What is Age-Related Macular Degeneration?
The retina is a sheet of light-sensitive tissue on the inner back surface of the eye. It contains specialized cells called photoreceptors that convert light into electrical signals for transmission of images to the brain. The macula is a small, centralized area of the retina which is responsible for acute central vision. Age-Related Macular Degeneration (AMD) is a degenerative retinal disease which typically strikes adults in their fifties or early sixties just when they are beginning their golden years. It progresses painlessly, gradually destroying the central vision needed to read and to write, to drive and to watch TV. As it advances, AMD limits a person’s mobility and devastates their sense of independence and security.

AMD continues to be the number one cause of severe visual impairment and irreversible vision loss among senior citizens in the United States. A recent study by The Eye Diseases Prevalence Research Group found that 1.75 million US citizens 40 years and older have advanced AMD. In addition, more than 7 million Americans are at high risk of developing advanced AMD. By year 2020, almost 3 million Americans will have advanced AMD, due to the rapid aging of the US population. Thus, the increasing burden of legal blindness associated with the “graying” of America presents a significant national health problem.

Who is at risk for AMD?
A number of risk factors for AMD have been identified. These include (Formatted bullets)

• age. Age is by far the single most important risk factor for AMD.
• cardiovascular disease. AMD is more common is persons who have high blood pressure, vascular disorders and/or arteriosclerosis.
• cigarette smoking. Smokers are much more likely to have AMD than nonsmokers, and the higher the level of smoking the greater the risk.
• race. Caucasians are at higher risk than African-Americans, Hispanics or Asians.
• gender. Women are at higher risk than males.
• diet. AMD is significantly higher in persons who have high intakes of saturated fat and cholesterol. Studies also suggest that diets rich in vegetables may be associated with fewer cases of AMD.
• excessive sunlight exposure. Excessive sunlight exposure is known to cause cataracts and may contribute to AMD.
• family history. There is increasing evidence that AMD may be inherited.

Two Types of AMD
There are two types of AMD: dry, or non-neovascular, AMD; and wet, or neovascular, AMD. Dry AMD accounts for approximately 90% of all cases. Clinical examinations of patients with dry AMD show multiple yellow spots or drusen, which are accumulations of lipid rich deposits underneath the retinal pigment epithelium in the macula. (The retinal pigment epithelium or RPE is a layer of cells that lies between the retina and the choroid and nourishes the photoreceptor cells. The choroid is the layer of major blood vessels of the eye.) The buildup of drusen advances slowly and, in the final stages, causes atrophy of the macula and the underlying retinal pigment epithelium.

The exact origin of drusen is unknown, but because they contain lysosomal and cytoplasmic debris from RPE cells, it is currently thought that vision loss from AMD may be the final result of a series of events that begins in the retina pigment epithelium.

Some patients with the early form of dry AMD have excellent visual acuity and no symptoms. However, a significant proportion of patients in the early stages have good visual acuity but difficulty with reading and seeing in dim or darkened lighting. Other common symptoms of early AMD include blurred vision and distortion of straight lines.

Wet AMD is caused by the abnormal growth of blood vessels from the choroid underneath the macula (neovascularization). These new blood vessels leak blood and fluid, which destroy the macula and sometimes cause retinal detachment. The onset of wet AMD can occur fairly quickly, often in a matter of weeks, and it can progress to severe vision loss or blindness within a couple of years.

Treating Dry AMD
At the present time there is no cure for dry AMD. Results from nutritional studies suggest that diets rich in vitamins, minerals and antioxidants may be associated with fewer cases of AMD. The National Eye Institute held a large-scale clinical trial, the Age-Related Eye Disease Study (AREDS). The purpose of the study was to determine the benefit, if any, of antioxidants and zinc on AMD. The following antioxidants were given to study participants: vitamin C (500 mg), vitamin E (400 IU); zinc (80 mg); and copper (2 mg). Results from the study found that for persons with intermediate stage AMD, there was 25 % reduction of risk for their developing advanced stage AMD. Their risk of vision loss was also reduced by 19%. The study found that there was NO benefit for persons with early stage AMD or those who did not have AMD. The study also found that the antioxidants and zinc did not appear to have any effect on the development of cataracts.

The Age-Related Eye Disease Study 2 (AREDS2) is a new study to evaluate whether lutein, zeaxanthin, and omega-3 long-chain polyunsaturated fatty acids (Docosahexaenoic Acid [DHA] and Eicosapentaenoic Acid [EPA]) can help prevent or slow down the progress of age-related macular degeneration. Researchers also want to learn if nutrients have effects on the development of cataracts.

