Contrast Sensitivity: Evaluating Drug Response
It's a useful tool for measuring the efficacy of glaucoma and AMD treatments.
BY DAVID W. EVANS, PH.D., M.B.A.

The introduction of new drugs to treat ocular disease has exploded in the past 3 to 5 years.

But diagnostic tools for monitoring the efficacy of new treatments for glaucoma and AMD haven't kept up with the pace of change.

Visual field testing has been shown to be relatively insensitive for tracking short-term (less than a year) glaucomatous changes in visual function. For AMD, visual acuity remains the staple for assessing progression or regression of the disease. Visual acuity is an excellent tool for prescribing glasses, but was never designed for managing treatment regimens for ocular disease patients.

Contrast sensitivity (CS) testing is best known for objectively measuring quality of vision, not only for refractive surgery but also for cataracts, posterior subcapsular opacification and multifocal IOLs. Indeed, the FDA now has specific requirements for CS testing in clinical trials designed to evaluate new ophthalmic devices. Ophthalmologists have used CS testing for over two decades to document the vision loss associated with cataracts and the need for surgery.

But there's another side to CS testing. This tool is very powerful for tracking changes in vision related to drug treatment. It offers feedback about drug response that greatly aids ophthalmologists in managing treatment regimens. This article explores the usefulness of contrast sensitivity testing for tracking drug efficacy, and how you can use this tool in managing treatment more efficiently.

Managing Glaucoma

Glaucoma is a disease that affects the health of the ganglion cells. During the disease process, numerous ganglion cells perish, leading to the excavation of the optic nerve head. The vast majority of the ganglion cells reside in the central 3 degrees. In fact, the density of ganglion cells in central vision is 70 times higher than at 20 degrees eccentricity, where the earliest glaucomatous vision loss is typically detected with a nasal step.

It stands to reason that a glaucoma treatment that prevents damage to the ganglion cells, whether through reduced IOP, increased blood flow, or neuroprotection, would have a much greater effect in central vision. Studies have confirmed this. Substantial increases in CS following the reduction of IOP through drug treatment or trabeculoplasty are well-documented. Also, data show that drug regimens that increase ocular blood flow in glaucoma patients are associated with a concomitant increase in contrast sensitivity. Recently, an ocular hypotensive drug with neuroprotective qualities was shown to provide a larger increase in contrast sensitivity than a drug with the same level of IOP reduction, but with no reported neuroprotection.

From a patient management standpoint, these improvements in vision are very useful. Changes in CS occur within a month following treatment, and then continue over a 6-month period, assuming the patient is properly medicated.

This short-term feedback on patient response provides a unique tool for disease management. You can treat the patient and then evaluate the improvement in central vision to determine the efficacy of drug therapy. As with any type of threshold test, there is some variability. Therefore, the recommended amount of change to look for is a 0.3 log unit change in CS. This change is large enough to be beyond the typical variation of testing. A 0.3 log unit change equates to a two-level change on the commercially available contrast sensitivity systems, such as the CSV-1000 from VectorVision or the FACT chart from Stereo Optical. The most common change with glaucoma occurs at 12 cycles per degree, which is Row C on the VectorVision CSV-1000.

CS Adds Information

Using CS to manage drug treatment in glaucoma patients is particularly useful when IOP or other measures provide limited information. For example, for some patients who have normal tension glaucoma, IOP treatment isn't expected to reduce the pressure more than a few mmHg. It's sometimes difficult to determine the proper target pressure. In these cases, the level of treatment (which drug, combination of drugs or what concentration to use) can be titrated by monitoring the improvement in central vision. The patient is treated, and normally an improvement is noted after a month. If no change occurs after the second month, treatment must be modified. The failure of a drug to control glaucoma can also be more directly managed.

Decreases in contrast sensitivity are also an aid in patient management. A fall in contrast sensitivity of two contrast levels from one visit to the next may imply that the treatment is no longer effective. Of course, the presence of a cataract or other ocular problem must be ruled out.

These reductions in CS can occur even in cases where the patient has shown a reduction in IOP to the target level. In many cases, reduced CS during the course of treatment will precede changes in other measures, particularly IOP and visual field testing. The patient may have diurnal IOP spikes that aren't detected during the office visit. Visual field results are notoriously insensitive to short-term changes in vision when treatment is faltering.

Monitoring with CS is particularly useful in cases where there is an IOP-independent medication, such as treating for ocular blood flow with a calcium channel blocker or a neuroprotective drug. The improvements in contrast sensitivity can be used to determine the efficacy of the drug, regardless of whether there is any change in IOP. In some cases, such as in treatment for ocular blood flow, the IOP may fall with treatment, but a concomitant reduction in CS indicates the drug treatment isn't appropriate. Another important benefit from a patient management standpoint is that the improvements can be used to educate patients on the need for compliance. Showing a patient the improvement with treatment provides more motivation for the patient to consistently take the drug.

Monitoring AMD

Contrast sensitivity can also be utilized to manage patients with AMD. Effective treatment regimens early in the disease state, particularly nutritional therapy, rely on early detection and the ability to track subtle changes in vision. It isn't unusual for a patient to demonstrate a loss in CS while still retaining good acuity. Then, after several months of nutritional supplement therapy, CS recovers.

In AMD, the time frames for recovery are longer than for glaucoma, and in most cases not as clearly defined. Nutritional therapy doesn't directly target the eye, as does glaucoma therapy, and other factors are involved. If nutritional therapy is beneficial, a response is normally seen within 3 months. If no response is seen, modification of therapy may be needed.

Use of CS greatly aids in patient communication, a key component of practice efficiency. Because there are no direct treatments for early AMD, nutritional therapy is sometimes the only option. The ability to track the effects of the therapy allows the clinician to directly educate the patient on the response and benefit of therapy. As in glaucoma treatment, this communication with the patient increases compliance. Further, because many nutritional therapies aren't covered by insurance or Medicare, tracking the beneficial effects provides justification for the cost incurred by the patient.

For advanced AMD, new treatment options are becoming available. Contrast sensitivity testing is useful for tracking the response, as many patients show improvements with treatment before changes in acuity are noted. It's important to keep in mind that many patients with advanced AMD have very poor vision, worse than 20/70. Most CS tests are designed for patients with relatively good vision. Therefore, when tracking treatment for advanced disease, it's best to use a CS test specifically designed for patients with poor vision, such as the Pelli-Robson or certain versions of the VectorVision CSV-1000 test. Or, to compensate for the poor vision, you can shorten the testing distance to half of the normal distance.

Dr. Evans is a consultant faculty member at the University of Alabama, Birmingham, and a member of the FDA subcommittee on vision standards. He's been involved in contrast sensitivity research since 1978 and has written extensively on contrast sensitivity and its relationship to ocular disease and refractive surgery. He has a financial interest in the CSV-1000 standardized contrast sensitivity device marketed by VectorVision, Inc.