Medical Policy

This document addresses photocoagulation laser treatment of macular drusen. Photocoagulation laser treatment is a technique used to treat soft macular drusen, pale whitish-yellow deposits of extracellular material on the retinal pigment epithelium layer of the retina. Soft drusen accompany the early stages of age-related maculopathy (ARM). The presence of soft macular drusen has been linked to higher rates of progression to age-related macular degeneration (AMD), the advanced stage of ARM.

Investigational and Not Medically Necessary:

Photocoagulation of macular drusen is considered investigational and not medically necessary.

In 2015, Virgili and colleagues published a Cochrane review that included 11 RCTs with a total of 2159 individuals comparing laser treatment to no treatment or a sham intervention. In a meta-analysis of the 11 trials, compared with control interventions, photocoagulation did not significantly reduce the risk of developing choroidal neovascularization (CNV) 2 years after treatment (odds ratio [OR], 1.07, 95% confidence interval [CI]; 0.79 to 1.46). Meta-analyses of secondary outcomes found that photocoagulation did not significantly decrease visual loss of 2 or more lines (9 studies, OR, 0.99, 95% CI; 0.81 to 1.22) or increase the likelihood of drusen reduction (3 studies, OR, 9.16, 95% CI; 6.28 to 13.37). A meta-analysis of 2 trials found a statistically significant reduction in the development of geographic atrophy with laser treatment versus control, but the confidence interval in this analysis was wide (OR, 1.30, 95% CI; 0.38 to 4.51). The authors concluded that laser coagulation is not associated with improved outcomes and noted that the identified trials had a low risk of bias. Limitations noted in the Cochrane review included non-reporting of secondary outcomes (some studies) and not all used a paired study design (both eyes of a participant included), which created difficulties with the data analysis.

The Choroidal Neovascular Prevention Trial (CNVPT)/ Complications of AMD Prevention Trial (CAPT) is one of the key trials evaluating photocoagulation for drusen. In the initial study (the CNVPT), 351 eyes with unilateral or bilateral drusen were randomized to receive green argon laser therapy or observation (Ho, 1999). No statistically significant difference in visual acuity was seen at 4 years of follow-up in 120 subjects randomized to either photocoagulation or observation. A later analysis suggested an increased incidence of CNV development in the laser-treated eyes in subjects with CNV in the fellow eye (CNVPT Research Group, 1998, 2003). Subsequently these subjects were excluded from the trial. The trial continued, was renamed the Complications of AMD Prevention Trial (CAPT), and enrolled only those with bilateral drusen; one eye was assigned to laser treatment and the other received no treatment (CAPT Group, 2006).

The CAPT was conducted at 22 clinical centers involving 1052 participants who were observed for at least 5 years after laser treatment. Follow-up was excellent; less than 3% of visual acuity examinations were missed. At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had visual acuity scores ≥ 3 lines worse than at the initial visit (p=1.00). The cumulative 5-year incidence rates for treated and observed eyes for CNV were 13.3% and 13.3% (p=0.95), respectively; and for geographic atrophy were 7.4% and 7.8% (p=0.64), respectively. The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed eyes (p=0.40). The critical print size doubled in 29.6% of treated eyes and in 28.4% of observed eyes (p=0.70). A total of 7 (0.7%) treated eyes and 14 (1.3%) observed eyes had an adverse event of a ≥ 6-line loss in visual acuity in the absence of late AMD or cataract. As applied in CAPT, low intensity laser treatment did not demonstrate a clinically significant benefit in vision in eyes of people with bilateral large drusen.

An RCT by Owens and colleagues (2006), the Drusen Laser Study (DLS), evaluated laser therapy to prevent CNV and vision loss in high risk ARM (n=156). Two cohorts of subjects, a unilateral group with CNV in the fellow eye and drusen in the study eye, and a bilateral group with bilateral drusen, were randomized to laser-treated or observed groups. The authors noted earlier onset of choroidal neovascularization in the group treated with laser photocoagulation of macular drusen than in the non-treated group. Visual acuity loss also occurred more frequently in the treatment group. Study recruitment was terminated due to the findings.