Laser Therapy for Drusen (LTD) is a new treatment for dry AMD that is currently undergoing evaluation in several clinical trials. In these trials, researchers are seeking to determine whether low-intensity laser treatment of drusen will slow the progression of dry AMD. The idea is that a light application of laser seems to activate cells in the eye to clean out the deposits of drusen. These five-year studies, called the Complications of AMD Prevention Trial and Prophylactic Treatment of AMD, are among the first clinical trials testing treatments for dry AMD.

Treating Wet AMD
Patients with wet AMD can be treated with laser photocoagulation to seal the leaking blood vessels. Multiple treatments are often necessary. Because the laser also damages healthy tissue surrounding the blood vessels, there is always some vision loss caused by this treatment. However, without treatment, wet AMD results in a complete loss of central vision.

Photodynamic therapy is another type of laser therapy for wet AMD. A photoactive drug, Visudyne, is administered intravenously and activated by laser light from a low-intensity (“cool”) laser, which activates the laser-sensitive agent in the dye and destroys the abnormal vessels. Since photodynamic therapy does not produce heat like a regular laser, it won’t burn the retina. Multiple treatments are often necessary. Photodynamic therapy will not reverse any lost vision but, for persons just developing wet AMD, it can reduce the risk of further vision loss.

Lucentis and Macugen are antiangiogenic drugs designed to prevent the growth of new blood vessels in wet AMD and diabetic retinopathy. Alcon Laboratories and Bausch & Lomb are also testing a new drugs to prevent blood vessel growth in the eye. All of these drugs must be injected into the eye.

Antiangiogenic drugs are not designed to treat persons with long standing vision loss from wet AMD because the leakage from the abnormal blood vessels causes scarring and deterioration of macular cells; and once cells are lost, they cannot be revitalized. Other research is going on to see what can be done about replacing damaged retinal cells. This includes transplants and retinal implants.

Retinal Transplants and Implants
Retinal cell transplantation studies in animals suggest that transplanting retinal pigment epithelial cells may slow or halt the progression of AMD. But safety studies in patients with AMD found that patients have had immune responses from donor cells. Current research is underway to develop methods to overcome these complications. A recent study has found that transplanted photoreceptor cells restored vision in a rodent model with retinal degeneration. This finding shows that transplanted photoreceptor cells can form nerve connections with the host retina. Much more work remains to be done before it is tried in humans.

Retinal translocation surgery is a new treatment for wet AMD that partially detaches and relocates the macula away from the area of abnormal blood vessel growth. A clinical trial to evaluate this highly experimental treatment is currently underway.

The goal of the Retinal Implant Project is to develop a microelectronic prosthesis to restore some vision to patients with retinal disease. A 60 electrode microarray has been designed to be mounted on the retina and stand in for damaged retinal cells. The person with the implant would wear a miniature electronic camera mounted in a unit resembling glasses. The camera would transmit images to the chip via a receiver implanted behind the ear. The chip would then produce electrical signals that could be transmitted to the brain and interpreted as vision. Currently there are two FDA approved studies to evaluate this device.

The Artificial Silicon Retina is a round microchip 2mm in diameter with 5000 microscopic solar cells. It is implanted in the retina where its job is to receive light from images and transform it into electrochemical impulses that stimulate the remaining functional cells in the retina. The artificial silicon retina is designed for persons who still have some functioning retinal cells, that is, persons with AMD, retinitis pigmentosa, or other retinal degenerative diseases. To date there has been only one pilot study to test for safety and feasibility; six patients who were legally blind from retinitis pigmentosa participated. There were no signs of infection, rejection, detachment of the retina, or moving of the device. However, recovery of visual function was varied: some could see faces, some hand motions, and one who hadn’t been able to see even light could see light. Much work remains to be done on this device.

Low Vision Rehabilitation
Low Vision Rehabilitation focuses on helping patients with AMD find ways to maximize their remaining vision. It has helped thousands of AMD patients to maintain their independence and enhance their lifestyle. Among the low vision aids available to patients with AMD are special lenses and prisms; microscopes and telescopes; filters; non-optical devices such as talking clocks and wristwatches; electronic vision enhancers; and computers. Learning to use low vision aids requires patience and practice. Patients with AMD should consult with an eye care professional or low vision clinic that specializes in the selection and use of low vision aids.

What is amblyopia?
Also known as “lazy eye,” amblyopia is one of the most serious and most common threats to a child’s vision. Amblyopia is reduced vision – uncorrectable with glasses – in an eye that has not received adequate use during infancy or early childhood. There is no visible anatomical defect. Amblyopia affects about 3% of children in the United States.

