It's an exciting time in the development of new treatments for age-related macular degeneration (AMD). However, even as new therapies gain regulatory approval, the laser will remain a mainstay in treating choroidal neovascularization (CNV) resulting from AMD, which causes 90% of severe vision loss.

Over the past two decades, the Macular Photocoagulation Study (MPS) has demonstrated that laser photocoagulation of CNV located in subfoveal, juxtafoveal and extrafoveal locations effectively limits severe visual acuity loss compared with the natural course of untreated CNV.

Furthermore, technological advances have produced a variety of lasers, which offer a spectrum of wavelengths for photocoagulation. In this article, I'll review some of the latest research in this area and other points to consider as you make your treatment choices.

Visible-light wavelengths

For the past 10 years, researchers have been exploring the advantages and disadvantages of visible-light laser wavelengths (488 to 630 nm) for treating CNV. A review of the literature suggests that your choice of laser wavelength for traditional laser photocoagulation will make little difference in the treatment outcome. Ultimately, your success will depend more on the adequacy of the laser burn and complete laser coverage of the CNV. (Keep in mind that the burn should be adequately white and cover all borders of the CNV.) However, because research continues in this area, it's important for you to understand the capabilities of these lasers and how they work.

Three pigments in the posterior segment absorb laser energy: melanin, xanthophyll and hemoglobin. Melanin most effectively absorbs all laser wavelengths. Xanthophyll, located in the inner macular retina, absorbs blue light well, green light poorly and yellow and red light minimally. Because xanthophyll is present in the inner and outer plexiform layers, it is theorized that blue-green light could damage the inner retina, whereas laser light of a longer wavelength may spare these layers, moving deeper into the retina into the level of the choroid. Hemoglobin absorbs blue, green and yellow light well and red light poorly.

Despite the varying degrees of absorption of these pigments, the retinal pigment epithelium (RPE) and choroid are the primary sites of absorption of laser energy because melanin most effectively absorbs energy. Additionally, because the heat is so intense during photocoagulation, it may be transferred from the RPE to more superficial retinal layers.

In a prospective, randomized clinical trial of photocoagulation of new or recurrent subfoveal CNV (SFCNV) lesions in AMD, patients were randomly assigned to receive either krypton red or argon green laser treatment. In the new subfoveal neovascularization trial, there was no difference in the average loss of visual acuity, contrast threshold or reading speed from baseline between eyes treated with green or red laser.

In the recurrent subfoveal neovascularization trial, no significant difference was found in the average loss of visual acuity after treatment among eyes in the two laser wavelength groups. And even though eyes treated with red laser read 16 words per minute slower than those treated with green laser and required 1.4 times more contrast to identify letters compared with eyes treated with the green laser, the differences aren't clinically relevant. Overall, there appears to be no practical advantage of one wavelength (red or green) over the other in the treatment of CNV secondary to AMD.

Preference shift

The green laser wavelength has largely supplanted the blue-green laser in common clinical usage. You might find the blue-green laser harder to focus because it's scattered by the ocular media. Furthermore, you would need higher energy levels because scatter attenuates the blue light, and blue light is absorbed by the cornea and lens. Yellow laser and diode laser haven't been studied in a randomized, prospective clinical trial.

Longer wavelengths

Longer wavelengths present their own advantages and disadvantages. The comparatively longer wavelengths of near-infrared diode lasers (780 to 840 nm) scatter less as they traverse ocular media, such as cataract and vitreous hemorrhage. And because these wavelengths are invisible, photophobic patients may prefer diode lasers.

However, the ocular pigment doesn't absorb infrared light as effectively as visible light. Therefore, you'll need to increase the exposure, or intensity, of the diode laser to create a lesion clinically equivalent to that achieved with an argon green laser. As a result, your patients may be more uncomfortable during diode laser treatment than they would be during argon photocoagulation.

Clinical trials have found that a micropulsed and continuous-wave 810-nm diode laser effectively treated CNV resulting from AMD. Within 6 months after treatment, CNV recurred or persisted in 30% of cases, which is roughly comparable to the MPS rate.

To achieve deep confluent treatment over the CNV, the laser power was set at levels higher than those ordinarily used with an argon-green laser. In addition, the lesions treated by the diode laser seemed to be deeper and appeared as well demarcated, completely black areas of choriocapillaris atrophy on fluorescein angiography.

In general, the authors believed the diode laser was more difficult to use than an argon or krypton laser and had a comparatively narrow therapeutic power range. To date, there have been no reports from prospectively randomized trials comparing the diode laser with an argon green, krypton red or dye laser in the treatment of CNV.

New laser applications

The latest innovations in treatments of neovascular AMD are photodynamic therapy (PDT) and transpupillary thermotherapy (TTT).

The FDA recently approved PDT with verteporfin to treat predominantly classic SFCNV lesions. The treatment uses a 689-nm diode laser to activate verteporfin -- a photosensitive intravenous drug that is absorbed by the damaged blood vessels. Activation of verteporfin induces vascular thrombosis and subsequent closure of the CNV.

The Treatment of Age-Related Macular Degeneration with PDT (TAP) Study Group showed that verteporfin was more effective than placebo for treating predominantly classic SFCNV at 1 and 2 years of follow-up. However, verteporfin had little or no benefit in predominantly occult SFCNV lesions 1 year after treatment.

Although PDT shows promise for patients with predominantly classic SFCNV, it will be useful in only 20% of all CNV cases according to approved indications. Consequently, traditional laser photocoagulation will continue to figure significantly into our treatment of CNV caused by AMD.

In TTT, a modified diode laser delivers heat to the choroid and RPE through the pupil. Results from a pilot study investigating the efficacy of TTT in occult SFCNV in patients with AMD suggested that vision improved or stabilized in 75% of treated patients. A randomized, prospective clinical trial will further evaluate this treatment.

Future of lasers

Lasers continue to play a major role in treating CNV in patients with AMD. As new treatment modalities are developed, laser technology will be adapted to fill new roles. However, traditional laser photocoagulation will remain a valuable tool in your treatment of extrafoveal and juxtafoveal CNV in patients with AMD.

For More Information

Bressler S. Does Wavelength Matter When Photocoagulating Eyes with Macular Degeneration or Diabetic Retinopathy. Arch Ophthalmol 1993;111:177-180.

Dyer DS, Bressler SB, Bressler NM. The Role of Laser Wave-length in the Treatment of Vitreoretinal Diseases. Current Opinion in Ophthalmology 1994;111:35-43.

Friberg TR, Karataza EC. The Treatment of Macular Disease Using a Micropulsed and Continuous Wave 810-nm Diode Laser. Ophthalmology 1997;104:2030-2038.

Macular Photocoagulation Study (MPS) Group. Evaluation of Argon Green vs Krypton Red Laser for Photocoagulation of Subfoveal Choroidal Neovascularization in the Macular Photocoagulation Study. Arch Ophthalmol 1994;112:1176-1184.

Reichel E, Berrocal AM, Ip M, et al. Transpupillary Thermother-apy of Occult Subfoveal Choroidal Neovascularization in Patient with Age-related Macular Degeneration. Ophthalmology 1999;106:1908-1914.

Michael J. Cooney, M.D., is a vitreoretinal fellow at the Wilmer Ophthalmological Institute and will join the faculty as an assistant professor of ophthalmology at Johns Hopkins in July. His clinical practice focuses on medical retina and vitreous diseases, and his research interests include angiogenesis, drug delivery, clinical trials and the clinical development of new technology.