ARMD Treatment -Haynie

Age-related macular degeneration (ARMD) is the leading cause of legal blindness in those over the age of 65 years (1). It currently affects more than 3.7 million Americans, with the number of new cases increasing rapidly due to the increase in the number of elderly individuals. Risk factors include aging; female gender (ARMD is twice as common in women as in men); systemic hypertension; smoking, which increases risk of vision loss by 30-50%; light complexion; and light-colored irides (2,3).

Regrettably, the end stage of ARMD can be irreversible central vision loss to the level of legal blindness. Although ARMD in and of itself will not cause full-field total blindness, legal blindness may restrict reading, driving, and recognizing family or friends. With the loss of central visual acuity, elderly patients are often stripped of their independence and confined to nursing homes.

This course summarizes the pathophysiology of ARMD and presents a review of current strategies for its management.

The retinal pigment epithelium (RPE) lies between Bruch’s membrane and the sensory retina. In the normal retina, RPE cells have many functions. These include structurally supporting and orienting the receptor outer segments, providing a nutritional interface between the receptors and the choriod, and regenerating photopigments. In addition, the RPE cells digest and recycle receptor outer segment material that they phagocytize. (This process is NOT related to the regeneration of receptor photopigments, which also occurs in the RPE cells).

The RPE decomposition and recycling process is quite efficient in young persons, but it breaks down in some older patients. It is further compromised if the materials that are shed from the outer segments have been damaged by free radicals (molecules with unpaired or lost electrons) that are produced by various processes, including the effects of short-wavelength light (e.g., blue and UV).

Because free radicals easily damage the receptor outer segment membranes, and because damaged materials are hard to decompose and recycle, nature has provided several protective mechanisms for the retina.

The retina is protected by antioxidants, which are molecules that can donate electrons to free radicals thereby quenching them. Common antioxidant vitamins found in the retina are vitamins C and E, and carotenoids such as lutein and zeaxanthin. Other defense systems include antioxidant compounds such as metallationein, melanin, and glutathione; and antioxidant metalloenzymes such as superoxide dismutase and catalase that incorporate the mineral zinc.

Both the lens and the retina also have substances that act as filters to absorb excess amounts of blue and UV light. The lens yellows with age thereby absorbing more blue light, and the retina has the macula lutea pigments lutein and zeaxanthin.

These macular pigments are positioned in the outer plexiform layer of the macula (Henle’s fiber layer) between the incoming light and the photoreceptor outer segments. They act as a filter to reduce the amount of short-wavelength light reaching the receptor outer segments in which phototransduction takes place.

The macular pigments give the foveal area its dark yellow or orange appearance. It was once thought that the pigment was beta-carotene or a closely related substance but now it is known to be composed of the carotenoids lutein and zeaxanthin, which are yellow pigments also found in marigold flowers.

Failure in the RPE cell degradation and recycling system, possibly occurring as a result of free radical damage to molecules within the receptor outer segments, is probably involved in the formation of drusen, the initial lesion seen in ARMD.

In order to understand ARMD, it is necessary to differentiate between its two major clinical forms: dry and wet. The dry form represents almost 90% of individuals with ARMD, whereas the wet form is responsible for nearly 90% of severe vision loss.

Dry ARMD is a progressive condition that begins with the appearance of drusen in the central retinal area.

Drusen are comprised of photoreceptor outer segment products and other materials that are deposited in Bruch’s membrane because they cannot be digested by the RPE cells. If enough drusen accumulate in the membrane, exchange of nutrients between the RPE cells and the adjacent choroidal blood vessels is compromised. As a result, the RPE cells can die and this leads to the death of photoreceptors, which receive their nutritional support from the choroid via the RPE cells.

In teaching optometry students about ARMD and RPE cell functions, a somewhat scatological analogy is sometimes used. Assume that the shedding of outer segment disc membranes and the flushing of solid waste down a toilet are somewhat parallel functions. The discs are decomposed and recycled in the RPE cells, and the toilet waste is decomposed and recycled in a sewage disposal plant. If all products are capable of being completely decomposed, both processes run smoothly.