What causes amblyopia?
Amblyopia has several causes. It can result from one eye being far-sighted and the other near-sighted. It can also result from a misalignment of a child's eyes, such as crossed eyes (strabismus), or from eyelid abnormalities, including ptosis (droopy lid) and hemangioma (elevated red lesion on the lid). In all cases, one eye becomes stronger as the brain blocks the image from the other eye.

Why is early detection important?
If amblyopia is not detected and treated in early childhood, the child may never learn to use the affected eye properly. Treatment may lead to some improvement in vision at any age but early detection and treatment offer the best outcome. If not detected and treated early in life, amblyopia can cause a permanent loss of vision and loss of stereopsis (two eyed depth perception).

Isn’t strabismus the same thing as lazy eye?
No, lazy eye is amblyopia, which is reduced vision in one eye, but strabismus is misalignment of the eyes. It can be confusing because strabismus can cause amblyopia. If a child constantly prefers to use one eye while the other eye turns in all of the time, the brain blocks the images from the eye that is turned in and vision is reduced in that eye.

What treatments are available?
Before treating amblyopia, it may be necessary to first treat the underlying cause with glasses or surgery. Once the underlying cause is corrected, vision can be improved by patching or medication. In patching therapy, one eye is covered with an eye patch part of each day, for a period of time ranging from a few weeks to more than a year. The better-seeing eye is patched, forcing the "lazy" one to work, in order to strengthen its vision. Alternatively, eye drops or ointment can be used to blur the vision of the good eye in order to force the weaker one to work.

What is a cataract?
A cataract is an opacity in the lens of the eye. The lens sits behind the pupil and focuses light into the eye. The lens is normally crystal clear. If it is a small cataract, it may look like just a small cloudy spot in the middle of the pupil. These small cataracts do not usually have an impact on vision. Other cataracts can make the entire lens cloudy and prevent the lens from focusing images into the eye.

Congenital cataracts can be present in infants and small children and are almost always diagnosed by a pediatrician during the first few weeks or months of life. The pediatrician usually refers the child to a pediatric ophthalmologist for treatment. Cataract surgery is usually recommended very early in life, but this decision will depend on many factors, including the child's overall health and whether there is a cataract in one or both eyes.

What causes cataracts in infants and young children?
Cataracts in infants and young children may be associated with a number of diseases and syndromes. Most often, there is no identifiable cause, or the cataract is inherited through a dominant gene. The dominantly inherited type of cataract is almost always present in both eyes.

Cataracts in newborns
In a newborn infant, a dense cataract deprives the immature visual system of the stimulation it needs to develop normally. Removal of the cataract via surgical extraction of the lens is the most effective means of treatment for this type of cataract. After surgery, optical correction with a contact lens, glasses, or an intraocular lens replaces the focusing power of the lens that was removed from the eye. Detection of a dense congenital cataract during the first few weeks of life is important because a clear vision is essential for early visual development. If the cataract is present in only one eye, visual rehabilitation depends on patching the healthier eye for several hours a day in early childhood. By covering the good eye after the cataract is removed, the brain is forced to use the eye that had a cataracts and thus re-start the vision development that was delayed while the brain was relying on the good eye. If the cataract is not removed early, the brain may fail to learn to use the eye and permanent visual impairment results.

What is Cone-Rod Dystrophy?
The retina is a sheet of light-sensitive tissue on the inner back surface of the eye. It contains specialized cells called photoreceptors that convert light into neural signals. There are two types of photoreceptor cells: cones for seeing in bright light and rods for seeing in low light. Any disease that results in photoreceptor cell death will lead to blindness. There is a large group of inherited retinal degenerations, due to mutations in many different genes, that are associated with loss of photoreceptor cells. These include retinitis pigmentosa (RP), Stargardt's macular degeneration, and cone-rod dystrophy.

Cone-Rod Dystrophy (CRD) is a progressive retinal degenerative disease that causes deterioration of first the cones and then the rods in the retina and frequently leads to blindness. Like retinitis pigmentosa, cone-rod dystrophy can be inherited as an autosomal dominant or autosomal recessive trait. In its most common form, however, it is usually inherited as an autosomal recessive trait.

What are the symptoms of Cone-Rod Dystrophy?
The earliest symptom of cone-rod dystrophy is decreased visual acuity. At first, patients may be suspected of having Stargardt's macular degeneration. However, the diagnosis of cone-rod dystrophy is usually established with loss of the peripheral visual fields. Cone-rod dystrophy is distinguished from retinitis pigmentosa (RP) by the absence of night blindness as a presenting symptom.

