Macular Photocoagulation Study 
(MPS)

Purpose

To evaluate laser treatment of choroidal neovascularization (CNV) through randomized, controlled clinical trials. The Macular Photocoagulation Study (MPS) consisted of three sets of randomized, controlled clinical trials. Change in best-corrected visual acuity from baseline was the primary outcome for all MPS trials. Other measures of vision were evaluated in each set of trials. The purpose of each is described below.

Argon Study: To determine whether argon blue-green laser photocoagulation of leaking abnormal blood vessels in choroidal neovascular membranes outside the fovea (200 to 2,500 microns from the center of the foveal avascular zone [FAZ]) is of benefit in preventing or delaying loss of central vision in patients with age-related (senile) macular degeneration (AMD), presumed ocular histoplasmosis (POH), and idiopathic neovascular membranes (INVM). A separate trial was conducted for each of the three underlying conditions.

Krypton Study: To determine whether krypton red laser photocoagulation of choroidal neovascular lesions with the posterior border 1 to 199 microns from the center of the FAZ is of benefit in preventing or delaying large losses of visual acuity in patients with AMD, POH, and INVM. A separate trial was conducted for each of the three underlying conditions.

Foveal Study: To determine whether laser photocoagulation is of benefit in preventing or delaying further visual acuity loss in patients with new (never treated) or recurrent (previously treated with laser photocoagulation) choroidal neovascularization under the center of the FAZ. Two separate trials, one for each type of lesion, were carried out.
 

Background

Age-related macular degeneration is the leading cause of severe visual acuity loss in the United States among people older than 60. Presumed ocular histoplasmosis is a leading cause of visual loss in young and middle-aged persons living in the region of the United States in which histoplasmosis is endemic ("histo belt"), an area that includes all of Arkansas, Kentucky, Missouri, Tennessee, and West Virginia and major portions of Alabama, Illinois, Indiana, Iowa, Kansas, Louisiana, Maryland, Mississippi, Nebraska, Ohio, Oklahoma, Texas, and Virginia. Both disorders are associated with CNV that damages the macula. Idiopathic CNV leads to acute loss of central vision but is not attributed to any known disease process. In all three disorders, visual loss results from complications of CNV in the macula.
 

Description

In each randomized trial conducted by the MPS Group, focal laser photocoagulation was compared to observation without treatment. Patients were assigned to laser treatment or to observation with equal probability. The first set of MPS randomized trials, the Argon Study, focused on the effectiveness of photocoagulation with argon blue-green laser in eyes with discrete extrafoveal choroidal neovascularization. The study investigators, who began recruiting patients in 1979, estimated that 550 patients with AMD and 750 with POH would be required. Follow-up was to continue for 5 years to determine whether argon laser photocoagulation treatment could prevent or delay visual acuity loss in these patients. 

After the initiation of the Argon Study, a new krypton red laser became available. The new wavelength offered theoretical advantages over the argon laser for treating CNV that extended inside the FAZ of the macula. The Krypton Study design was analogous to the Argon Study, with the investigation of three underlying conditions, except that CNV was closer to the FAZ center.

The third set of MPS clinical trials, the Foveal Study, was designed to determine whether laser photocoagulation was effective for delaying or preventing further visual acuity loss in AMD patients who have subfoveal CNV. Among patients assigned to laser treatment in the Foveal Study, argon laser treatment was compared with krypton red laser treatment of these lesions. The investigators originally projected that about 350 patients would be required for each clinical trial of the Foveal Study.
 

Patient Eligibility

Common Eligibility Criteria for the Argon, Krypton, and Foveal Studies:
To be eligible, men and women must have been experiencing visual symptoms attributable to the macular lesion, such as decreased visual acuity or Amsler grid distortion, at the time of entry into the study. They also must have had visible, well-demarcated hyperfluorescence characteristic of classic choroidal neovascularization on fluorescein angiography. AMD patients were 50 years of age or older and had drusen visible in the macula of at least one eye. POH patients were at least 18 years old and had at least one characteristic histo spot in one or both eyes. INVM patients were at least 18 years old and had no evidence of AMD, POH, angioid streaks, high myopia, diabetic retinopathy, or any other condition that could be the cause of the neovascularization. In particular, INVM patients had neither drusen greater than MPS Standard Photograph No. 1.1 nor histo spots in either eye.

Additional Patient Eligibility Criteria for the Argon Study: 
Each patient had a visible serous detachment of the sensory retina with a diffuse area of leakage, discrete choroidal neovascularization outside the fovea (200-2,500 microns from the center of the FAZ), and visual acuity of 20/100 or better in the study eye.

Additional Patient Eligibility Criteria for the Krypton Study:
All patients had a neovascular lesion consisting of neovascularization and possibly blood and/or pigment that extended into the FAZ. The posterior border of CNV could extend as close as 1 micron to the FAZ center. Visual acuity of the study eye was 20/400 or better.

