Reflections on early detection of AMD

Joseph Hallak

In the last a few decades there has been a flurry of newer tests trying to build on some physiological properties of vision. The goal is to predict the onset of the pathology sometimes by a few years.

A recent article in Primary Care Optometry News presented a case where a dark adaptation test (“Routine visit leads to asymptomatic diagnosis,” March 2019, pages 23, 21 and 22) was used. The author, Amanda S. Legge, OD, postulated that “dark adaptation is the only biomarker for early AMD,” and that any significant change detected is considered to be predictive of age-related macular degeneration.

Owsley and colleagues reported on a study of dark adaptation in adults older than 60 years of age, concluding that subjects with significant delayed dark adaptation are two times more at risk for AMD as early as 3 years ahead of time. According to the authors, even though AMD affects the cone receptors, delayed rod-mediated dark adaptation is related to mechanisms of translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch’s membrane, hence the early predictive correlation to AMD.

In a PCON editorial, Dr. Michael DePaolis noted that dark adaptation may be a reliable biomarker for AMD (“Abnormal dark adaptation: An early biomarker for AMD,” January 2017, page 4).

MacuLogix claims that its AdaptDx has 90% sensitivity and 90% specificity, would take around 20 minutes to finish and can predate the diagnosis of clinically evident AMD by about 3 years in some patients, according to the ALSTAR study (Owsley et al.).

Other tests, such as microperimetry and hyperacuity perimetry, subjectively test for AMD and can detect localized functional changes.

Wu and colleagues studied the impact of reticular pseudodrusen on visual function using mfERG and microperimetry. The presence of reticular pseudodrusen in intermediate AMD was not associated with mfERG response amplitude or microperimetry. Attention is now turned to focal cone ERG (Wood et al.).

However, recent and not-so-recent advancements in OCT testing are now quick, precise and patient-friendly. Fundus autofluorescence tests, for example, indicate early or late stages of AMD in one quick and patient-friendly test.

OCT angiography is one of the latest advances in OCT imaging with clinical implications. Its use is not yet widespread but it is on its way to refining diagnoses of vascular abnormalities and blood flow in diabetes, glaucoma and macular degeneration (de Carlo et al.).

Early on, attention turned to lipofuscin and drusen, followed by AREDS 1 and 2 recommendations to delay progression. Now a retina specialist will look at OCT, drusen and breaks in retinal outer layers and beyond. Only if there is a break and leakage will some form of medical intervention be considered.

In summary, the practical clinical point is this: You predict, follow up and intervene. A 3-year prediction of AMD, many years ahead of, say, glaucoma, and genetic predisposition for major chronic diseases years ahead are great, albeit worrisome and sometimes unwelcome, popular tools. However, one has to wonder about the present practical clinical value to the primary care doctor. It is good to have a dark adaptation test lasting 20 or more tedious minutes to counsel the patient, but it is more important to conduct a quick OCT test to monitor, treat and manage AMD. The immediate clinical dispositions are to establish the frequency of follow-up visit, properly counsel the patient and judiciously refer for management and treatment. These points can be gleaned and inferred from the case analysis of Dr. Legge mentioned above. However, our objective here is to group and highlight them with the goal of practical clinical disposition.


References:

De Carlo T, et al. International Journal of Retina and Vitreous. 2015;doi.org/10.1186/s40942-015-0005-8.

Jackson GR, et al. Invest Ophthalmol Vis Sci. 2014;doi:10.1167/iovs.13-13745.

Owsley C, et al. Ophthalmology. 2016;doi.org/10.1016/j.ophtha.2015.09.041.

Wood A, et al. PLoS One. 2014;doi:10.1371/journal.pone.0096742.

Wu Z, et al. Invest Ophthalmol Vis Sci. 2014;doi:10.1167/iovs.14-14407.


For more information:

Joseph Hallak, OD, PhD, FAAO, is in private practice in Syosset, N.Y. He can be reached at drjhallak@aol.com.


Disclosure: Hallak reports no relevant financial disclosures.