Although cone-rod dystrophy has not been studied to the same extent as retinitis pigmentosa, recent progress has been made in defining the functional changes that lead to vision loss in cone-rod dystrophy patients. In a large prospective study of 100 patients with either cone-rod dystrophy or RP, it was shown that the rate of rod ERG loss was significantly lower in cone-rod dystrophy than in RP. Moreover, the rate of rod loss in cone-rod dystrophy was comparable to the rate of cone loss. This is quite different from RP, where rod function is lost approximately three times faster than cone function (Birch and Anderson, 1993). In other work researchers have shown that the patterns of visual field loss (Birch and Anderson, 1990) and ERG loss (Birch and Fish, 1987) are different in CRD and RP. In summary, cone-rod dystrophy is a clinically distinct inherited retinal degenerative disease with involvement of both cone and rod photoreceptor cells.

Genetic Research into Cone-Rod Dystrophy
The CRX gene, which resides on chromosome 19, has been shown (Cell, November 1997) to contain mutations that cause an autosomal dominant form of cone-rod dystrophy. This genetic form of the disease is clinically known as CORD2 (cone-rod dystrophy 2). The CRX gene encodes a protein that regulates the development of embryonic photoreceptor cells during the early stages of life. Mutations in the CRX gene interfere in this process creating abnormal photoreceptor cells with reduced function. Further study is needed to determine why these abnormal cells experience premature degeneration and death. Although there may be some variability in the clinical course of the disease, previous studies of patients thought to have CORD2 have found that central vision loss begins in the first decade of life with the onset of night blindness occurring sometime after age 20. Little visual function remains after the age of 50.

The ABCR gene has been shown (Cremers et.al., 1998) to be responsible for some forms of autosomal recessive cone-rod dystrophy. It has also been shown to be involved in the related blinding disease, Stargardt's macular degeneration. Researchers at the RFSW in collaboration with Dr. Gabriel Travis at UT Southwestern Medical School have found that ABCR gene mutations cause a defect in rod outer segment function that results in a major lipofuscin accumulation in the retinal pigment epithelium (RPE), which nourishes the photoreceptor cells. This build-up in turn leads to dysfunction or death of the photoreceptors (Cell, July 1999). If researchers can discover methods to inhibit the lipofuscin build-up, new treatments for cone-rod dystrophy may be possible.

At the present time there are no known treatments or cures for cone-rod dystrophy. It has been shown that the ABCR knockout mice that were raised in total darkness exhibited no build-up of lipofuscin. This suggests that patients with cone-rod dystrophy could slow the progression of their blindness by wearing sunglasses and avoiding bright light.

What is infantile nystagmus?
Nystagmus is an involuntary rhythmic shaking or wobbling of the eyes that begins during the first year of life.

What causes infantile nystagmus?
Nystagmus may be inherited, may be idiopathic (no known cause), or may be associated with a sensory problem. In all cases, the direct cause of nystagmus is instability in the motor system controlling the eyes.

How does infantile nystagmus affect my child’s vision?
Decreased vision in infantile nystagmus results from the inability to maintain a stable line of sight. In addition, decreased vision may result from abnormal visual experience during the first years of life. If a child has nystagmus during the critical early years of visual development, the image of the outside world that is transmitted from the eye to the brain is smeared and blurred by the constant motion of the eyes. As a result, the visual areas of the brain may not receive the stimulation that they need to develop properly. Retinal or optic nerve abnormalities that may accompany infantile nystagmus may further degrade vision.

Children with nystagmus have a permanent visual impairment that is uncorrectable by glasses (typically, in the range of 20/40 to 20/200 vision).

What effects will nystagmus have on my child’s daily life?
Nystagmus affects different children in different ways. Here are some common things that you may notice:

• Glasses or contact lenses do not “cure” the nystagmus but they may help to reduce the amount of shaking or wobbling.
• The angle of vision is important. Many children develop a null point -- a position of the eyes where the shaking is minimized. Children with a null point often adopt a head posture that lets them make the best use of their vision. It usually is not helpful to have the child sit off to the side of the television or blackboard. It is much more effective to have the child sit directly in front and turn the head to achieve the null position.
• Children may see small pictures and print in books better if they are allowed to hold the book close to them.
• Some children with nystagmus may benefit from special lighting conditions. Talk to your eye doctor about your child’s specific needs.

What is Leber Congenital Amarosis?
Leber congenital amaurosis (LCA) is an inherited retinal degenerative disease characterized by severe loss of vision at birth. A variety of other eye-related abnormalities including roving eye movements, deep-set eyes, and sensitivity to bright light also occur with this disease. Children with LCA account for 10-18% of all cases of congenital blindness

What are the symptoms?
Individuals with LCA have very reduced vision at birth. Within an infant’s first few months of life, parents usually notice a lack of visual responsiveness and unusual roving eye movements, known as nystagmus. Although the retina may appear normal, electroretinography (ERG) testsdetect little if any activity in the retina. ERG tests are key to establishing a diagnosis of LCA.