Friberg and colleagues (2009) reported on the Prophylactic Treatment of Age-related Macular Degeneration (PTAMD) study which enrolled 639 participants (1278 eyes) who were 50 years of age or older with a minimum of five drusen 63 microns or more in diameter in each eye. Eyes were treated with placement of an annular grid of 48 extrafoveal, subthreshold 810-nm diode laser applications centered at, but sparing, the foveola in one eye of each participant, with the control being the other eye. Change in best-corrected visual acuity and development of CNV were compared between untreated and treated eyes. Subthreshold laser treatment did not decrease the incidence of choroidal neovascularization in untreated versus treated eyes. There was a modest visual acuity benefit in treated eyes at 24 months (1.5 letter difference; p=0.04) and in the treated eyes with a baseline visual acuity between 20/32 and 20/63 (4.0 letter difference; p=0.0034); however, this treatment effect was not sustained at 3 years post treatment. The authors noted:

Considering both the PTAMD study and the CAPT findings, laser treatment in its current form is an ineffective method of CNV prophylaxis and we discourage the use of current laser treatment protocols for most patients with bilateral high risk drusen.

In summary, RCTs and the Virgili Cochrane review of 11 RCTs have failed to show a clinical benefit from prophylactic laser treatment of macular drusen. Additionally, some study results suggest laser treatment may accelerate the onset of CNV.

Description of the Disease

Age related macular degeneration is the leading cause of irreversible blindness in people over 50 years of age in the developed world. AMD is a painless, insidious process. In its earliest stages, it is characterized by minimal visual impairment and the presence of drusen, subretinal accumulations of cellular debris adjacent to the basement membrane of the retinal pigment epithelium. Drusen are characterized as being either hard or soft. Soft drusen are at greater risk for developing wet AMD.

Large drusen appear as pale yellow or pale gray domed elevations and result in thickening of the space between the retinal pigment epithelium and its blood supply, the choriocapillaries. Clinical and epidemiologic studies have shown that the presence of large or numerous soft drusen increase the risk of the development of CNV in eyes with AMD. For example, in individuals with bilateral drusen, the 3-year risk of developing CNV is estimated to be 13%, rising to 18% for those over the age of 65. The emergence of CNV greatly increases the risk of subsequent irreversible loss of vision.

Description of the Technology

Two different kinds of low energy laser therapies, argon and infrared laser, have been investigated as techniques to eliminate drusen by photocoagulation in an effort to prevent the evolution to CNV, ultimately leading to improved preservation of vision. The lasers used are those that are widely used for standard photocoagulation of extrafoveal choroidal neovascularization. Therefore, the treatment of macular drusen represents an additional indication for an existing U.S. Food and Drug Administration (FDA) approved laser.

During photocoagulation laser surgery of macular drusen, laser light rays are directed into the eye, focusing on abnormal blood vessels that are growing beneath the retina. The laser seals the blood vessels from further leakage in the hope of preventing further vision loss. Prior to the treatment, eye drops are given to dilate the pupil and numb the eye. The individual remains awake but may experience mild pain, which can usually be relieved with non-prescription pain medication. The laser treatment usually takes less than thirty minutes to complete, and the individual typically can go home immediately following surgery.

Age-Related Macular Degeneration (AMD): A disease blurring the sharp, central vision needed for "straight-ahead" activities such as reading, sewing, and driving. AMD affects the macula, the part of the eye used for fine detail and causes no pain. In some cases, AMD advances so slowly that people notice little change in their vision and in others, the disease progresses faster and may lead to a loss of vision in both eyes. AMD occurs in wet and dry form.

Choroidal Neovascularization: A condition characterized by the development of new blood vessels across the back portion of the eye, which may interfere with vision.