However, assume that some non-decomposable materials (e.g., pebbles) are flushed down the toilet. When enough of these non-decomposable materials accumulate in the disposal plant, they are hauled away and dumped in a landfill that will eventually be covered over by a mound of dirt.

In the case of RPE cells, the non-decomposable materials, such as molecules damaged by free radicals, accumulate within the cells and are eventually deposited in mounds as drusen.

Dumping non-decomposable material is a good short-term solution for the RPE cells, but, if enough drusen are formed, nutritional compromise can lead to tissue ischemia and cell death. Large areas of atrophy can develop and this leads to the irreversible vision loss produced by dry ARMD.

Management of dry ARMD continues to be a challenge, but several clinical trials have provided some specific guidelines and useful recommendations.

The Age-Related Eye Disease Study (AREDS) (4), sponsored by the National Eye Institute, concluded in 2002. During this large-scale clinical trial, dry ARMD subjects were divided into four groups depending on their level of disease:

Patients in the four groups were randomly assigned to receive supplements with antioxidants alone, the minerals zinc and copper (copper was added to offset the risk of copper deficiency anemia that could be caused by the relatively high level of zinc in the supplement), antioxidants plus zinc and copper, or a placebo.

Few participants in Groups 1 and 2 had ARMD progression during the 5-year course of the study, so their data were excluded from consideration.

Twenty-eight percent of the participants in Groups 3 and 4 who received placebos advanced to more serious ARMD within 5 years, 23% of those receiving antioxidants alone advanced, 22% of those receiving zinc and copper advanced, and 20% of those receiving antioxidants plus minerals advanced (4).

The results of this study indicate that supplementing the diets of patients who have moderate or advanced dry ARMD with antioxidants and minerals could reduce the risk of disease progression by 25% and decrease the risk of vision loss by 19% (4). As a result of this study, many eye care professionals now consider it the standard of care to recommend antioxidant and mineral supplements to their dry ARMD patients.

A more significant question, and one for which there is no current answer, involves whether or not it is appropriate to recommend antioxidant and mineral supplementation as a preventative measure for patients who do not have signs of ARMD. Many doctors believe that antioxidants are generally good for their patients (or at least they cannot hurt), whereas others feel that recommending supplements is not indicated until there is firm evidence supporting their need and efficacy.

To confuse the issue about antioxidant supplementation, the AREDS study was started when lutein, a carotenoid selectively found primarily in the macular area of the retina, was not available as a human dietary supplement. (Beta-carotene, the carotenoid in the AREDS formulation is not found in the retina.)

Even though firm evidence about the efficacy of lutein supplementation in ARMD is lacking, it is now commonly found OTC either alone or in combination with other substances. (In the retina, lutein can be converted to zeaxanthin, the other macular pigment.) Often these supplements are marketed for "vision preservation" and contain 2 - 6 mg of lutein instead of (or in addition to) beta-carotene.

The Lutein Antioxidant Supplement Trial (LAST) investigated the potential benefit of lutein supplementation for 90 patients with dry ARMD(5).

The patients were randomized into three groups: supplementation with 10 mg of lutein per day, supplementation with 10 mg of lutein per day plus other antioxidants, and a placebo group.

After twelve months, the lutein and lutein with other antioxidants groups showed macular pigment density increases of 50% (5). There was also an improvement in glare recovery, contrast sensitivity, and distance/near visual acuity for these patients. Although this was a short-term supplementation study, the results suggest that dry ARMD might be responsive to lutein supplementation.

A larger-scale, randomized control clinical trial looking at lutein supplementation is underway (6). In this trial 6 mg of lutein combined with small amount of Vitamins A, C, and E, zinc, and copper are being given to patients with and without ARMD for 18 months. Outcome measures are distance and near visual acuity, contrast sensitivity, color vision, macular visual field, glare recovery and fundus photography. When completed, this trial should give more information on the use of lutein supplementation for ARMD.