Some patients with LCA are also extremely sensitive to light (photophobia). Many children with LCA habitually press on their eyes with their fists or fingers. This habitual pressing on the eyes is known clinically as oculo-digital reflex. The eyes of individuals with LCA also usually appear sunken or deep set. Keratoconus (cone shape to the front of the eye) and cataracts (clouding of the lens, the clear, glass-like structure through which light passes) have also been reported with this disease.
In some cases, LCA is associated with central nervous system complications such as developmental delay, epilepsy, and motor skill impairment. Because LCA is relatively rare, the frequency of central nervous system complications is unknown.

Is it an inherited disease?
LCA is most typically passed through families by the autosomal recessive pattern of inheritance. In this type of inheritance, both parents, called carriers, have one gene for the disease paired with one normal gene. Each of their children has a 25 percent chance (or 1 chance in 4) of inheriting the two LCA genes (one from each parent) needed to cause the disorder. Carriers are unaffected because they have only one copy of the gene. At this time, it is impossible to determine who is a carrier for LCA until after the birth of an affected child.

Are there any other related diseases?
Initially, LCA can be confused with early onset retinitis pigmentosa (RP), congenital and hereditary optic atrophy, cortical blindness, congenital stationary night blindness, flecked retina syndrome, and achromatopsia. Although similarly named, LCA should not be confused with Leber optic atrophy. In addition, there are syndromes seen in infancy where visual impairment is a component. A thorough ophthalmologic examination including diagnostic tests measuring retinal function and an accurate documentation of family history can distinguish between these related conditions.

What treatment is available?
Scientists have identified 14 genes with mutations that can each cause LCA. These genes account for approximately 75 percent of all cases of LCA. With this information, scientists are better equipped to develop preventions and treatments.
Clinical trials of gene replacement therapy for LCA caused by mutations in the RPE65 are now beginning. It is the same therapy that gave vision to 50 dogs, including the world-famous Lancelot, born blind from LCA. These studies provide extraordinary promise for eradicating LCA caused by RPE65, and eventually, LCA caused by other genetic variations.
Some individuals with LCA, who have remaining vision, may also benefit from the use of low-vision aids, including electronic, computer-based and optical aids. Orientation and mobility training, adaptive training skills, job placement, and income assistance are available through community resources.

What is Retinitis Pigmentosa?
The retina is a sheet of light-sensitive tissue on the inner back surface of the eye. It contains specialized cells called photoreceptors that convert light into electrical signals for transmission of images to the brain. There are two types of photoreceptor cells: cones for seeing in bright light and rods for seeing in low light. The cones are concentrated in a small central area of the retina called the macula and are responsible for our acute central vision and our color vision. The rods surround the macula and are responsible for our night-vision and our peripheral (side) vision.

Any disease that results in photoreceptor cell death will lead to blindness. There is a large group of inherited retinal degenerations, due to mutations in many different genes that are associated with loss of photoreceptor cells. One of the most devastating of these diseases is retinitis pigmentosa (RP). RP can be inherited as an autosomal dominant, autosomal recessive, or X-linked trait. (Autosomal means that the gene is located on one of the 22 pairs of chromosomes that are identical in men and women; X-linked means the gene is located on the X chromosome that determines the sex). In autosomal dominant RP, only one parent needs to have the defective gene to pass it on to a child (the parent will also have RP). In autosomal recessive RP, both parents must have the defective gene for a child to be affected (the parents will generally not be affected). In X-linked RP, males will have RP and females will be the carriers (sometimes females will be mildly affected).

RP blinds 100,000 to 200,000 people in the U.S. and impacts thousands more as family and relatives struggle to cope with this debilitating disease. It has been estimated that one out of every 80 persons carries a recessive gene for RP although neither they nor their children will ever have the disease.

What are the symptoms of RP?
The first symptom of RP is difficulty in seeing in the dark or in dim lighting due to the degeneration of rod photoreceptors. Loss of night-vision is followed by a progressive loss of peripheral vision which leads to increasing tunnel vision, legal blindness and, eventually, total blindness. At present there is no known cure for this most devastating genetic disease.

Patients with autosomal dominant and autosomal recessive RP are usually diagnosed with RP during early adulthood. Legal blindness for these persons is dependent on the type of genetic inheritance pattern; it occurs most often in the fourth to fifth decade of life. X-linked RP is the most severe form of the disease. Night-blindness begins between 5 and 15 years of age and X-linked RP patients typically become legally blind by their 20s.

