AMD DIAGNOSIS GOES DARK

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Impaired dark adaptation in AMD patients appears even before there are clinically visible signs.

An estimated 1.8 million Americans aged 40 and older already have age-related macular degeneration (AMD), according to the Centers for Disease Control and Prevention. An additional 7.3 million with large drusen are at substantial risk for vision loss.

Even so, the prevalence of AMD remains under diagnosed. One cross-sectional study, for example, found that primary eyecare providers, both optometrists and ophthalmologists, missed one in four cases of AMD.[1]

That finding isn’t entirely surprising given that individuals often experience night vision problems early in the disease process, a finding that doesn’t show up when measuring high-contrast Snellen acuity or structural imaging technology. However, we now can objectively measure dark adaptation, the time it takes for the eye to adjust from bright light to darkness, known as dark adaptation, to diagnose individuals with AMD as many as three years before any visible clinical findings.

NONINVASIVE TEST
The AdaptDx from Maculogix, Inc. is a non-invasive tabletop instrument that can measure dark adaptation rapidly. Gregory Jackson, PhD, co-founder and chief technology officer of Maculogix, was the principal inventor. While I was still teaching at University of Alabama at Birmingham, my colleagues at the optometry clinic and I became among the first doctors to use the device.

In a darkened room, patients rest their chin and forehead on supports similar to those of other ophthalmic instruments. The AdaptDx presents a brief camera-like flash to bring the patient to a light-adapted state. It then presents a bleaching stimulus just above the macula, then the detection stimuli become progressively dimmer. The patient presses a handheld response button when a stimulus light appears.

At the end of the test, the AdaptDx uses a plot to calculate rod intercept time (RIT), which is the number of minutes at which the visual sensitivity recovery crosses three log units of recovery. At this point, recovery of visual sensitivity is completely rod-mediated, hence the term “rod intercept.” The rod intercept characterizes dark adaptation speed.

To date, patients tested with AdaptDx in clinical studies are past age 50, the same threshold as the Age-Related Eye Disease Study, or AREDS. In the future, we might consider testing patients aged 40 and above with risk factors for AMD, including family history and lifestyle.

SIX-MINUTE ANSWER
The original testing protocol was about 20 minutes, but we now know that a rod intercept time of less than 6.5 minutes is normal, while a rod intercept time greater than 6.5 minutes is an early indicator of retinal disease.

In the earlier stages of AMD, a patient can takes three times longer to adapt than a patient without AMD. Patients in the later stages of AMD can take 10 times longer.

To be sure, impaired dark adaptation is the first detectable consequence of emerging AMD. Impaired dark adaptation is not a risk factor for AMD; instead it is the earliest manifestation of AMD.

The Alabama Study on Early Age-Related Macular Degeneration, or ALSTAR Study, a prospective study of subclinical AMD, looked at 325 adults without clinically detectable AMD.2 At baseline, 24% of the subjects exhibited impaired dark adaptation. Results showed that impaired dark adaptation identifies subclinical AMD at least three years before it can be seen with standard clinical methods. That means the patient may have clinical AMD even in the absence of telltale drusen or changes in the retinal pigment epithelium.

Furthermore, ALSTAR shows, individuals with impaired dark adaptation were twice as likely to develop clinically evident AMD and eight times as likely to advance beyond the earliest stage of AMD. More recently, evidence has been reported that subclinical drusenoid deposits (SDDs) are consistent with prolonged dark adaptation but not by other sophistocated measures except dark adaptation.3 Eyes with clinically normal ocular health and early AMD who have been identified with SDDs warrant careful scrutiny because of their increased risk for incident early AMD and its progression.

START THE CONVERSATION
At this point, further testing is warranted. Once you’ve identified a patient with impaired dark adaptation, use those results to start a conversation with the patient. Ask patients about such questions as lifestyle, smoking, exposure to sunlight and family history of AMD.

While you can’t change certain risk factors, you can modify others. For example, you can encourage the patient to quit smoking. You might also recommend dietary changes and use of a supplement containing the AREDS or AREDS2 formula. If your practice offers genetic testing, you might want to recommend that to the patient as well.
Consider this example: A patient presents complaining about poor night vision, and the rod intercept is 8.2 minutes. You instruct the patient to return in two weeks for further testing, including optical coherence tomography, at which time there are no visible drusen.

You diagnose the patient with subclinical AMD and recommend lifestyle changes, dispense nutraceuticals and provide eyewear to protect against ultraviolet radiation and blue light. The patient returns for follow-up every six months and, as dark adaptation worsens and drusen become more prominent, every three months. Four years later, you identify early choroidal neovascularization and refer the patient to a retinal
specialist.

Your timely referral has saved this patient’s vision. In addition, you’ve seen the patient more often to provide medically necessary testing, dispense items that can help prevent vision loss and, in the process, distinguished your practice.

DELAY VISION LOSS
As life expectancy continues to increase, we can expect many more individuals to suffer vision loss due to age-related macular degeneration. Obviously no patient wants to lose vision, especially if we can work with the majority of AMD patients who have the dry, or nonexudative form, and delay their vision loss as much as possible. Besides the benefits to your patients, you also have a way of making your practice stand out.

Leo P. Semes, OD, FAAO, a former Professor of Optometry at UAB, has authored more than 250 articles, book chapters and posters and is principal author of the AOA’s Clinical Practice Guideline, Care of the Patient with Ocular Surface Disorders. He is a founding member of the Optometric Glaucoma Society and a founding fellow of the Optometric Retina Society. Semes is a speaker for Maculogix.

  1. Neely DC, Bray KJ, Huisingh CE, et al. Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care. JAMA Ophthalmol 2017 Jun 1;135(6):570-5.
  2. Owsley C, McGwin G Jr, Clark ME, et al. Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration. Ophthalmology 2016 Feb;123(2):344-51.
  3. Neely D, Zarubina AV, Clark ME, et al. Association Between Visual Function and Subretinal Drusenoid Deposits in Normal and Early Age-Related Macular Degeneration Eyes. Retina. 2017 Jul;37(7):1329-36.
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