Given that a patient is taking reasonable levels of antioxidant supplementation, there is a wide margin of safety. However, caution should be taken when recommending beta-carotene supplementation to patients who smoke because beta-carotene has been associated with an increased risk of lung cancer in smokers (4).

Large, confluent, soft drusen are associated with a significantly increased risk of choroidal neovascularization (CNV) in which vessels grow beneath Bruch’s membrane, break through from the choroid, and enter the retina causing wet ARMD. An observation that laser photocoagulation can cause drusen to regress suggested that prophylactic laser treatment might reduce or delay the onset of choroidal neovascularization associated with high-risk drusen.

Several clinical trials have been conducted to investigate the efficacy of laser treatment for preventing the conversion of dry ARMD to wet ARMD. The largest of these was the Choroidal Neovascularization Prevention Trial (CNVPT) (7). In this study, large drusen in the fellow eyes of patients with CNV in one eye received either no treatment or grid laser treatment to the macular area.

Early data suggested that the drusen resolved in treated eyes, but they also suggested an increased incidence of CNV development in the treated eyes. Recruitment into the study was halted and follow up was continued only with subjects already enrolled in the study.

When the intensity of the laser burns was quantified, it was found that the higher-intensity prophylactic laser applications were associated with greater drusen reduction (8). Unfortunately, the patients treated with the more intense laser burns were also at greater risk of developing choroidal neovascularization.

The Drusen Laser Study (9) found similar results to those from the Choroidal Neovascularization Prevention Study. The Drusen Laser Study selected patients who had CNV in one eye and large drusen in the other eye. Patients were randomized to receive no treatment or laser treatment in the eye with the drusen. As in the previous study, patients who were treated had an increased risk of CNV development, so recruitment into this trial was also halted.

Another randomized controlled clinical trial, the Complications of Age-Related Macular Degeneration Prevention Trial, is now ongoing (10). In this trial, patients with bilateral large drusen are being treated in one eye with low-intensity laser therapy, with the other eye receiving no treatment. Visual acuity, contrast threshold and critical print size for reading, quality of life and incidence of complications of AMD are being assessed for 5 years. It is possible that this study will show that low intensity laser treatment of drusen can help to prevent CNV development.

Rheophoresis is another potential treatment for dry ARMD (11). It uses a technique in which blood is removed from the patient and the red blood cells are separated from the plasma. The plasma then undergoes a filtration process in which high molecular weight proteins, lipoproteins, and free radicals are removed. The filtered plasma is then recombined with the red blood cells and returned to the patient (11).

Preliminary data show that 30% of rheophoresis-treated patients had acuity improvements of more than three lines on the ETDRS chart, as compared to 5% (1 eye) of the untreated patients (12). Although this trial included only a small number of patients, other studies have duplicated its results. Multicenter clinical trials are ongoing in the United States (MIRA – 1) and Europe (MAC – II) to further evaluate the efficacy of rheophoresis.

Removing high molecular weight proteins and lipoproteins is thought to increase ocular blood flow by reducing blood viscosity. However, these high molecular weight proteins and lipoproteins reappear in the blood within one week, suggesting that rheopheresis may need to be repeated frequently and indefinitely.

In the wet form of ARMD, a choroidal neovascular membrane arises from the choriocapillaris, breaks through Bruch’s membrane, and enters the retina through the damaged RPE. The formation of choroidal neovascularization is responsible for 90% of severe vision loss related to ARMD.

The CNV membrane can leak fluid and red blood cells leading to serous and hemorrhagic RPE detachment, serous and hemorrhagic retinal detachment, and macular hemorrhage. The formation of a disciform scar typically follows these conditions.