Treating Retinitis Pigmentosa
At the present time there is no known cure for RP. The only known “treatment” is nutritional supplementation with vitamin A palmitate. Results from a six-year clinical study reported in June 1993 that patients who took 15,000 IU of vitamin A palmitate had a significantly lower rate (20% per year) of retinal degeneration than patients who did not take this supplement. It is important to note that vitamin A palmitate will not cure RP and that doses higher than 25,000 IU per day may be toxic and can cause lever disease. Because of an increased risk for birth defects, it is extremely important that women not take supplemental vitamin A if there is any chance of becoming pregnant.

Clinical trials are currently underway to see if dietary supplementation with docosahexaenoic acid (DHA) will slow the progression of the disease. Additional research is being done to evaluate the role of antioxidants on RP. It is hoped that additional nutritional treatments will be developed from these studies.

A clinical trial is currently underway using Neurotech’s Encapsulated Cell Technology (ECT) to deliver ciliary neurotrophic factor (CNTF) to eyes of visually impaired patients with retinitis pigmentosa (RP). The device is placed into the vitreous of patients with RP and allows for sustained released of the drug. Preliminary tests showed that CNTF can be safely delivered into the vitreous of patients with RP and that the implants were well tolerated by the patients. In addition some patients experienced improvement in their visual acuity.

Researchers are also working on gene therapy for RP. By delivering healthy genes or genetic information to cells affected by a gene mutation, it may be possible to overcome conditions that cause vision loss.

Retinal Transplants & Implants
Retinal cell transplantation studies in animals suggest that transplanting retinal pigment epithelial cells may slow or halt the progression of RP. But safety studies found that patients have had immune responses from donor cells. Current research is underway to develop methods to overcome these complications.

The goal of the Retinal Implant Project is to develop a microelectronic prosthesis to restore some vision to patients with retinal disease. The project is to develop a light-sensitive diode array that can be mounted on the retina. The person with the implant would wear a miniature electronic camera mounted in a unit resembling glasses. The camera would transmit images to the diode array in the retina. The diode would produce electrical signals that could be transmitted to the brain and interpreted as vision.

Low Vision Rehabilitation
Low Vision Rehabilitation focuses on helping patients with RP find ways to maximize their remaining vision. It has helped thousands of RP patients maintain their independence and has enhanced their lifestyle. Among the low vision aids available to patients with RP are special lenses and prisms; microscopes and telescopes; filters; non-optical devices such as talking clocks and wristwatches; electronic vision enhancers; and computers. Learning to use low vision aids requires patience and practice. Patients with RP should consult with an eye care professional or low vision clinic that specializes in the selection and use of low vision aids.

What is Stargardt Disease?
The retina is a sheet of light-sensitive tissue on the inner back surface of the eye. It contains specialized cells called photoreceptors (rods and cones) that convert light into electrical signals for transmission of images to the brain. The macula is a small, centralized area of the retina which is responsible for our acute central vision. Macular degeneration is a retinal degenerative disease that causes loss of central vision, hindering activities that require fine visual discrimination such as reading, sewing, recognizing faces, watching TV, and driving a car. Stargardt Disease is a severe hereditary form of macular degeneration that begins in late childhood and leads rapidly to legal blindness. It is inherited as an autosomal recessive trait. Stargardt's is clinically similar to age-related macular degeneration and affects approximately one in 10,000 children.

What are the symptoms of Stargardt Disease?
Stargardt's causes a progressive loss of central vision. In the early stages patients may have good visual acuity but difficulty with reading and seeing in dim or darkened lighting (delayed rod dark adaptation). Other common symptoms of Stargardt's include blurred vision and seeing straight lines as crooked. The ophthalmological findings vary significantly with the progression of the disease. In fundus photos (pictures of the retina) patients with early Stargardt appear to have simple macular degeneration. As the disease progresses, multiple yellow spots or lipofuscin, which are accumulations of lipid rich deposits underneath the retinal pigment epithelium in the macula, appear around the macula. (The retinal pigment epithelium is a layer of cells that lies between the retina and the choroid and nourishes the photoreceptor cells. The choroid is the layer of major blood vessels of the eye.). In advanced Stargardt's, the buildup of lipofuscin causes atrophy of the macula and the underlying retinal pigment epithelium (RPE). It was these differences in appearance as the disease progressed that made researchers originally think that Stargardt's was originally two separate diseases: fundus flavimaculatus and Stargardt's macular degeneration (or juvenile macular degeneration).

