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September 2014, Issue 73

Laser Photocoagulation:
Is There Still a Use for This Treatment Modality in Exudative AMD?

Michael W. Stewart, MD
Associate Professor of Ophthalmology
Chairman, Department of Ophthalmology
Mayo Clinic Florida

Drugs that neutralize soluble isoforms of vascular endothelial growth factor (VEGF)-A decrease macular thickness and improve visual acuity (VA) in many patients with exudative age-related macular degeneration (AMD).1-3 As a result, intravitreal pharmacotherapy has replaced both photodynamic therapy (PDT) and laser photocoagulation as the preferred treatment option for most patients with choroidal neovascular membranes (CNVM) due to AMD. Photodynamic therapy combined with anti-VEGF pharmacotherapy remains useful for eyes with polypoidal choroidopathy4 or those unresponsive to anti-VEGF monotherapy5 but the indications for laser photocoagulation are no longer well established.

The Macular Photocoagulation Study trials demonstrated the superiority of laser photocoagulation over observation for extrafoveal,6 juxtafoveal,7 and some subfoveal CNVM.8 Laser photocoagulation of extrafoveal CNVM decreases the risk of severe vision loss (>30 letters) compared to observation (25% vs. 60%)6 but this compares poorly to the 5% incidence of moderate (>15 letters) vision loss associated with intravitreal aflibercept or ranibizumab.3 A post hoc analysis of the Macular Photocoagulation Study showed that laser is a more effective treatment option for classic than occult CNVM.9 Unfortunately, even uncomplicated laser photocoagulation of CNVM is plagued by 50% recurrence rates, extension of the treatment scars, and profound post-treatment scotomas.

In the phase III registration trials, ranibizumab and aflibercept were administered to eyes with subfoveal and juxtafoveal – but not extrafoveal – CNVM.3,10,11 In clinical practice, however, surgeons treat most extrafoveal CNVM with anti-VEGF injections instead of laser photocoagulation. Laser has not been compared directly with anti-VEGF injections for extrafoveal CNVM, but a retrospective analysis of non-contemporaneous groups determined that patients who received ranibizumab experienced improved visual acuity (0.46 logMAR to 0.16 logMAR) whereas those treated with laser lost vision (0.52 logMAR to 0.92 logMAR).12 Patients treated with laser (pre-2005) were unable to receive anti-VEGF salvage therapy so these results may not be applicable in the anti-VEGF era. Nonetheless, laser remains a reasonable alternative when recurrent neovascularization is unlikely to involve the fovea and anti-VEGF therapy can be initiated when needed. To minimize the adverse visual effects of a post-treatment scotoma, surgeons may choose to limit the use of laser to predominantly classic, inferior and temporal CNVM that are at least 1000 µm from the foveal center. Laser may also be considered for extrafoveal recurrences in eyes that already have subretinal fibrosis.

Historically, juxtapapillary CNVM has been treated with laser to prevent foveal involvement by growth, exudation and hemorrhage. Accurately defining the extent of the CNVM with indocyanine green angiography, as opposed to fluorescein angiography, facilitates better laser coverage of the lesion.13 To minimize thermal injury to the disc and nerve fiber layer, the Macular Photocoagulation Study recommends that CNVM greater than 4.5 clock hours in size and CNVM with adjacent hemorrhage not be treated.14 Treatment of eligible lesions before visual acuity becomes affected is usually associated with an improved prognosis15 as up to 25% of untreated CNVM result in visual acuities of 20/500 or worse at 3 years.16

Widespread use of laser for juxtapapillary CNVM, however, has been limited by guarded visual acuities13 and high recurrence rates.17 Fortunately, post-laser recurrences may be distant from the fovea, thereby allowing the surgeon to choose among repeat photocoagulation, PDT, and anti-VEGF therapy as second line therapy. Laser-induced scotomas resemble enlarged blind spots, though inadvertent damage to the nerve fiber layer may lead to cecocentral scotomas. Some surgeons believe that longer wavelengths decrease light absorption by retinal chromophores and melanin, increase transmission to the choroid, and limit inner retinal damage, but shorter wavelengths may decrease the incidence of recurrence.

Polypoidal choroidal vasculopathy may be treated successfully with anti-VEGF monotherapy but combination therapy with PDT has been reported to be more effective.4 For eyes with a small number of extrafoveal polyps and vessels, focal laser photocoagulation of the entire lesion may be considered.18

Laser photocoagulation of CNVM has been largely replaced by pharmacotherapy but its judicious use in carefully selected patients with AMD may reduce both cost and treatment burden.

References
1. Martin DF, Maguire MG, Ying G-S. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897-1908.
2. Busbee BG, Ho AC, Brown DM, et al. HARBOR Study Group. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120(5):1046-1056.
3. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548.
4. Koh A, Lee WK, Chen LJ, et al. EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vaculopathy. Retina. 2012;32(8):1453-1464.
5. Tozer K, Roller AB, Chong LP, et al. Combination therapy for neovascular age-related macular degeneration refractory to anti-vascular endothelial growth factor agents. Ophthalmology. 2013;120(10):2029-2034.
6. Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol. 1982;100(6):912-918.
7. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. 1994;112(4):500-509.
8. Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. 1993;111(9):1200-1209.
9. Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Macular Photocoagulation Study Group. Arch Ophthalmol. 1996;114(4):400-412.
10. Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Eng J Med. 2006;355(14):1419-1431.
11. Brown DM, Kaiser PK, Michaels M, et al; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Eng J Med. 2006;355(14):1432-1444
12. Ladas ID, Chatziralli IP, Kotsolis AI, et al. Intravitreal ranibizumab versus thermal laser photocoagulation in the treatment of extrafoveal classic choroidal neovascularization secondary to age-related macular degeneration. Ophthalmologica. 2012;228(2):93-101.
13. Wolf S, Wald KJ, Remky A, Arend O, Reim M. Evolving peripapillary choroidal neovascular membrane demonstrated by indocyanine green choroidal angiography. Retina. 1994;14(5):465-467.
14. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: five year results from randomized clinical trials. Arch Ophthalmol. 1991;109:1109-1111.
15. Ruben S, Palmer H, Marsh RJ. The visual outcome of peripapillary choroidal neovascular membranes. Acta Ophthalmologica. 1994;72:118-121.
16. Aisenbrey S, Gelisken F, Szurman P. Surgical treatment of peripapillary choroidal neovascularization. Br J Ophthalmol. 2007;91:1027-1030.
17. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: five year results from randomized clinical trials. Arch Ophthalmol. 1991;109:1109-1111.
18. Kies JC, Bird AC. Juxtapapillary choroidal neovascularization in older patients. Am J Ophthalmol. 1988;105:11-19.
19. Yuzawa M, Mori R, Haruyama M. A study of laser photocoagulation for polypoidal choroidal vasculopathy. Jpn J Ophthalmol. 2003;47:379-384.

sponsor

Ingrid U. Scott, MD, MPH,  Editor

Professor of Ophthalmology and
Public Health Sciences,
Penn State College of Medicine

 

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