Using fluorescein angiography, choroidal neovascularization has been divided into three categories (13). Category one is "predominately classic" (the area of classic neovascularization is greater than 50%) of the area of the entire lesion, category two is "minimally classic" (area of classic neovascularization is less than 50% but greater than 0% of the area of the entire lesion), and category three is "occult with no classic."

Classic CNV is defined in angiographic terms as demonstrating a focal area of hyperfluorescence in the early phase. In the later phase of the angiogram, the borders of the lesion become ill defined and bright hyperfluorescence is noted.

In contrast, an occult CNV shows granular hyperfluorescence in the early phase with late pooling of the fluorescein dye from an unidentifiable focal source.

In a minimally classic CNV, fluorescein shows a large neovascular membrane with an area of focal leakage surrounded by a larger area of hypofluorescence or hemorrhage that prevents visualization of the underlying CNV.

Indocyanine green (ICG) is another fluorescent dye used to evaluate CNV. It has two advantages over fluorescein: the extremely high protein binding of ICG reduces dye leakage from abnormal vessels compared with fluorescein and the infrared fluorescence of ICG penetrates pigment and fluid more readily than the visible-light fluorescence of fluorescein. Because of these properties, both ill-defined and well-defined CNV are more readily observed with ICG angiography. Thus, ICG angiography is valuable in detecting neovascularization, the persistence of neovascularization, and recurrence of neovascularization in ARMD.

There are many treatments for wet ARMD. These include argon laser photocoagulation, photodynamic therapy, macular translocation or subretinal surgery, transpupillary thermotherapy, intravitreal triamcinolone, intravitreal anti-VEGF, and use of intravitreal anti-angiogenic agents.

The current strategies for treatment of a predominantly classic CNV include argon laser photocoagulation, photodynamic therapy, and macular translocation.

Until 2000, management of wet ARMD depended on argon laser photocoagulation of the CNV. Argon laser photocoagulation uses a thermal laser that cauterizes the new choroidal blood vessels, resulting in a chorioretinal scar with obliteration of the neurosensory retina.

The Macular Photocoagulation Study (MPS)(14) demonstrated that photocoagulation effectively prevented large decreases in visual acuity compared to observation without laser intervention. However, no more than 26% of patients with wet ARMD show well-demarcated predominately classic CNV eligible for laser treatment following the guidelines of the Macular Photocoagulation Study. Individuals with minimally classic or occult membranes make up the majority of patients with wet ARMD and were ineligible for laser therapy in the Macular Photocoagulation Study.

Unfortunately, if the CNV involved the foveal area, focal ablation of the lesion resulted in an immediate decrease in visual acuity and a permanent blind area for the patient. Patients with subfoveal CNV who were treated with focal ablation (per the MPS guidelines) initially lost acuity, but the amount of acuity loss in untreated eyes increased to the level of loss in the treated eyes after 12 months and exceeded the level thereafter (14). Even with this information, many doctors were hesitant to treat subfoveal lesions and cause immediate blindness for their patients.

In April 2000, the Food and Drug Administration approved Photodynamic Therapy (PDT) to treat predominantly classic subfoveal CNV in patients with wet ARMD.

Photodynamic Therapy is a two-step process. First, verteporfin (Visudyne), a photosensitizing drug, is infused intravenously over a period of ten minutes and preferentially binds to neovascular tissue in the choroid. In the second step, a low intensity nonthermal laser is focused on the retina overlying the CNV for 83 seconds. The laser light activates the verteporfin and kills the CNV cells. It is believed that the laser converts verteporfin to a triplet state that combines with oxygen to create singlet oxygen, which is primarily responsible for cell death after photodynamic therapy.

In contrast to argon laser photocoagulation, the laser used in photodynamic therapy is harmless in the absence of verteporfin. The energy of the PDT laser is dissipated subretinally, thereby sparing the overlying neurosensory retina. As a result, unlike argon laser photocoagulation that causes a scar, PDT produces no visible scarring.