Dry AMD: Occurs when light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye. It generally affects both eyes, but vision can be lost in one eye while the other eye seems unaffected. Dry AMD has three stages, all of which may occur in one or both eyes:

1. Early AMD: People with early AMD have either several small drusen or a few medium-sized drusen. At this stage, there are no symptoms and no visual loss.
2. Intermediate AMD: People with intermediate AMD have either many medium-sized drusen or one or more large drusen. Some people see a blurred spot in the center of their vision and more light may be needed for reading and other tasks.
3. Advanced Dry AMD: In addition to drusen, people with advanced dry AMD have a breakdown of light-sensitive cells and supporting tissue in the central retinal area. This breakdown can cause a blurred spot in the center of the individual’s vision. Over time, the blurred spot may enlarge and darken taking more of central vision and the individual may have difficulty reading or recognizing faces until they are very close to the other person.

Foveola: Is located within a region called the macula, a yellowish, cone photo receptor filled portion of the human retina. The foveola is approximately 0.35 mm in diameter and lies in the center of the fovea and contains only cone cells. In this region the cone receptors are found to be longer, slimmer and more densely packed than anywhere else in the retina, thus allowing that region to have the potential to have the highest visual acuity in the eye.

Wet AMD: Occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels tend to be very fragile and often leak blood and fluid. The blood and fluid raise the macula from its normal place at the back of the eye and damage to the macula occurs rapidly; loss of central vision can occur quickly. Wet AMD is considered to be advanced AMD and is more severe than the dry form.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services are also Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Complications of Age-Related Macular Degeneration Prevention Trial Research Group. Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial. Ophthalmology. 2006; 113(11):1974-1986.
2. Figueroa M, Schocket LS, Dupont J, et al. Long-term effect of laser treatment for dry age-related macular degeneration on choroidal hemodynamics. Am J Ophthalmol. 2006; 141(5):863-867.
3. Friberg TR, Brennen PM, Freeman WR, Musch DC.; PTAMD Study Group. Prophylactic treatment of age-related macular degeneration report number 2: 810-nanometer laser to eyes with drusen: bilaterally eligible patients. Ophthalmic Surg Lasers Imaging. 2009; 40(6):530-538.
4. Friberg TR, Musch DC, Lim JI, et al.; PTAMD Study Group. Prophylactic treatment of age-related macular degeneration report number 1: 810-nanometer laser to eyes with drusen. Unilaterally eligible patients. Ophthalmology. 2006; 113(4):612-622.
5. Ho AC, Maguire MG, Yoken J et al. Laser-induced drusen reduction improves visual function at 1 year. Choroidal Neovascularization Prevention Trial Research Group. Ophthalmology. 1999; 106(7):1367-1373.
6. Owens SL, Bunce C, Brannon AJ, et al.; Drusen Laser Study Group. Prophylactic laser treatment hastens choroidal neovascularization in unilateral age-related maculopathy: final results of the drusen laser study. Am J Ophthalmol. 2006; 141(2):276-281.
7. The Choroidal Neovascularization Prevention Trial Research Group. Choroid neovascularization in the Choroidal Neovascular Prevention Trial. Ophthalmology. 1998; 105(8):1364-1372.
8. The Choroidal Neovascularization Prevention Trial Research Group. Laser treatment in fellow eyes with large drusen: updated findings from a pilot randomized clinical trial. Ophthalmology. 2003; 110(5):971-978.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Retina Vitreous Panel, Preferred Practice Patterns Committee. American Academy of Ophthalmology (AAO). Age-related macular degeneration. For additional information visit the AAO website: http://aao.org. Accessed on January 16, 2022.
2. Virgili G, Michelessi M, Parodi MB, et al. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration. Cochrane Database Syst Rev. 2015;(10):CD006537.

1. National Eye Institute. U.S. National Institutes of Health. Age-Related Macular Degeneration. Updated June 2021. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration. Accessed on January 10, 2023.

Age Related Macular Degeneration
Laser Therapy, Eye
Macular Drusen, Photocoagulation
Photocoagulation of Macular Drusen