Additional Patient Eligibility Criteria for the Foveal Study: 
Only patients with AMD were eligible for this study. Fluorescein angiography of the eligible eye had to show evidence of a leaking choroidal neovascular membrane, some part of which extended under the center of the FAZ, or a neovascular lesion consisting of an old laser treatment scar and contiguous leaking neovascularization within 150 microns of the center of the FAZ. New, never-treated subfoveal lesions were less than four disc areas in size. Recurrent lesions were less than six disc areas in size, including the old treatment scar and new neovascularization. Best-corrected visual acuity was no better than 20/40 and no worse than 20/320.
 

Patient Recruitment Status

Recruitment for the MPS trials of laser treatment of extrafoveal neovascular lesions began in February 1979, for juxtafoveal CNV in January 1981, and for subfoveal CNV in February 1986. Recruitment was completed for the Argon Study in 1983, for the Krypton Study in 1987, and for the studies of new and recurrent subfoveal CNV in 1990.
 

Results

Accrual of patients in the Argon Study was halted early in all three trials: in March 1982 for AMD patients and in May 1983 for POH and INVM patients, after 236 patients with AMD, 262 with POH, and 67 with INVM had been enrolled. These decisions were based on findings that argon laser treatment, as applied in the study, dramatically reduced severe visual acuity loss in these conditions. Patients in the Argon Study trials were discharged from the study as they completed 5 years of regular follow-up examinations.

In the Krypton Study, patient accrual was halted for the POH trial in December 1986 because of evidence of treatment benefit in these 287 patients. Enrollment of patients with AMD or INVM was halted in December 1987 after 496 and 49 eyes, respectively, had been enrolled. In 1989, sufficient data had accumulated to demonstrate that there was a beneficial effect of krypton red laser treatment in eyes with AMD. The benefit was most pronounced in normotensive patients and was not apparent among hypertensive patients. Findings for patients with INVM were intermediate between those of patients with AMD and POH. Patients in the Krypton Study were discharged as they completed 5 years of regular followup, except for those enrolled during the last 2 years of patient accrual. All patients had been discharged from the study by March 31, 1991.

In December 1989, patient enrollment was completed in the Foveal Study trial for never-treated subfoveal choroidal neovascularization; 373 patients were randomized. Enrollment of patients with subfoveal recurrence after laser treatment continued until December 1990. Findings of treatment benefit for both groups of eyes were published initially in September 1991. Patients were discharged as they completed 4 years of followup or by December 1993, whichever occurred first.

The Macular Photocoagulation Study publications provide guidelines for the evaluation and management of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration, ocular histoplasmosis, and idiopathic choroidal neovascularization. For patients with any of the three above conditions, eyes with well-demarcated areas of classic choroidal neovascularization, as defined by fluorescein angiography, had a better visual prognosis when treated with laser photocoagulation, performed according to MPS guidelines, than when managed by observation. These outcome data apply to all three conditions when the position of the neovascularization is extrafoveal or juxtafoveal, that is, when the CNV does not involve the center of the fovea.

Eyes with age-related macular degeneration and subfoveal choroidal neovascularization benefited more from laser treatment than from observation when MPS eligibility guidelines and treatment protocol were observed. Overall, eyes receiving direct laser treatment to the fovea for new CNV immediately lost more visual acuity than observed eyes. However, the amount of visual acuity loss in observed eyes increased to the level of loss in treated eyes at 12 months and exceeded the level thereafter. Eyes with smaller lesions and worse initial visual acuity had greater and earlier benefits of laser treatment. Eyes with large subfoveal neovascular lesions and good initial visual acuity are not good candidates for focal laser photocoagulation.
 
 