Results from the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study showed that photodynamic therapy effectively prevented the loss of visual acuity in patients with subfoveal CNV (15). At the 24-month follow up examination, 213 (53%) of 402 verteporfin-treated patients lost fewer than 15 letters of acuity as compared with 78 (38%) of 207 placebo patients.

In a subgroup analysis, for predominantly classic lesions 94 (59%) of the 159 verteporfin-treated patients lost fewer than 15 letters as compared with 26 (31%) of the 83 placebo patients. For minimally classic lesions, no significant differences in visual acuity loss were noted (15).

Verteporfin was well tolerated with only a few ocular or systemic adverse reactions noted. Side-effects that did occur included transient visual disturbances, injection-site adverse events, transient photosensitivity reactions, and infusion-related low back pain (15).

Photodynamic therapy can successfully treat ARMD patients with predominantly classic CNV subfoveal lesions. However, for ARMD patients with subfoveal lesions that are minimally classic, there still is no successful laser-oriented therapy.

In an attempt to preserve vision while treating a subfoveal CNV, other techniques have been developed that spare the neurosensory retina, thus potentially limiting the risk of a dense scotoma.

Macular translocation surgery was pioneered by Eugene deJuan as a method of treating subfoveal CNV (16). The procedure involves surgically moving or translocating the retina so that the CNV is no longer directly beneath the fovea. After the fovea has been translocated, the CNV can be treated with laser therapy while sparing the foveal neurosensory retina.

To accomplish macular translocation, the retina is mechanically detached and rotated around the optic nerve. After rotation, the eye is filled with silicone oil and laser burns are made in the periphery to aid in re-attachment. Approximately 3 days after surgery, the CNV is identified with fluorescein angiography and treated with argon laser photocoagulation.

Theoretically, this appears to be a very elegant way of treating subfoveal CNV. However, complications of the surgery include cyclodiplopia due to the rotation of the retina, so patients must undergo subsequent muscle surgery to correct this condition.

Modalities for treating an occult CNV are limited. Photodynamic therapy, intravitreal triamcinolone (Kenalog), and transpupillary thermotherapy are currently the treatments of choice.

In addition to treatment of predominantly classic subfoveal CNV, verteporfin therapy was superior to a placebo in patients with certain types of subfoveal occult with no classic CNV (17). Verteporfin therapy was superior to a placebo at 24 months following treatment but not at the 12-month examination. Change in mean contrast sensitivity from baseline also favored patients treated with verteporfin therapy at 24 months.

Transpupillary thermotherapy (TTT) uses a long-pulse 810-nanometer infrared laser that penetrates beneath the level of the retinal pigment epithelium. This is a broad beam laser that can be used to treat a large, ill-defined CNV.

Because the laser energy is dissipated below the retinal pigment epithelium, the neurosensory retina is spared (18). The laser light is also poorly absorbed by hemoglobin, which allows treatment through preretinal or subretinal hemorrhages.

TTT clinical trials (19) showed that approximately 8 to 20% of treated patients had some recovery in acuity, 70% remained stable with control of the underlying CNV, and 10-12% continued to have declining acuity. In these latter patients, the decline was not considered to be a result of treatment but rather a result of disease progression. These results are far better than the natural course of occult CNV in which only about 38% of eyes remain stable.

One contraindication to TTT is a history of glaucoma. Up to 50% of patients with glaucoma who were treated with TTT reported a loss of acuity following treatment. The underlying mechanism for this vision loss is unknown.

Drug Treatments for Wet ARMD

A number of clinical trials investigating new treatments for wet ARMD have been conducted, including those using intravitreal anti-VEGF compounds, intravitreal triamcinolone, and posterior sub-Tenon’s injections of anecortave acetate.

Anti-VEGF Treatment

Vascular Endothelial Growth Factor (VEGF) is one of several factors involved in abnormal angiogenesis, i.e., the development of abnormal blood vessels. In patients with CNV, high levels of VEGF have been found within the vitreous cavity.

