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VII. MACULAR DEGENERATION

Reading, writing, and all activities that require fine vision are done by the macula. This is a small area located temporally to the optic nerve (Figure 11). Outside this area, the vision of the retina decreases gradually.

Figure 11. Schematic representation of the retina of a right eye. The sinuous black lines represent the retinal blood vessels. The central spot represents the optic nerve. The macula is the stippled area located temporally to the optic nerve.

Vision in the retina depends on specialized cells, the photoreceptors, which are exquisitely sensitive to light. The photoreceptors are of two kinds: the cones which mostly serve for acute vision in the macula, and the rods, which record the dimmer vision in the retinal periphery. The photoreceptors are very active cells and are nourished by a layer of fine blood vessels, called the choriocapillaris. This layer lies close to, but underneath the retina.

Macular degeneration occurs when the photoreceptors of the macula degenerate and die. The mechanism by which macular degeneration occurs is not fully understood. Our best guess today is that the photoreceptors of the macula, being extremely active, do not receive enough oxygen from the choriocapillaris. The following is what we understand of the detailed mechanism of this process.

Mechanism of Macular Degeneration

If we look under the microscope at an ultra thin cross-section of the normal macula, we see that the photoreceptors sit on a layer of pigment cells, called the retinal pigment epithelium, (RPE). The very active photoreceptors must be continuously supplied by new light-sensitive material. Used light-sensitive material is continuously absorbed by the pigment epithelium and recycled to be re-used again. This process requires oxygen and other food supplied by the fine blood vessels of the choriocapillaris.

When the renewal process of the photoreceptors fails, the photoreceptors die and so also does the pigment epithelium. This is called the dry form of macular degeneration. Sometimes, the photoreceptors and pigment epithelium send a distress signal to the choriocapillaris, because they need more oxygen. As a response, the choriocapillaris attempts to make new vessels that should supply more oxygen to the photoreceptors. However, the new vessels have defective walls and tend to bleed, making the case worse. This is called the wet form of macular degeneration. In the breakdown of the macula, we don’t know what breaks first: the photoreceptors, or the photoreceptors repair shop which is the pigment epithelium.

How is Macular Degeneration Diagnosed?

At the early beginning, the patient may notice a dimming of his/her vision. Often, however, there is little or no dimming of vision but the retina specialist sees abnormal deposits in and around the macula , called drusen. (figure 12) Drusen are the first sign of early macular degeneration. They are abnormal deposits under the retina, which are often only partially visible and may cause the patient to see objects distorted. Straight lines may look bent. Later the drusen multiply and may become pigmented, and the macula may become atrophic. A good way for the patient to detect a bend in straight lines is to use the Amsler Grid. This is paper with a grid of vertical and horizontal lines (figure 13). 

Figure 12. Photograph of a retina after injection of a green dye in the patient’s vein. At left is part of the normal optic nerve. The blood vessels of the retina stand out because they contain green dye. The darker central spot is the macula. The somewhat irregular whitish spots are drusen. Their presence indicates early dry macular degeneration.

Figure 13. Amsler grid.

This is how to use the Amsler grid:

1. Wear your reading glasses

2. Cover one eye.

3. Look at the center dot of the Amsler Grid and keep your eye focused on it at all times.

4. While looking directly at the center and only the center, be sure that the lines around the center are straight.

5. If you notice an area on the grid that is distorted, please call your eye doctor.

6. Do this test for each eye separately.

If the Amsler Grid appears distorted to you, it indicates that there is a problem with your macula. However, this is not necessarily dry macular degeneration since other conditions may cause distortion of the Amsler Grid.

The dry form of macular degeneration represents about 90% of all cases, and the wet form affects 10 to 15% of the cases. In order to determine if you have macular degeneration and what form, the doctor will measure your vision and examine your eyes. By looking at the retina, the doctor will tell you if drusen are found. In this case, you should schedule regular check-ups to evaluate changes in the degree of damage to your retina. It may be necessary to take photographs of each macula in order to compare the photos with future examinations.

Dry or Atrophic Macular Degeneration

As we have already mentioned, drusen indicate the presence of dry macular degeneration. Drusen may not cause visual trouble to the patient until they multiply, become pigmented and cause gradual retinal atrophy.

A very important way to examine the patient with dry macular degeneration is the Scanning Laser Ophthalmoscope (SLO). This instrument was invented by the clinical researches working with the Schepens Retina Associates Foundation. It permits us to study a magnified image of the macula. It measures the patient’s vision accurately. It determines exactly what portion of the macula is sick and what area is still healthy and functions well. The SLO is only available in very few eye clinics in the world.