ABCR Gene and Stargardt Disease
Significant progress has been made in the past three years in uncovering the genetic basis of Stargardt's. In early 1997 researchers showed that the mutations in the ABCR gene are responsible for Stargardt Disease (Allikmets, et al.). More recently researchers at the RFSW in collaboration with Dr. Gabriel Travis at UT Southwestern Medical Center, have generated a mouse model of Stargardt's by "knocking out" the ABCR gene. These ABCR knockout mice show many characteristics of Stargardt's such as lipofuscin accumulation in RPE, delayed rod dark adaptation, and cone cell death. Through these mice, researchers have found that ABCR gene mutations cause a defect in rod outer segment function that results in a major lipofuscin accumulation in RPE, which in turn leads to dysfunction or death of the cone photoreceptors in the macula (Cell, July 1999). These mice will be used to test potential new treatments for Stargardt's, presumably by inhibiting lipofuscin accumulation in RPE. If researchers can discover methods to inhibit the lipofuscin buildup, new treatments for Stargardt's may be possible.

At the present time there are no known treatments or cures for Stargardt's. It has been shown that the ABCR knockout mice that were raised in total darkness exhibited no build-up of lipofuscin. This suggests that patients with Stargardt's could slow the progression of their blindness by wearing sunglasses and avoiding bright light.

What causes the misalignment?
Normally, six small muscles attached to each eye work together to keep the eyes aligned as your child looks around the world. Problems with the eye muscles or the nerves that control them may prevent your child’s eyes from working in parallel. The misalignment results from the failure of the eye muscles to work together. One eye or both eyes may turn in (crossed eyes), turn out, turn up or turn down. Sometimes more than one of the “turns” is present.

If my child has strabismus, will the eyes always be misaligned?
The misalignment may be constant or it may come and go. You may also notice it only when your child is looking at things that are close to him or only when your child looks off at something in the distance.

What should I do if I think that my child may have strabismus?
If you notice that your child’s eyes are not aligned, talk to your pediatrician about whether your child should be examined by a pediatric ophthalmologist. It is critical to diagnose and treat strabismus as soon as possible after its onset. Otherwise, the child may develop amblyopia (lazy eye) and permanently disrupt binocular vision. Prompt medical attention is recommended for another reason, too. Rarely, strabismus may be the first sign that the child has a more serious health problem, such as a tumor.

Isn’t strabismus the same thing as lazy eye?
No, lazy eye is amblyopia, which is reduced vision in one eye, but strabismus is misalignment of the eyes. It can be confusing because strabismus can cause amblyopia. If a child constantly prefers to use one eye while the other eye turns in all of the time, the brain blocks the images from the eye that is turned in and vision is reduced in that eye.

What is pseudostrabismus?
Some children appear to have strabismus but they do not. Pseudostrabismus is the looks like crossed eyes because some infants have a wide fold of skin on either side of the nose or a broad nose bridge. Pseudostrabismus disappears as the face grows. It is easy for a pediatric ophthalmologist to tell whether your child has strabismus or pseudostrabismus.

What is Usher Syndrome?
Usher Syndrome is a genetic disorder with hearing loss and a progressive loss of vision resembling retinitis pigmentosa. Some individuals also have balance problems. There are three types of Usher Syndrome:

Type 1: born with a profound hearing loss, a form of retinitis pigmentosa, and balance problems.

Type II: born with moderate to sever hearing loss, a form of retinitis pigmentosa, and no balance problems.

Type III: hearing loss that gets worse over time, a form of retinitis pigmentosa, and may have balance problems that also seem to get worse with age.

Hearing Loss
Individuals with Type I Usher Syndrome have a profound hearing loss in all frequencies and are considered to be deaf from birth. These persons usually have poor speech. Persons with profound hearing loss may be candidates for cochlear implants.

Individuals with Type II Usher Syndrome have a moderate hearing loss in the lower frequencies. In the higher frequencies it is severe or profound. The loss does not usually get worse as the person ages. These persons are considered to be hard-of-hearing and usually find hearing aids to be useful.

Individuals with Type III Usher Syndrome have a progressive hearing loss that gets significantly worse as the person ages. Most of the documented Type II cases are in Finland.

Retinitis Pigmentosa (RP)
RP is the name given to a group of eye diseases that causes gradual loss of vision. Those affected become less able to see in low light, resulting in night blindness. As RP progresses, the field of vision narrows until only central vision remains. This is called "tunnel vision". Many persons with Usher Syndrome will retain at least some central vision for a long time.

Balance Problems
There are three senses we use to keep our balance: vision (we see where we are), proprioception (we feel the position of our bodies and limbs), and vestibular (we feel changes in speed and direction). The vestibular system is part of the inner ear.

Persons with Type I have a vestibular system that does not work. Persons with Usher Type I usually do not learn to walk until they are between 18 and 24 months old. They cannot feel changes in speed or direction and as their vision decreases, their visual balance system becomes less reliable.

