Surgery Section - Photocoagulation of Macular Drusen

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Age-related macular degeneration (AMD) is a painless, insidious process. In its earliest stages, it is characterized by minimal visual impairment and the presence of large or "soft" drusen, i.e., subretinal accumulations of cellular debris adjacent to the basement membrane of the retinal pigment epithelium.

Large drusen appear as large pale yellow or pale gray domed elevations and result in thickening of the space between the retinal pigment epithelium and its blood supply, the choriocapillaris. Clinical and epidemiologic studies have shown that the presence of large and/or numerous soft drusen increases the risk of the development of choroidal neovascularization (CNV) in eyes with AMD. For example, in patients 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.

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.

Policy/Criteria

Destruction of macular drusen with laser therapy is considered investigational.

Scientific Background

A variety of studies have shown that laser therapy can induce regression of drusen, not only at the treatment site, but also at sites remote from the laser. (2-5)  Earlier, smaller studies showed variable results concerning the outcomes of greatest interest, severe vision loss from atrophy and the development of choroidal neovascularization (CNV).  Figueroa and colleagues reported on a group of 46 patients with confluent soft drusen. (6) A total of 30 patients with bilateral drusen were randomized to receive argon green laser therapy in one eye. The remaining 16 patients had choroidal neovascularization in one eye and laser therapy was performed on the other eye. Although laser therapy resulted in resolution of the drusen, after 3 years there was no difference among the groups regarding development of CNV.  Frennesson reported reductions in exudative complications in a pilot study of 13 patients randomized to mild laser treatment of soft drusen maculopathy at 8 years follow-up, yet both the treatment group and control group (n=16) had significant decreases in visual acuity. (7)  Ruiz-Moreno and colleagues reported macular atrophy and a significant decrease in best-corrected visual acuity in 52 eyes that underwent photocoagulation of soft drusen at an average of 50.1 months follow-up. (8)

Recently completed randomized clinical trials do not validate the role of photocoagulation in the treatment of macular degeneration indicating that low intensity laser treatment does not demonstrate a clinically significant benefit for vision and may accelerate the rate of CNV development in treated eyes.

The Choroidal Neovascular Prevention Trial (CNPVT) consisted of a randomized trial of 351 eyes with unilateral or bilateral drusen that were randomized to receive green argon laser therapy or observation. (9) Laser-treated eyes with 50% or more drusen reduction at one year had more increases in visual acuity compared to the control group. However, short-term visual acuity is an intermediate outcome. A subsequent analysis suggested that there was an increased incidence of CNV development in the laser-treated eyes in patients with CNV in the fellow eye and further enrollment of new patients was halted. (10)

Subsequently, the Choroidal Neovascular Prevention Trial continued, renamed as the Complications of AMD Prevention Trial (CAPT), which enrolled only those patients with bilateral drusen; one eye was assigned to laser treatment and the other received no treatment. The recruitment of 1,052 patients at 22 clinical centers across the United States was completed in March 2001.  In 2006, CAPT published five year results which found 20.5% of treated eyes and 20.5 % of observed eyes had worse visual acuity (P= 1.00) and 13.3% of both treated and non-treated eyes developed CNV (P=.95). (11)  The authors concluded that low-intensity laser treatment did not demonstrate a clinically significant benefit for vision in eyes of people with bilateral large drusen.

In 2003, the CNPVT Research Group reported 4-year follow-up data from the Fellow Eye Study (FES), a randomized pilot study involving patients who had exudative AMD in one eye and 10 or more large drusen in the contralateral (fellow) eye. (12) The fellow eye in this study was randomized to either laser treatment or observation. Enrollment in this study was suspended early because there was a higher incidence of CNV within 12 months of study enrollment in laser-treated eyes than in observed eyes. Longer follow-up demonstrated that while laser treatment appeared to accelerate the development of clinically detectable CNV, the cumulative risk was similar in treated and untreated eyes by 30 months or greater. The authors note that a high proportion of enrolled patients did not complete clinic visits beyond 24 months (the original duration of the study). Returning patients in both groups were somewhat younger than those who did not return; therefore, rates of CNV and vision loss may be underestimated. The authors further note that at no time during the study were there significant differences in visual function between the observed and laser treated eyes despite different rates of development of CNV.

Also in 2003, Owens and colleagues reported interim results of a randomized, multicenter clinical trial in which patients with age-related maculopathy were randomized to receive prophylactic macular photocoagulation or no treatment. (13) There were 156 patients included in the interim analysis, and timed information was available on 153. CNV occurred in 21 of 81 (26%) patients in the Treatment Group and in 13 of 75 (17%) patients in the No Treatment Group (P=0.19). Kaplan-Meier survival analysis showed earlier onset of CNV in the Treatment Group compared to patients in the No Treatment Group (statistical significance not calculated). Visual acuity loss at 2 years occurred in 9 of 54 (17%) patients in the Treatment Group compared to the 2 of 48 (4%) patients in the No Treatment Group (P=0.056). Although these differences were not statistically significant, concern about laser-induced CNV led to early termination of study recruitment.