Treatment. Until now, there is no medical or surgical treatment that can cure dry macular degeneration. However, a diet rich in fresh fruit and vegetables and certain vitamins can help in slowing down or arresting the process. (See Lifestyle Changes).

The next step for the patient is to make maximum use of his/her remaining healthy retina. The SLO is very important to find where the remaining healthy retina is located. A specialist in low vision aids can prescribe appropriate lenses that aid reading or seeing far away. Electronic devices are also available. They exist either as a Closed Circuit Television (CCTV) which rests on a desk (Figure 14) or as a miniaturized device that can be worn on the patient’s head (Figure 15).

The dry form of macular degeneration can change into the wet form. Therefore, regular checkups are important.

How is Wet Macular Degeneration Diagnosed?

Wet macular degeneration occurs when new vessels develop under the macula (See Mechanism of Macular Degeneration). These new vessels have poorly developed walls and often leak fluid and frank blood under the retina, thus creating a swelling under the macula. Since it is important to visualize these new vessels with precision, they are made more visible by a special technique, called fluorescein angiography. The doctor injects an innocuous green dye in a vein of the patient’s arm. The dye circulates in all the vessels of the patient’s body. When it enters the vessels of the eye, a series of photographs are taken. They can be studied under magnification (Figure 16).

Figure 16. Photograph of a retina showing wet macular degeneration. To the left is the normal optic nerve. The retinal blood vessels show prominently after an intravenous injection of dye. The hazy black spot in the center is the macula. The irregular white spot, around  the larger part of the macula, indicates the presence of leaky new vessels, under the retina. The large crescentic whitish spot, below the macula, indicates swelling of the retina, resulting from fluid that leaks from the new vessels.

Surgical Treatments

So far, no treatment exists to cure wet macular degeneration.  However, the condition can be alleviated both medically and surgically.  The medical treatment is essentially similar to that used in dry macular degeneration (see Lifestyle Changes).

The surgical treatment generally practiced consists of two ways to use a laser.  In the first way, one destroys the newly formed vessels with the laser.  The second way to use a laser is by applying Photodynamic Therapy (PDT).  In this technique, a special photosensitive dye (Verteporfin) is injected in a vein of the patient.  This special dye penetrates preferentially the walls of the new vessels.  Subsequently the patient’s retina is exposed to a relatively weak laser light which burns the new vessels that have absorbed the dye avidly.  The result is that new vessels are closed but most regular vessels remain open.  PDT treatment has maintained or improved the vision of about 60% of treated patients.  This treatment may need to be repeated to be permanently effective.  However, when the PDT treatment is repeated, some of the normal vessels become also affected by the green dye and the blind area resulting from treatment becomes enlarged.

Lifestyle Changes

Several changes in lifestyle have proven beneficial to patients with either wet or dry macular degeneration.

Avoiding excessive sunlight

Maintaining physical fitness

Avoiding tobacco and excessive alcohol consumption 

Eating a diet rich in vegetables, fresh fruit and fish, and low in fats and red meat.  A recent study sponsored by the National Eye Institute at the National Institutes of Health found that eating vegetable fats, either monounsaturated or polyunsaturated, and linoleic acid was directly associated with the risk of developing advanced macular degeneration (highly processed, store-bought snack foods and fast foods like potato chips and french fries contain a lot of these fats).  Diets high in cholesterol are also contraindicated.  In contrast, intake of omega-3 fatty acids and fish seem to have a protective effect, although only in individuals with low linoleic acid levels. 

Vitamins C and E supplements are strongly recommended.  A recent study conducted by the National Eye Institute confirmed this. 

Selenium supplementation has also been recommended, although selenium’s potential side-effects make this a less desirable option. 

Several carotenoids appear effective as macular degeneration preventives, particularly lutein and zeaxanthin, which are mostly concentrated in dark green leafy vegetables such as spinach, kale, and collard greens.  Beta carotene is also said to be effective, even though it does not penetrate into the retina.

Less Frequent Surgical Treatments

Two other surgical treatments have been tried.  One is the surgical removal of the underlying layer, or scar produced under the retina, by the wet macular degeneration.  This treatment seldom produces rewarding results.  The other is the macular translocation in which the macula is surgically moved away from the damaged underlying layer or scar.  This operation is being tried in some cases of dry or wet macular degeneration. Evaluation of its usefulness and complications need further research.

