising to 19.6% at 10 years, the investigators reported.

Patient survival free of Graves’ ophthalmopathy was 94.9% at 1 year, 86.3% at 3 years, 85.8% at 5 years, and 80.4% at 10 years.

The development of new-onset Graves’ ophthalmopathy was not associated with gender, smoking status, serum thyroxine concentrations, thyroid weight, patient age, or the need for a second dose of radioactive iodine.

However, development of new-onset Graves’ ophthalmopathy was marginally related to higher concentrations of thyroid-stimulating immunoglobulin, the investigators reported.

The purported adverse effects of radioiodine therapy and the increase in thyroid-stimulating hormone receptor antibodies typically occur in the first few months after radioiodine therapy.

The fact that new cases of Graves’ ophthalmopathy occurred in just 5% of study patients in the first year, with the rate remaining steady for the first 3 years, makes it unlikely that radioiodine therapy has an adverse effect on patients who do not already have Graves’ ophthalmopathy at baseline, Dr. Hallanger-Johnson and her associates pointed out.

The study did not address the course of eye disease among the 17% of patients who already had Graves’ ophthalmopathy at baseline, the investigators noted.

Graves’ Disease in Pregnancy

WASHINGTON — Given growing concerns about propylthiouracil-related liver toxicity, “it may be that we should be weighing the relative risks” of this drug and methimazole for the treatment of Graves’ disease during pregnancy, Dr. Susan J. Mandel said.

Propylthiouracil (PTU) has been the preferred therapy for Graves’ disease during pregnancy, especially during first-trimester organogenesis, because methimazole (MMI) and carbimazole have been associated with aplasia cutis and rare embryopathy including choanal atresia, esophageal atresia, tracheoesophageal fistula, and athelia.

None of these congenital anomalies has been reported with the use of PTU, Dr. Mandel said at an American Thyroid Association–sponsored meeting. Dr. Mandel is associate chief of the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia.

Last month, the Food and Drug Administration issued a warning about the risk of severe liver injury associated with the use of PTU with the treatment of Graves’ disease. “After analyzing adverse event reports, the FDA has identified an increased risk of liver injury with propylthiouracil, compared with an alternative treatment for Graves’ disease, methimazole,” Dr. Amy Egan, deputy director for safety, division of metabolism and endocrinology products, FDA Center for Drug Evaluation and Research, said in a statement.

“Health care professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease. If PTU therapy is chosen, the patient should be closely monitored for symptoms and signs of liver injury, especially during the first 6 months after initiating therapy.”

The FDA is advising health care professionals to reserve PTU for patients in their first trimester of pregnancy or those who are intolerant of or allergic to methimazole.

The FDA statement, posted on the agency’s MedWatch Web site, said that 32 cases of serious liver injury were reported to the FDA from 1969, when the agency’s adverse event reporting program was established, through October 2008. Of these cases, 22 were in adults, and included 12 fatalities and 5 liver transplants. Among the 10 pediatric cases, there were 6 reports of liver transplants and 1 fatality, according to the statement.

On the basis of an analysis of these reports, the FDA has determined that the risk of hepatotoxicity is greater with PTU than with MMI. The FDA received only five reports of serious liver injury associated with MMI, which was approved in 1950.

The FDA announced plans to change the prescribing information for PTU to reflect the hepatotoxicity warning

Concerns about PTU’s hepatotoxicity have come largely from the pediatric community. Last year, the National Institute of Child Health and Human Development (NICHD) held a conference on “hepatic toxicity following treatment for pediatric Graves’ disease.” And most recently, Dr. Scott A. Rivkees of Yale University, New Haven, Conn., and Dr. Donald R. Mattison of NICHD called for an end to the use of PTU in children.

In a letter to the editor published in the April 9 issue of the New England Journal of Medicine (2009;360:1574-5), Dr. Rivkees and Dr. Mattison said that PTU-induced liver failure may occur in 1 in 2,000 to 1 in 4,000 treated children, with nearly 10 times that range developing reversible PTU-induced liver injury.

In the context of Graves’ disease in pregnancy, Dr. Mandel said, “it may be that we should be rethinking, what are the relative risks of hepatotoxicity with PTU versus the very rare embryopathy reported with methimazole [and carbimazole].”

Because the changes apparently caused by MMI “all occur by 8-10 weeks’ gestation, and some even earlier, there may be a rationale” to using PTU into early pregnancy and then switching to methimazole afterwards,” added Dr. Mandel, also professor of medicine and radiology at the University of Pennsylvania.

The original recommendations to use PTU in pregnancy–before the teratogenic effects of MMI were reported–came from studies suggesting that PTU was less likely to cross the placenta. More recent data acquired through the use of newer measurement techniques have challenged this, demonstrating a similar degree of transplacental passage with both drugs, she noted.