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Krypton-Argon Regression of Neovascularization Study (KARNS)

Purpose | Background | Description | Patient Eligibility | Recruitment Status | Current Status | Results | Publications | Resource Centers | NEI Representative



The KARNS was a randomized clinical trial designed to compare the effectiveness of argon and krypton laser photocoagulation in causing the regression of preexisting neovascularization on the disc (NVD) in diabetic retinopathy. The main theoretical advantage for the krypton laser in the treatment of diabetic retinopathy is that the red laser beam penetrates blood and may be more effective in making burns in the pigment epithelium in eyes with vitreous hemorrhage.

The burns produced by the krypton laser in the retina are different from those produced by the argon laser. Specifically, the burns from the krypton laser do not involve the inner retina. Also, the krypton laser spares the nerve fiber layer near the macula. In contrast, nerve fiber layer burns are common with the argon laser. Pigment epithelium and outer segments are usually destroyed by both krypton and argon photocoagulation, but there is no uptake of energy by the vascular tissues within the retina when krypton photocoagulation is used. Further, krypton treatment is more effective in penetrating nuclear sclerosis of the lens and can be used to treat some diabetic eyes with this condition that cannot be treated with the argon laser.


In the KARNS, patients with diabetic retinopathy and NVD of one-third disc area or greater in extent were assigned at random to either argon or krypton laser scatter photocoagulation (panretinal photocoagulation). The null hypothesis was that each treatment would result in a similar proportion of eyes having regression of the NVD by 3 months. The KARNS pilot study affirmed the benefits of argon laser photocoagulation in the treatment of proliferative diabetic retinopathy, as demonstrated in the NEI-supported Diabetic Retinopathy Study conducted a decade ago. (See publication list.) The KARNS study sought to determine whether use of the krypton laser could be as effective as the argon laser in causing regression of diabetic neovascularization, but with fewer side effects (such as smaller loss of central visual acuity).

Thirty-two nationwide clinical centers participated initially in this multicenter clinical trial. Following the initial study examination, the baseline examination and fundus photographs were obtained within 1 week before application of photocoagulation. Study followup visits occurred at 3 months and 1 year after entry in the study. Additional visits were scheduled as clinically necessary.

The specific techniques for photocoagulation were similar for both argon and krypton scatter photocoagulation. Scatter (panretinal) photocoagulation consisted of 1,600 to 2,000 burns placed 0.5 to 1 burn width apart. Burns of moderate intensity (whiteness) and 500 µm in size at the retina were required. The burns were applied to the retinal periphery no closer than 2 disc diameters from the center of the fovea and 500 µm from the margin of the optic disc.

In December 1985, the Early Treatment Diabetic Retinopathy Study groups reported that focal photocoagulation was effective in reducing the rates of moderate visual loss in patients with clinically significant diabetic macular edema. The KARNS protocol was then changed to allow focal treatment for clinically significant macular edema in all study participants and to allow an eye that had previous focal photocoagulation for macular edema to become eligible for study.

The study primary end point was regression of NVD, as assessed on the 3-month visit stereo fundus photographs of the disc, to less than one-third disc area in extent. Secondary end points included change in extent of NVD, change in visual acuity after photocoagulation, development of fibrous tissue proliferation, and change or development of macular traction lines.

Patient Eligibility

Men and women ages 18 through 79 diagnosed with diabetes mellitus and who had neovascularization on the optic nerve head (NVD) were eligible. NVD in one or both eyes of each patient had to be greater than or equal to DRS Standard Photograph 10A. NVD was defined as new vessels on the surface of the retina, further forward in the vitreous cavity over the disc, or within one disc diameter of the disc in any direction. Patients' ocular media must have been clear enough for fundus photography, which allowed the extent of neovascularization on the optic nerve head to be assessed. (If vitreous hemorrhage or other media opacity prevented adequate visualization of the neovascularization, it would greatly impair the ability to assess the effect of photocoagulation.) Another requirement for patient eligibility was the presence of an area of at least three quadrants of the retina in which full argon or krypton laser panretinal photocoagulation could be placed. (Vitreous hemorrhage and/or traction retinal detachment that interfered with treatment was less than one quadrant in extent.)