Joseph Hallak

In the last a few decades there has been a flurry of newer tests trying to build on some physiological properties of vision. The goal is to predict the onset of the pathology sometimes by a few years.

A recent article in Primary Care Optometry News presented a case where a dark adaptation test (“Routine visit leads to asymptomatic diagnosis,” March 2019, pages 23, 21 and 22) was used. The author, Amanda S. Legge, OD, postulated that “dark adaptation is the only biomarker for early AMD,” and that any significant change detected is considered to be predictive of age-related macular degeneration.

Owsley and colleagues reported on a study of dark adaptation in adults older than 60 years of age, concluding that subjects with significant delayed dark adaptation are two times more at risk for AMD as early as 3 years ahead of time. According to the authors, even though AMD affects the cone receptors, delayed rod-mediated dark adaptation is related to mechanisms of translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch’s membrane, hence the early predictive correlation to AMD.

In a PCON editorial, Dr. Michael DePaolis noted that dark adaptation may be a reliable biomarker for AMD (“Abnormal dark adaptation: An early biomarker for AMD,” January 2017, page 4).

MacuLogix claims that its AdaptDx has 90% sensitivity and 90% specificity, would take around 20 minutes to finish and can predate the diagnosis of clinically evident AMD by about 3 years in some patients, according to the ALSTAR study (Owsley et al.).

Other tests, such as microperimetry and hyperacuity perimetry, subjectively test for AMD and can detect localized functional changes.

Wu and colleagues studied the impact of reticular pseudodrusen on visual function using mfERG and microperimetry. The presence of reticular pseudodrusen in intermediate AMD was not associated with mfERG response amplitude or microperimetry. Attention is now turned to focal cone ERG (Wood et al.).

However, recent and not-so-recent advancements in OCT testing are now quick, precise and patient-friendly. Fundus autofluorescence tests, for example, indicate early or late stages of AMD in one quick and patient-friendly test.

OCT angiography is one of the latest advances in OCT imaging with clinical implications. Its use is not yet widespread but it is on its way to refining diagnoses of vascular abnormalities and blood flow in diabetes, glaucoma and macular degeneration (de Carlo et al.).

Early on, attention turned to lipofuscin and drusen, followed by AREDS 1 and 2 recommendations to delay progression. Now a retina specialist will look at OCT, drusen and breaks in retinal outer layers and beyond. Only if there is a break and leakage will some form of medical intervention be considered.

In summary, the practical clinical point is this: You predict, follow up and intervene. A 3-year prediction of AMD, many years ahead of, say, glaucoma, and genetic predisposition for major chronic diseases years ahead are great, albeit worrisome and sometimes unwelcome, popular tools. However, one has to wonder about the present practical clinical value to the primary care doctor. It is good to have a dark adaptation test lasting 20 or more tedious minutes to counsel the patient, but it is more important to conduct a quick OCT test to monitor, treat and manage AMD. The immediate clinical dispositions are to establish the frequency of follow-up visit, properly counsel the patient and judiciously refer for management and treatment. These points can be gleaned and inferred from the case analysis of Dr. Legge mentioned above. However, our objective here is to group and highlight them with the goal of practical clinical disposition.


References:

De Carlo T, et al. International Journal of Retina and Vitreous. 2015;doi.org/10.1186/s40942-015-0005-8.

Jackson GR, et al. Invest Ophthalmol Vis Sci. 2014;doi:10.1167/iovs.13-13745.

Owsley C, et al. Ophthalmology. 2016;doi.org/10.1016/j.ophtha.2015.09.041.

Wood A, et al. PLoS One. 2014;doi:10.1371/journal.pone.0096742.

Wu Z, et al. Invest Ophthalmol Vis Sci. 2014;doi:10.1167/iovs.14-14407.


For more information:

Joseph Hallak, OD, PhD, FAAO, is in private practice in Syosset, N.Y. He can be reached at drjhallak@aol.com.


Disclosure: Hallak reports no relevant financial disclosures.