Persons with Type II have a normal vestibular system but their visual system also becomes less reliable as their vision decreases. Persons with Type II usually learn to walk around the age of 12 months.

We don'ts know much about the vestibular system in persons with Type III but we think it gets worse with age. As more information on Type III becomes available, a clearer picture of vestibular function will emerge.

What causes Usher Syndrome?
Usher Syndrome is a genetic condition. Genes carry the "blueprint" for each living thing. When the genes from the mother and father come together in the fertilized egg cell, they arrange themselves in pairs. Genes provide the information that allow this single cell to grow into a human being.

Genes always come in pairs. The pair is made up of one gene from the mother and one from the father. In turn, parents pass only one gene from each pair to each of their children. Which gene the child receives from a parent is determined randomly. Just as when we flip a coin, whether it comes up heads or tails is a random event.

Occasionally, something happens that causes a gene to change. Geneticists call this change a mutation. It is estimated that each of us have several mutated genes. Most mutations have no effect on the individual, but some mutations cause the disease.

In order to have Usher Syndrome, a person must have a mutation in both genes of the pair that can cause Usher Syndrome. A person will not have Usher Syndrome if their pair of Usher genes is made up of one gene that is changed (could cause Usher Syndrome) and one gene that has not been changed. However, this person will be a carrier of Usher Syndrome. It is estimated that about 1 in every 75 people carry an Usher gene, most do no know they carry the gene.

If both mother and father are carriers, they could have children with Usher Syndrome. If the child receives the changed gene from each parent, that child will have a pair of changed genes. When a person has a pair of changed genes, he or she will have Usher Syndrome.

Because a person must have a pair of mutated genes before they develop the syndrome, Usher Syndrome is called a recessive condition. If a person receives only one Usher causing gene and the other gene of that pair cannot cause Usher, that person will not have Usher Syndrome. But, like the parents, that person will be a carrier of Usher Syndrome.

If a person who has Usher Syndrome marries a person who is not a carrier, none of their children will have Usher Syndrome. However, all of their children will be carriers.

If a person who carries Usher Syndrome marries a person who does not, none of their children will have Usher Syndrome. But, there is a 1 in 2 chance that each child will be a carrier.

If two people with Usher Syndrome (caused by the same gene) marry, all of their children will have Usher Syndrome.

If two persons with Usher Syndrome (caused by different genes; for example Usher Type 1b and Usher Type 1d) marry, there is no evidence any of their children will have Usher Syndrome but all of their children will be carriers for both types. In the case of our example, they would each receive one mutation for Type 1b and one for Type 1d.

Dianna Wheaton, a genetic counselor at the Retina Foundation of the Southwest, can provide additional information if you are interested. That information will be tailored to your situation and needs.

What Research is Being Done on Usher Syndrome?
The Retina Foundation of the Southwest is working in conjunction with geneticists at Boys Town National Research Hospital, under the direction of Dr. William Kimberling. Scientists in Dallas, under the direction of Dr. David Birch, are identifying new families with Usher, studying the time course of visual loss, and searching for nutritional and other environmental influences that could slow the rate of visual loss. Scientists at Boys Town in Omaha are conduction studies designed to identify the genes' that cause Usher Syndrome. They now suspect there are at least ten genes that can cause Usher Syndrome. Based on clinical symptoms (hearing loss, RP etc.), there are three types. Usher Type I has six subtypes; Usher Type II has three subtypes; and Usher Type III has only one known subtype.

This research has identified the gene that causes almost half of the cases of Usher Type I. It is on a long arm of chromosome 11 and has been named USH1B. It is responsible for Usher subtype 1b. Although it is now known to be a Myosin VIIa gene, much work remains to be done toward understanding how the gene causes Usher Type I. In the last months of 2000, two additional Usher Type I genes were identified. USH1C is responsible for Usher subtype 1c and is also on chromosome 11. It codes for a protein called harmonin. USH1D is on chromosome 10, and codes for the protein cadherin. How these genes cause Usher Syndrome is currently under investigation. Three additional genes that cause Usher Type I have also been localized. One of the genes is on chromosome 14 and is called USH1A. USH1F has been localized to chromosome 10 and USH1E has been localized to chromosome 21. These three genes remain to be identified.

In 1998, Dr. Kimberling's group identified the gene that causes most cases of Usher Type II. It is called USH2A and codes for a newly identified protein, usherin. Their test results also indicate that another gene exists that causes Usher Type II symptoms. It is called USH2C and has been localized to chromosome 5. USH2B has been localized to chromosome 3. Neither of these genes has been identified.

The gene that causes Usher Type III has been localized to chromosome 3 but remains to be identified.