FDA UPDATE: Contrast Sensitivity Testing Standards
Worldwide protocols could be adopted this year.
BY DAVID W. EVANS, PH.D.

As a means to evaluate the quality-of-vision outcomes of today's advanced refractive and IOL implant surgery beyond Snellen visual acuity, the FDA has been requiring companies introducing new technologies to evaluate patient contrast sensitivity during clinical trials.

The FDA subcommittee on vision standards evaluated the many types of contrast sensitivity tests, and in 2003 finalized its recommendations for evaluating quality of vision in clinical trials. Of the three types of contrast sensitivity tests, it was determined that contrast sensitivity testing with sine-wave gratings was the most sensitive for this purpose. Letter contrast sensitivity tests (such as Pelli-Robson or Rabin) and low contrast acuity tests (such as 5% or 10% contrast acuity) were rejected as not testing across a wide enough range of visual sensitivity to be appropriate as the primary outcome measure in clinical trials. The FDA also established test protocols, which have been used in FDA clinical trials by every company developing new ophthalmic devices for refractive surgery during the past 3 to 5 years. Each patient is tested using four spatial frequencies of sine-wave gratings, under photopic (85 cd/m²) and mesopic (3 cd/m²) test lighting conditions. In addition to standard mesopic testing, patients are also tested under mesopic conditions with glare.

Taking these efforts a step further, the agency has been working with the International Standards Organization (ISO) and the American National Standards Institute (ANSI) to establish worldwide regulatory standards for vision testing and other criteria related to clinical trials. ANSI and ISO are expected to vote on the standards early this year.

The Latest Developments

Two recent developments in the process of creating standards have been:

Reconsideration of low contrast acuity testing. In May, Navy Capt. Steven Schallhorn, M.D., presented data from his ongoing studies to the FDA subcommittee. Dr. Schallhorn has tested thousands of Navy refractive surgery patients to evaluate their postoperative quality of vision and its relationship to everyday real-world performance.

He recommended, as did the FDA subcommittee, that letter contrast sensitivity tests should not be used for evaluating the quality of vision. He has stopped using letter contrast sensitivity tests in his studies. He has chosen to use low contrast testing: a 5% contrast acuity test for the photopic condition and a 25% contrast acuity test for the mesopic condition. Dr. Schallhorn reported that he was able to obtain better data with the low contrast acuity tests than with sine-wave grating tests. In addition, he found low contrast acuity tests to be more easily integrated into the clinical setting.

In response to Dr. Schallhorn's recommendations, the FDA subcommittee, at its meeting in September, added low contrast acuity testing as an adjunct in clinical trials, but not as a replacement for sine-wave grating tests. The subcommittee recommended a 10% contrast acuity test for both photopic and mesopic conditions. The 10% tests represent a middle ground, and the largest amount of published data is based on the 10% tests. Many of the companies evaluating new ophthalmic devices in clinical trials have added testing of 10% contrast acuity to their test protocols.

Consideration of the bull's-eye sine-wave grating test. Another type of contrast sensitivity test that has garnered recent attention is the two-dimensional sine-wave test, developed by Jack Holladay, M.D., and M&S Technologies Inc. This test, which presents sine-wave gratings in a circular format, appears as a bull's-eye pattern. The rings of the bull's-eye are presented at different contrast levels, and the patient indicates the lowest contrast level when he or she can see the circular patterns. A computer video system is used to administer the test to patients, unlike the other tests used in clinical trials, which present test stimuli in standardized backlit systems. This test has been purported to have benefits over one-dimensional sine-wave grating tests. Because the currently used sine-wave tests present gratings only in the vertical orientation, a multidimensional test could potentially be used to evaluate vision losses that occur in specific nonvertical orientations, such as may be caused by higher-order aberrations like coma or trefoil.

The application of this new bull's-eye test to clinical trials was discussed at the most recent FDA subcommittee meeting. Committee members felt there may be some future applicability of this type of test, but further data in controlled clinical trials would be needed. It is unclear whether a vision loss in only one orientation, such as caused by coma, could be accurately measured by a bull's-eye type of test. Since this new test measures sensitivity in all orientations simultaneously, a patient who has the ability to see well at one orientation might obtain a good score on the bull's-eye, but actually have poor quality of vision due to vision losses at other orientations. It may be necessary to present sine-wave patterns at specific orientations to determine the quality of vision at those orientations.

Further data will provide insight into these questions and whether orientation-specific losses related only to trefoil and coma play a major role in the overall patient quality of vision. At the next annual meeting of the American Society of Cataract and Refractive Surgery, Dr. Holladay plans to present a normative data study on this testing method. "The data will show that with the sinusoidal bull's-eye target and threshold strategy, we are able to achieve a precision of 0.1 log units (1 dB), which is 3 times more sensitive than current systems," he said.

What's Next?

At this time, sine-wave grating patterns remain the primary test required by the FDA for clinical trials evaluating the quality of vision associated with new refractive surgery technology. Low contrast letter acuity using a 10% contrast acuity test can be added as an adjunct test of visual quality, but not as a replacement for the sine-wave tests. Tests of letter contrast sensitivity are not recommended by the FDA, and the new bull's-eye test needs further evaluation.

ANSI and ISO are expected to vote early this year on whether to enact those standards worldwide, and will likely turn its attention next to the question of whether special testing standards are needed to measure the results of wavefront-guided refractive surgery.

David W. Evans, Ph.D., is a member of the FDA subcommittee on vision standards. He obtained his Ph.D. in ocular physiology from Indiana University and is a consultant faculty member at the University of Alabama, Birmingham. He has a financial interest in the VectorVision CSV-1000 contrast sensitivity testing instrument.