Publications

  • Macular Photocoagulation Study Group: Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Arch Ophthalmol 115: 741-747, 1997.
  • Macular Photocoagulation Study Group: Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 114: 400-412, 1996.
  • Macular Photocoagulation Study Group: Five-year follow-up of fellow eyes of individuals with ocular histoplasmosis and unilateral extrafoveal or juxtafoveal choroidal neovascularization. Arch Ophthalmol 114: 677-688, 1996.
  • Macular Photocoagulation Study Group: Laser photocoagulation for neovascular lesions nasal to the fovea: Results from clinical trials for lesions secondary to ocular histoplasmosis or idiopathic causes. Arch Ophthalmol 113: 56-61, 1995.
  • Macular Photocoagulation Study Group: The influence of treatment extent on the visual acuity of eyes treated with krypton laser for juxtafoveal choroidal neovascularization. Arch Ophthalmol 113: 190-194, 1995.
  • Macular Photocoagulation Study Group: Visual outcome after laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. The influence of initial lesion size and initial visual acuity. Arch Ophthalmol 112: 480-488, 1994.
  • Macular Photocoagulation Study Group: Persistent and recurrent neovascularization after laser photocoagulation for subfoveal choroidal neovascularization of age-related macular degeneration. Arch Ophthalmol 112: 489-499, 1994.
  • Macular Photocoagulation Study Group: Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Arch Ophthalmol 112: 800-809, 1994.
  • Macular Photocoagulation Study Group: Evaluation of green versus red laser for photocoagulation of subfoveal choroidal neovascularization in the macular photocoagulation study. Arch Ophthalmol 112: 1176-1184, 1994.
  • Birch DG, Anderson JL, Fish GE, Jost BF: Pattern-reversal electroretinographic follow-up of laser photocoagulation for subfoveal neovascular lesions in age-related macular degeneration. Am J Ophthalmol 116: 148-155, 1993.
  • Fine SL: The case for treating subfoveal neovascularization in patients with age-related macular degeneration, Franklin RM (ed): Retina and Vitreous. Proceedings of the Symposium on Retina and Vitreous, New Orleans Academy of Ophthalmology, New York, Kugler Publications 29-30, 1993.
  • Macular Photocoagulation Study Group: Five-year followup of fellow eyes of patients with age-related macular degeneration and unilateral extrafoveal choroidal neovascularization. Arch Ophthalmol 111: 1189-1199, 1993.
  • Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Arch Ophthalmol 111: 1200-1209, 1993.
  • Birch DG, Anderson AL, Fish GE, Jost BF: Pattern-reversal electroretinographic acuity in untreated eyes with subfoveal neovascular membranes. Invest Ophthalmol Vis Sci 33(7): 2097-2104, 1992.
  • Orr PR, Blackhurst DW, Hawkins BS: Patient and clinic factors predictive of missed visits and inactive status in a multicenter clinical trial. Controlled Clin Trials 13: 40-49, 1992.
  • Bressler NM, Bressler SB, Alexander J, Javornik N, Fine SL, Murphy RP, Macular Photocoagulation Study Reading Center: Loculated fluid: A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Arch Ophthalmol 109: 211-215, 1991.
  • Macular Photocoagulation Study Group: Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Arch Ophthalmol 109: 1109-1114, 1991.
  • Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 109: 1219-1230, 1991.
  • Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal recurrent neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 109: 1232-1241, 1991.
  • Macular Photocoagulation Study Group: Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the Macular Photocoagulation Study. Arch Ophthalmol 109: 1242-1257, 1991.
  • Hawkins BS, Prior MJ, Fisher MR, Blackhurst DW: Relationship between rate of patient enrollment and quality of clinical center performance in two multicenter trials in ophthalmology. Controlled Clin Trials 11: 374-394, 1990.
  • Macular Photocoagulation Study Group: Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 108: 816-824, 1990.
  • Macular Photocoagulation Study Group: Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Arch Ophthalmol 108: 825-831, 1990.
  • Macular Photocoagulation Study Group: Krypton laser photocoagulation for idiopathic neovascular lesions. Results of a randomized clinical trial. Arch Ophthalmol 108: 832-837, 1990.
  • Bressler SB, Maguire MG, Bressler NM, Fine SL, Macular Photocoagulation Study Group: Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. Arch Ophthalmol 108: 1442-1447, 1990.
  • Blackhurst DW, Maguire MG, Macular Photocoagulation Study Group: Reproducibility of refraction and visual acuity measurement under a standard protocol. Retina 9(3): 169-169, 1989.
  • Chamberlin JA, Bressler NM, Bressler SB, Elman MJ, Murphy RP, Flood TP, Hawkins BS, Maguire MG, Fine SL, Macular Photocoagulation Study Group: The use of fundus photographs and fluorescein angiograms in the identification and treatment of choroidal neovascularization in the Macular Photocoagulation Study. Ophthalmology 96(10): 1526-1534, 1989.
  • Macular Photocoagulation Study Group: Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Arch Ophthalmol 107: 344-352, 1989.
  • Macular Photocoagulation Study Group: Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis: Results of a randomized clinical trial. Arch Ophthalmol 105: 1499-1507, 1987.
  • Hillis A, Maguire M, Hawkins BS, Newhouse MM: The Markov process as a general method for nonparametric analysis of right-censored medical data. J Chron Dis 39: 595-604, 1986.
  • Macular Photocoagulation Study Group: Recurrent choroidal neovascularization after argon laser treatment for neovascular maculopathy. Arch Ophthalmol 104: 503-512, 1986.
  • Macular Photocoagulation Study Group: Argon laser photocoagulation for neovascular maculopathy. Three-year results from randomized clinical trials. Arch Ophthalmol 104: 694-701, 1986.
  • Fine SL, Macular Photocoagulation Study Group: Early detection of extrafoveal neovascular membranes by daily central field evaluation. Ophthalmology 92: 603-609, 1985.
  • Macular Photocoagulation Study Group: Changing the protocol: A case report from the Macular Photocoagulation Study. Controlled Clin Trials 5: 203-216, 1984.
  • Macular Photocoagulation Study Group: Argon laser photocoagulation for ocular histoplasmosis: Results of a randomized clinical trial. Arch Ophthalmol 101: 1347-1357, 1983.
  • Macular Photocoagulation Study Group: Argon laser photocoagulation for idiopathic neovascularization: Results of a randomized clinical trial. Arch Ophthalmol 101: 1358-1361, 1983.
  • Macular Photocoagulation Study Group: Argon laser photocoagulation for senile macular degeneration: Results of a randomized clinical trial. Arch Ophthalmol 100: 912-918, 1982.
 
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