Anti-VEGF treatment consists of injecting into the vitreous cavity pieces of immunoglobulins (aptamers) that bind to the VEGF. This inhibits its binding to blood vessel endothelial cells and stimulating new growth. Macugen (Eyetech Pharmaceuticals) and Rhu Fab (Genentech) are two anti-VEGF compounds developed for the treatment of CNV.

When injected into the vitreous cavity, anti-VEGF compounds limit angiogenesis in patients with ARMD (20). Clinical trials show that 87.5% of patients who received a series of intravitreal injections with anti-VEGF alone showed stabilization over three months, and 25% of these patients showed an improvement in visual acuity of greater than three lines (21). These results are promising and show suppression of CNV and stabilization to a degree similar to that provided by PDT. There have been no immunologic consequences associated with the use of anti-VEGF because the aptamer is a small molecule.

Intravitreal Triamcinolone

Intravitreal steroid injections using triamcinolone (Kenalog) suppresses the release of VEGF, lessens the inflammatory response caused by CNV, and limits formation of disciform scarring (22).

Preventing formation of disciform scarring is important because this marks the end stage of wet ARMD – the point at which there are currently no available treatment options.

A randomized, open-label control clinical trial is underway to assess the efficacy of treating "ill-defined" or minimally classic CNV with corticosteroid treatment (23). This type of CNV is not well defined with fluorescein angiography and currently not amenable to laser photocoagulation or Photodynamic Therapy.

Anecortave Acetate

Anecortave acetate is an angiostatic compound that has undergone clinical trials to evaluate its ability to suppress CNV. The drug was delivered to the back of the eye through a posterior sub-Tenon's injection and allowed to diffuse across the choroid into the macula. Patients receiving anecortave acetate as a single 15 mg injection experienced 25% less loss in acuity than a placebo group (24).

An additional 18% of patients receiving this drug had an improvement in visual acuity as compared to 0% in the placebo group. Combined with PDT, 78% of patients had no significant increase in vision loss compared to 67% of patients treated with PDT alone. This preliminary data suggest the potential for anecortave acetate to provide retinal specialists with an alternative therapy that will stabilize or improve vision for patients with wet ARMD.

ARMD is a devastating disease that robs elderly patients of their vision and severely impacts their quality of life. The cause of ARMD remains unknown, but, like many diseases, it probably involves a genetic predisposition coupled with exposure to environmental triggers. Avoiding smoking, blue light, hypertension, and other triggers could be helpful in the prevention or management of dry ARMD, as could maintaining high levels of antioxidants in the body.

If ARMD does occur, the next line of defense involves attempting to slow the rate of progression and vision loss. It is commonly accepted that the dry form of the disease precedes the wet form, but it remains possible that these two conditions really represent somewhat different disease processes. Those who accept the dry to wet progression theory believe that it is important to hold the disease at the dry stage as long as possible. Typically this involves a recommendation for sunglasses and antioxidant supplements.

When the wet form occurs, treatment approaches become much more heroic because the end point of the disease is functional blindness. It is hard to imagine a more heroic treatment than detaching the retina, relocating the foveal region, using a laser to destroy the CNV, and then performing muscle surgery to realign the fovea.

Other treatment approaches, e.g., PDT, utilize advanced technologies, but some must be repeated on a frequent basis to hold the ARMD in check.

It is possible that one of the drug therapies, such as anti-VEGF or anecortave acetate, will eventually emerge as the treatment of choice for wet ARMD, but it is more likely that the ideal therapy for this condition has yet to be found.

1. Alexander, Larry J. Primary Care of the Posterior Segment 2nd Ed. Appleton & Lange. 1994.

2. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration: A case-control study in the age-related eye disease study: AREDS report #3. Ophthalmology 107(12): 2224-32. 2000.

