Diagnosing early-stage AMD with a dark adaptation device

Age-related macular degeneration (AMD) is a complex and progressive disease that may lead to blindness if left untreated. Thus, early diagnosis is essential in order to limit or slow vision loss. The diagnosis of AMD is typically based on a routine dilated eye exam and information obtained from optical coherence tomography (OCT).

Unfortunately, diagnosing early-stage AMD can present a challenge because these patients are often asymptomatic, have good corrected visual acuity and a normal retina. Consequently, a routine vision test may not raise any suspicion of the disease.

Dark adaptation as an indicator of AMD

A useful test for the detection of early AMD is dark adaptation (DA). Simply defined as the recovery of vision when going from daylight to darkness, DA has been shown to be a sensitive biomarker for AMD, even in its earliest stages.¹

Studies also indicate that DA is severely impaired in patients who have normal visual acuity.^2-4 However, despite its link to early AMD, DA testing is largely underused in clinical practice, perhaps due to the fact that traditional methods of measuring DA impairment can take up to an hour to complete.

To overcome the problems associated with traditional DA testing, a dark adaptometer known as the AdaptDx (MacuLogix Inc) was developed as a screening tool for AMD, retinitis pigmentosa and other macular degenerations. The device can aid in the diagnosis of early-stage, or subclinical, AMD before visual loss occurs and even before structural changes are observed, and adds to the information obtained from retina cameras and OCT imaging.

The adaptometer measures the rod intercept (RI) as an indicator of impaired DA; RI is the recovery time of scotopic sensitivity to a benchmark level, providing an objective and sensitive measurement of retinal function. An RI below 6.5 minutes is normal. An RI greater than 6.5 minutes is an early indicator of retinal disease, requiring additional testing.

The test can be easily performed and takes as little as 5 minutes per eye with no need for pre-adaptation or pupil dilation. Findings from a clinical study that included two cohorts of elderly adults, 127 with early-to-advanced AMD and 21 with normal retinas (as determined by fundus photography grading), showed that the adaptometer had a diagnostic sensitivity and specificity of 90.6% and 90.5%, respectively.

Additionally, the device demonstrated excellent reliability with a test-retest agreement of 94.7% between the first and second visits.⁴

Research findings

I recently collected data for six patients (aged 60 to 75 years) who were known before DA testing with the device to have AMD.  Five of the six patients had a corrected visual acuity of 10/10 P2 in both eyes (except one who was monophthalmic); the other patient had a corrected visual acuity of 6.3/10 P2 in both eyes.

As expected, all six patients had severely impaired dark adaptation (an RI greater than 6.5 minutes in one or both eyes) consistent with AMD. This is perhaps not surprising given that drusen cause degeneration of retinal pigment epithelium cells, which may in turn cause hypoxia and mechanical stress to the photoreceptors.

More interestingly, I also undertook a consecutive case series study that included 16 patients (aged 60 to 80 years) who presented with normal retinal health based on clinical examination. Of these 16 clinically normal patients, 10 were confirmed to be AMD-free by DA (an RI of less than 6.5 min in both eyes) but six were discovered to have subclinical AMD (an RI greater than 6.5 min in one or both eyes). 

Thus, a surprising 38% (six of 16) of the patients with clinically normal retinal health actually had undiagnosed AMD. Although this was only a small study, these findings are important because they highlight that early-stage AMD cannot and should not be ruled out in older patients with a normal retina examination and good visual acuity.

The adaptometer in daily clinical practice

The dark adaptometer has been validated in clinical studies involving more than 1,000 patients, with additional studies ongoing. The device is also being used by a number of pharmaceutical companies in the development of drugs for early AMD and is proving to be a valuable research tool.

However, equally important is its use in daily clinical practice. Currently, in my practice, I use OCT and autofluorescence to diagnose AMD. To date, I have only used the AdaptDx in clinical studies; however, I feel the device will be useful in helping us to identify early AMD patients and individuals who have a high probability of going on to develop the disease.

This will allow us to guide the patient in taking preventative lifestyle measures. The only limitation in identifying early AMD is that we do not yet have drugs that can prevent disease progression. While this may seem frustrating at first for clinicians and patients alike, we can use this information to justify appropriate lifestyle modifications, such as weight loss, smoking cessation, eye health supplements and increased consumption of leafy green vegetables.

Once AMD is detected, the adaptometer can be used to monitor disease progression so that we can intervene before vision loss occurs. Additionally, if we can further demonstrate a role for vitamins and antioxidant therapy in the prevention of AMD, using DA impairment testing to identify patients who are likely to develop AMD will be very valuable.

References

1. Owsley C, et al. Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration. Ophthalmology. 2016;123:344-351.

2. Owsley C, et al. Psychophysical evidence for rod vulnerability in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2000;41:267-273.

3. Owsley C, et al. Delays in rod-mediated dark adaptation in early age-related maculopathy. Ophthalmology. 2001;108:1196-1202.

4. Jackson GR, et al. Diagnostic sensitivity and specificity of dark adaptometry for detection of age-related macular degeneration. Invest Ophthalmol Vis Sci. 2014;55:1427-1431.

Professor David Gaucher, MD

E: david.gaucher@chru-strasbourg.fr

Professor Gaucher is based at the Department of Ophthalmology, University Hospital of Strasbourg, France. Prof. Gaucher has no financial interests in MacuLogix Inc.