Vision does not improve substantially for patients with age-related macular degeneration (AMD) who undergo surgery to remove lesions of new blood vessels, scar tissue, or possible bleeding beneath the retina, according to results of nationwide clinical trials sponsored by the National Eye Institute (NEI), part of the National Institutes of Health.

In older adults, the most common cause of irreversible and severe loss of vision is called wet AMD. Unwanted blood vessels and scar tissue grow beneath and into the macula, the central part of the retina responsible for perceiving fine visual detail. Treatment options for improving vision are limited for wet AMD.

The NEI-funded Submacular Surgery Trials (SST) investigated outcomes of surgery being practiced by retinal surgeons to remove lesions–scientifically known as choroidal neovascularization–that are linked with AMD and other causes. Before the trials began in 1997, the risks and benefits of surgery to improve or stabilize vision of patients with such conditions had not been well defined.

“While the trials were not successful in doing what we wanted to do for these patients with AMD, that is, to keep their vision stable or to improve it,” says NEI Director Paul A. Sieving, M.D., Ph.D., “the study provides valuable information to doctors and their patients. But, we will not stop there. The NEI will continue to conduct and support the best research possible while the search continues for new effective treatments for AMD,” Sieving added.

In the November issue of the journal Ophthalmology, four of a total of six main result papers on the SST will be published. The four papers address surgery for two groups of AMD patients.

In the first group, surgery did not improve vision for half of 454 patients who had centrally located lesions that were not predominantly blood, when compared with half who did not receive surgery but did receive regular eye examinations. This finding confirms a growing clinical impression among many retinal surgeons that submacular surgery is not helpful for these commonly-found lesions in AMD patients’ eyes.

Surgery was also not beneficial for a second group of patients–those with more extensive bleeding under the retina. This second group involved 336 patients who were assigned randomly to either surgery or careful observation. Among these patients, vision had not stabilized or improved after two years in those who underwent surgery to remove lesions and associated blood (which was the primary test of the trials), when compared with patients with no surgery.

Other treatments for CNV due to AMD include laser photocoagulation and photodynamic therapy. Both laser photocoagulation and photodynamic therapy have been shown to reduce the risk of moderate and severe loss of vision in some patients with CNV associated with AMD. But these treatments usually are not used for eye lesions similar to those of patients who took part in the SST.

According to estimates published by the NEI-sponsored Age-Related Eye Disease Study, approximately 200,000 individuals in the United States develop the wet, or neovascular, form of AMD each year. This form occurs in less than 20 percent of all patients with AMD but is responsible for approximately 90 percent of cases with severe vision loss.

The SST built on an hypothesis (emanating from earlier NEI-sponsored SST pilot studies) that surgical removal of CNV lesions may halt enlargement of the visual defect. Further, their removal might spare vital photoreceptors in the central macula from damage and thereby allow nearby ocular structures to function normally.

Patients in the trials also answered questionnaires and surveys to record how their eye condition affected their quality of life, before and after the surgery. Not surprisingly, SST patients reported a high degree of quality of life impairment due to poor vision.

A total of 25 clinical centers collaborated in the trials for the AMD patients with CNV. Two other SST papers, on surgery for CNV due to two causes other than AMD, will be published in the November 2004 Archives of Ophthalmology. The target conditions for those papers were CNV caused by ocular histoplasmosis syndrome or by unknown causes (idiopathic).

More on the 454 patients with AMD-related CNV

• Patients were 50 years or older; median age of 77.
• Each patient had a subfoveal neovascular lesion. The surgeons classified the lesions as ‘classic’ choroidal neovascularization–a pattern seen on photographs of the back of the eye taken as the new blood vessels fill with fluorescein dye.
• Prospective patients with prior treatment for CNV were ineligible.
• All patients, surgery and observation alike, were given follow-up examinations at 3-, 6-, 12-, and 24-month periods after enrollment. Adverse effects were reported immediately following an examination. A separate Adverse Event Review Committee classified such events.
• Rhegmatogenous retinal detachment occurred in twelve surgery eyes and one observation eye.
• Of the surgery patients with no previous cataract surgery, 39 percent received cataract surgery by the 24-month examination, compared with five percent of the observation patients.

More on the 336 patients with more extensive bleeding from AMD

• Patients were 50 years or older with a median age of 79.
• Eligible patients had lesions of 8.9 mm or larger, at least half of which was blood under the center of the macula. They also had best-corrected vision of 20/100 to light perception in the study eye.
• Patients with previous eye treatments with laser photocoagulation were permitted in the trial.
• Two years after surgery, 44 percent of surgery eyes with no prior cataract surgery needed cataract surgery.
• Rhegmatogenous retinal detachment developed in 27 surgery eyes compared with only three of the observed eyes. The SST leadership called this a relatively high level of risk that increased in patients with larger lesions and worse visual acuity levels.”

Journal Citations:

Submacular Surgery Trials (SST) Research Group. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings, SST Report Number 11. Ophthalmology 111: 1967-1980, 2004.

Submacular Surgery Trials (SST) Research Group. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: quality of life findings, SST Report Number 12. Ophthalmology 111: 1981-1992, 2004.

Submacular Surgery Trials (SST) Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings, SST Report Number 13. Ophthalmology 111: 1993-2006, 2004.

Submacular Surgery Trials (SST) Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings, SST Report Number 14. Ophthalmology 111: 2007-2014, 2004.

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Citations

• Hawkins BS, Bressler NM, Miskala PH, Bressler SB, Holekamp NM, Marsh MJ, Redford M, Schwartz SD, Sternberg P Jr, Thomas MA, Wilson DJ, Submacular Surgery Trials (SST) Research Group. Surgery for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration: Ophthalmic Findings, SST Report No. 11. Ophthalmology. 2004 Nov. <a href=’http://www.ncbi.nlm.nih.gov/pubmed/15522362”>PubMed
• Miskala PH, Bass EB, Bressler NM, Childs AL, Hawkins BS, Mangione CM, Marsh MJ, Submacular Surgery Trials (SST) Research Group. Surgery for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration: Quality-of-Life Findings: SST Report No. 12. Ophthalomology. 2004 Nov. PubMed
• Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, MacCumber MW, Marsh MJ, Redford M, Sternberg P Jr, Thomas MA, Williams GA, Submacular Surgery Trials (SST) Research Group. Surgery for Hemorrhagic Choroidal Neovascular Lesions of Age-Related Macular Degeneration: Ophthalmic Findings: SST Report No. 13. Ophthalmology. 2004 Nov. PubMed
• Childs AL, Bressler NM, Bass EB, Hawkins BS, Mangione CM, Marsh MJ, Miskala PH, Submacular Surgery Trials (SST) Research Group. Surgery for Hemorrhagic Choroidal Neovascular Lesions of Age-Related Macular Degeneration: Quality-of-Life: SST Report No. 14. Ophthalmology. 2004 Nov. <a href=’http://www.ncbi.nlm.nih.gov/pubmed/15522365’”>PubMed