Transpupillary thermotherapy treatment (TTT) uses infrared light to focus moderate heat on the retinal lesion caused by wet macular degeneration.  This type of treatment has been championed by Dr. Trempe for several years without using infrared light.  Dr. Trempe repeatedly applies a low-intensity 100-mw green laser to the entire lesion for periods of 10 to 15 seconds, for a total treating time of 100 to 200 seconds.  This allows a more even distribution of heat in the treated area, causing less damage around the macular area than the high-intensity, very short duration treatment still used routinely by most surgeons. 

Using a weak laser to treat early dry macular degeneration is still experimented with.  One approach uses a weak argon laser to cause barely visible spots of reaction around the macula.  This has produced controversial results because the laser marks, which were initially small and weak, often enlarge considerably over the years.

Experimental Procedures

Recent research has focused on using retinal cell transplants to create function in the macula.  Studies conducted during the past decade have shown that retinal cell transplants remain viable in animals for up to 6 months.  In human studies, researchers have tried removing the new, abnormal, subretinal vessels and transplanting early fetal retinal pigment epithelium beneath the macular retina.  They have also tried implanting autografts of iris pigment epithelium.  Unfortunately, these surgical attempts have not yet produced durable postoperative visual improvement. 

Researchers in the United States, Japan, and Europe are currently experimenting with retinal prostheses, implanting chips to replace non-functioning retinal rods and cones in patients who are totally blind but still have the necessary neural “wiring” for vision, such as many patients affected by profound macular degeneration or retinitis pigmentosa.  The miniaturized chip may be placed either on the macula or under it; some researchers are experimenting with placing the chip directly on the brain.  For now, the procedure (if successful) is only expected to give the patient gross visual perception.  Researchers have not yet conducted extensive human trials with retinal chips.  The main problem has been uncertainty about the long-term tolerance of the retina or brain for the chip, because silicon-based materials can be toxic and react unfavorably with fluids in the eye.  Scientists at the Space Vacuum Epitaxy Center in Houston are now experimenting with thin, photo-sensitive ceramic films that do not have this disadvantage.

Transplants of embryonic retina in special animals can be made to grow well in the receiver eye.  These transplants have been studied in the laboratory for over 15 years.  This type of transplantation is not applicable to humans.  So far these transplants have not grown a connection with the recipient brain, thus making the transplant non-functioning.

Treatments involving electrical microcurrent stimulation, shark cartilage and rheotherapy (blood filtration) are still in use, despite a lack of evidence that they cause improvement.  Treatments involving thalidomide, interferon, X-ray radiation and the proton beam have been largely abandoned due to a lack of demonstrable improvement or too much collateral damage.

Hope for the Future

In the long fight to conquer blindness caused by macular degeneration, we are beginning to see light at the end of the tunnel.  No one can say for sure how soon these conditions will be effectively prevented and cured, but today, final victory looks more reachable than ever.

The infection connection.  Various types of chronic systemic infections can result in subretinal neovascularization in younger individuals; similar types of chronic systemic infection could also play a significant role in dry macular degeneration.

Sometimes, degenerative or hemorrhagic macular changes are observed in subjects who are either relatively young or who show a total absence of drusen and other signs of early macular degeneration.  These patients often display signs of a chronic type of systemic infection.  In all such cases, the patient’s blood tested positive for such agents as Lyme disease, Chlamydia pneumoniae, toxoplasmosis or other infectious agents associated with subretinal neovascularization in younger individuals.  Anecdotal evidence indicates that an appropriate oral antibiotic improves both the general condition and the status of the retina.

Genetic treatments.  Genetic factors involved in macular degeneration are probably multiple and may interact with each other, complicating research.  Nevertheless, we should expect important developments from this source in the future. 

Use of stem cells.  Efforts have been made to develop a retinal transplant from stem cells.  These are embryonic cells that lie dormant in various organs of human and animal subjects.  When placed in the proper medium, stem cells grow retinal cells that seem able to connect with the recipient brain.  At the present time, this is one of the best surgical hopes we have of growing new retina and of curing macular degeneration.

Several pharmacological attempts are currently made to develop a medication that will interfere with the tendency of the eye to produce deficient new vessels in an attempt to remedy the need of the retina for additional oxygen.  It should be remembered that the tendency of tissues to remedy a need of oxygen is a fundamental need of all living tissues.  Without the ability of our tissues to repair even the smallest wound or a minute need for additional oxygen, we would soon die. 

Therefore through eons of time, nature has developed many means to repair wounds or the need for more oxygen.  We must therefore expect that if we interfere with this system, nature has many ways to counter our efforts, and consequently, we are not likely to succeed.