Patient Recruitment Status

Recruitment began in December 1984 and was completed in June 1990. A total of 1,053 eyes of 798 patients were enrolled.

Current Status of Study

Completed. Patient followup concluded in June 1991.


After excluding the eight clinics with inadequate followup, a total of 907 eyes (696) patients seen at 24 clinical centers were available for study analyses. Of these patients, 211 had both eyes enrolled in the study. A total of 453 eyes were randomly assigned to argon treatment and 454 eyes to krypton treatment.

For the primary study end point, regression of NVD to less than one-third disc area in extent at the 3-month followup visit, there was no statistical difference between treatment groups (41.1 percent of eyes assigned to argon versus 41.8 percent of eyes assigned to krypton scatter photocoagulation had this degree of regression; p = 0.92. At the 1-year followup visit, the proportion of eyes with this degree of regression increased, but again there was no statistical difference between treatment groups, respectively; p = 0.58.

The 3-month and 1-year fundus photographs were compared side by side with the baseline photographs to assess change in the extent of NVD. At the 3-month visit, a decrease in NVD was seen in 76 percent of eyes assigned to the argon group and 77 percent of eyes assigned to the krypton group. The NVD had shrunk to less than half of its original extent in 54.8 percent and 54.0 percent of the argon- and krypton-treated groups, respectively. An increase in NVD at 3 months was seen in 9.2 percent of eyes assigned to the argon group and 9.9 percent of eyes assigned to the krypton group.

The KARNS results demonstrate that moderate and large differences between argon and krypton scatter photocoagulation for NVD in proliferative diabetic retinopathy are unlikely. There is little if any difference in the clinical effect of these two wavelengths of lasers in causing regression of diabetic neovascularization. Because the lasers appear equally effective for the treatment of proliferative diabetic retinopathy, the choice of laser should be based on relevant clinical features. Argon scatter photocoagulation may be preferred for most patients because it seems to be less painful. However, for eyes with some vitreous hemorrhage, nuclear sclerosis, or other media opacities, where krypton seems to penetrate better, it may be the treatment of choice.

The method of creating photocoagulation burns seems to make little if any difference in the treatment of proliferative diabetic retinopathy, but there is a large difference between scatter photocoagulation and no photocoagulation. Eyes with high-risk proliferative diabetic retinopathy should receive scatter photocoagulation however it can be accomplished.


Chey EY for the, The Krypton Argon Regression Neovascularization Study Research Group: Randomized comparison of krypton versus argon scatter photocoagulation for diabetic disc neovascularization: KARNS Study Report Number 1. Ophthalmology 100: 1655-1664, 1993.

Ferris FL, Ferris FL, Ferris FL, Singerman LJ: Inexpensive collaborative research. Invest Ophthalmol Vis Sci 24 (suppl), 1983.

Davis MD, Singerman LJ, Ferris FL III, Passloff RW: Red krypton laser (RKL) versus blue-green argon laser (BGAL) treatment of proliferative diabetic retinopathy (PDR) with neovascularization of the disc (NVD). Invest Ophthalmol Vis Sci 24 (suppl), 1983.

Resource Centers

Co-Chairmen's Offices
Frederick L. Ferris III, M.D.
National Eye Institute
National Institutes of Health
Building 31, Room 6A24
31 Center Drive, MSC 2510
Bethesda, MD 20892-2510
Telephone: (301) 496-6583

Lawrence J. Singerman, M.D.
Retina Associates of Cleveland, Inc.
26900 Cedar Road, Suite 323
Cleveland, OH 44122
Telephone: (216) 831-1959

NEI Representative

Frederick L. Ferris III, M.D.
National Eye Institute
National Institutes of Health
Building 31, Room 6A24
31 Center Drive, MSC 2510
Bethesda, MD 20892
Telephone: (301) 496-6583
Fax: (301) 496-2297

Last Updated: 10/23/99

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