3. Delcourt, C. Diaz, J-L. Ponton-Sanchez, et al. Smoking and Age-related Macular Degeneration. Archives of Ophthalmology 116: 1031-5. 1998.

4. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins c and e, beta-carotene, and zinc for age-related macular degeneration and vision loss. Archives of Ophthalmology 119:1417-36. 2001.

5. Richer SP, Stiles W, Statkute L, et al. The Lutein Antioxidant Supplementation Trial. ARVO Abstracts #2542. 2002.

6. Barlett H, Eperjest F. A randomized controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology. Nutrition Journal 2(1)12. 2003.

7. Choroidal Neovascularization Prevention Trial Jresearch Group. Laser treatment in eyes with large drusen. Ophthalmology 42:1646-52. 1998.

8. Kaiser, R.S. Berger, J.W. et al. Laser Burn Intensity and the Risk for Choroidal Neovascularizaton in the CNVPT Fellow Eye Study. Archives of Ophthalmology 119:826-32. 2001.

9. Owens SL, Bunce C, Brannon AJ, et al. Prophylactic laser treatment appears to promote choroidal neovascularization in high-risk ARM: results of an interim analysis. Eye 17(5):623-7. 2001.

10. Complications of Age-related Macular Degeneration Prevention Trial (CAPT). http://www.clinicaltrials.gov.

11. Interim Results of Rheophoresis Study: Macular Degeneration support. (cited 1-13-03)

13. Nanjiani, Max. Fluorescein Angiography, Technique, Interpretation, and Application. Oxford Medical Publications. 1991.

14. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials Archives of Ophthalmology 109:1109-1114. 1991.

15. Treatment of age-related macular degeneration with photodynamic therapy (TAP) study photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: One-year results of 2 randomized clinical trials – TAP report 1. Archives of Ophthalmology 117:1329-1345. 1999.

16. Lai, J.C. Lapolice, D.J. Stinnett, S.S. Visual outcomes following macular translocation With 360 Peripheral Retinectomy. Archives of Ophthalmology 120:1317-1324. 2002

17. Verteporfin in Photodynamic Therapy Study Group. Verteprofin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: Two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization – Verteprofin in Photodynamic Therapy Report No. 2. American Journal of Ophthalmology 131:541-60. 2001.

18. Robertson, D.M. Salomao, D.R. Minn R. The effect of transpupillary thermotherapy on the human macula. Archives of Ophthalmology 120:648-652. 2002.

19. Thach, A.B. Sipperley, J.O. Dugal, P.U. et al. Large-spot size transpupillary thermotherapy for the treatment of occult choroidal neovascularization associated with age-related macular degeneration. Archives of Ophthalmology 121:817-820. 2003.

20. Krzystolik, M.G. Afshari, M.A. Adamis, A.P. et al. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Archives of Ophthalmology 120:338-346. 2002.

21. The Eyetech Study Group. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology 110:979-986. 2003.

22. Gillies, M.C. Simpson, J.M. Luo, W. et al. A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration: one-year results. Archives of Ophthalmology 121:667-673. 2003.

23. Phase I Study of Corticosteroid Treatment of Ill-defined Choroidal Neovascularization in Age-realated Macular Degeneration. http://www.clinicaltrials.gov.

24. Alcon Releases Results for Anecortave Acetate Therapy for Wet Age-Related Macular Degeneration. Press Release, Fort Worth Texas. May 6, 2002. http://www.pslgroup.com.

Pacific University College of Optometry provides On-Line CE as a service to optometrists. The college does not endorse or recommend any products, equipment, or services that might be discussed in the courses. Courses are prepared by individuals believed to be experts in their areas of specialization who are compensated for their efforts. The College relies on their expertise to produce accurate and timely courses. Questions or concerns about courses should be directed to the individual authors and/or the Continuing Education Department at the College of Optometry at kundart@pacificu.edu .

Age-Related Macular Degeneration: Treatment Advances