In 2006, Owens and colleagues published final results of the Drusen Laser Study (DSL) which demonstrated that CNV onset was approximately six months earlier in the laser-treated group compared with the no-laser group (P= .05). (14)  The authors advised against prophylactic laser treatment in age-related maculopathy when a neovascular process has already occurred in one eye.

Olk and colleagues reported results of an initial randomized pilot study of infrared laser therapy; this study enrolled 152 patients (229 eyes) who had either bilateral drusen or unilateral drusen if CNV was detected in the fellow eye. (15) The eyes were randomized to receive infrared laser therapy or observation. While laser therapy was associated with resolution of drusen and improved visual acuity, the study was not powered to detect an effect on progression to choroidal neovascularization.

The Prophylactic Treatment of Age-Related Macular Degeneration trial (PTAMD), was formed based on the results of the initial pilot study above.  It was designed to determine whether infrared laser therapy can decrease or at least delay the development of CNV and the associated severe visual loss. (16)

Results of the PTAMD trial, published in 2006 by Frieberg and colleagues, found the rate of CNV events in treated eyes consistently exceeded that in observed eyes.  The authors concluded that prophylactic laser treatment to an eye with multiple large drusen in a patient whose fellow eye has already suffered a neovascular event places the treated eye at higher risk of developing CNV and they advise against treatment in these eyes.

Additionally, an October 2005 BCBSA TEC Special Report on the treatment of age-related macular degeneration supports the conclusions given above. (17) The TEC Special report noted drusen ablation has a tenable biological basis but consistent evidence for benefit is lacking with a potential for harm.

Given the above results, which indicate a lack of clinically significant benefit for vision and a potential for increased CNV events in treated eyes, photocoagulation of macular drusen for the treatment of macular degeneration does not meet TEC criteria and is considered investigational.

An updated search of the peer-reviewed literature in the MEDLINE database through January 8, 2008 identified no additional published studies that alter the above conclusions.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 9.03.11
2. Figueroa MS, Regueras A, Bertrand J. Laser photocoagulation to treat macular soft drusen in age-related macular degeneration. Retina 1994;14(5):391-96
3. Frennesson IC, Nilsson SEG. Effects of argon (green) laser treatment of soft drusen in early age-related maculopathy: A 6 month prospective study. Br J Ophthalmol 1995;79(10):905-9
4. Frennesson C, Nilsson SEG. Prophylactic laser treatment in early age related maculopathy reduced the incidence of exudative complications. Br J Ophthalmol 1998:82(10):1169-74
5. Rodanant N, Friberg TR, Cheng L, Aurora A, Bartsch D, Toyoguchi M, Corbin PS,El-Bradey MH, Freeman WR. Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration. Am J Ophthalmol 2002 Oct;134(4):577-85
6. Figueroa MS, Regueras A, Bertrand J et al. Laser photocoagulation for macular soft drusen. Updated results. Retina 1997;17(5):378-84
7. Frennesson CI. Prophylactice laser treatment in early age-related maculopathy: an 8-year follow-up in a randomized pilot study shows a reduced incidence of exudative complications. Acta Ophthalmol Scand 2003;81(5):449-54
8. Ruiz-Moreno J, De la Vega C, Zarbin MA. Macular atrophy after photocoagulation of soft drusen. Retina 2003;23(3):315-21
9. 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;106:1367-73
10. The Choroidal Neovascularization Prevention Trial Research Group. Choroid neovasularization in the Choroidal Neovascular Prevention Trial. Ophthalmology 1998;105(8):1364-72
11. The Complications of Age-Related Macular Degeneration Prevention Trial. Laser treatment in patients with bilateral large drusen.  Ophthalmology 2006;113(11):1974-1986. www.nei.nih.gov/neitrials/viewStudyWeb.aspx?id=70  (Verified 2/11/08)
12. 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):971-8
13. Owens SL, Bunce C, Brannon AJ, Wormald R, Bird AC; Drusen Laser Study Group. Prophylactic laser treatment appears to promote choroidal neovascularisation in high-risk ARM: results of an interim analysis. Eye 2003;17(5):623-7
14. 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):276-81
15. Olk RJ, Friberg TR, Stickney KL et al. Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of nonexudative age-related macular degeneration: two-year results of a randomized pilot study. Ophthalmology 1999;106:2082-90
16. Friberg TR, Musch DC, Lim JI et al.  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
17. TEC Special Report: Current and Evolving Strategies in the Treatment of Age-Related Macular Degeneration (HTML): 2006;  BlueCross and BlueShield Association Technology Evaluation Center, Volume 20, No. 11 (Verified 2/11/08)

Cross References

Photodynamic Therapy for Subfoveal Choroidal Neovascularization, TRG Medical Policy Manual, Medicine, Policy No. 87

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