Murat V. Kalayoglu, M.D., Ph.D.
Contributing Editor
Age–related Macular Degeneration (AMD) is the leading cause of blindness in Americans over the age of 55. The pathogenesis of AMD is being elucidated at an accelerating pace, and already key pathogenic mechanisms have been defined to develop novel therapeutics for AMD. These include agents that inhibit the angiogenesis cascade, photodynamic therapy to activate intravenously administered photosensitizers that preferentially accumulate in choroidal neovasculature, and steroid derivatives that inhibit pro – inflammatory molecules in AMD lesions. In contrast to the rapid rate at which AMD therapeutics are being developed, relatively less attention has been given to diagnostics that may aid in identifying patients at risk of developing advanced AMD.
Historically, the Ophthalmologist has relied exclusively on funduscopy to detect progression of AMD. To this day, the 90 diopter slit lamp examination of the macula remains the “bread and butter” of the retinologist. The experienced Ophthalmologist can discern subtle differences over time in patients with AMD, including size and quality of drusen, macular edema through magnified 3D views, and the presence of a choroidal neovascular membrane. In the past, careful documentation and drawings of the AMD macula were essential to ensure optimal management of the patient over time; however, as digital retinal photography continues to develop, sophisticated software is becoming available that can automatically quantify the number, size and shape of drusen.
Such diagnostic advances help quantify existing structural changes in the macula. However, there are relatively fewer advances in tests that measure macular function. Diagnostic tools such as measurement of visual acuity, using the Amsler grid to detect metamorphopsia, and focal ERG have been in use for many years, and overall are inadequate to detect subtle signs that indicate progression of AMD. One recent technological advance – the preferential hyperacuity perimeter (PHP) – may be an exciting addition to the Ophthalmologist’s diagnostic portfolio for AMD.
PHP is a specialized perimeter that applies principles of both static and automated perimetry to detect defects in the visual field. Rather than measuring peripheral visual fields, PHP relies on the concept of hyperacuity to measure subtle differences in the central and paracentral fields. Hyperacuity is defined as the ability to discern a subtle misalignment of an object. Hyperacuity, or Vernier acuity, has a threshold of 3 to 6 seconds of arc in the fovea. Therefore, hyperacuity’s threshold is approximately 10 fold lower than that required for optimal resolution of an object, which is 30 to 60 seconds of arc in the fovea. The brain’s ability to discern such small misalignments is exploited by PHP: hyperacuity stimuli are projected onto the macula, and if the patient’s photoreceptors are perfectly in position from an absence of edema or choroidal neovascularization, then no misalignment is perceived. However, if the patient’s photoreceptors are slightly misaligned due to choroidal neovascularization or from elevation of the retinal pigment epithelium due to drusen, then this misalignment can be perceived by the patient and recorded by the PHP. Thus, if a patient’s AMD has progressed ever so slightly that the visual acuity has not yet changed, PHP may still be able to objectively detect the advancing disease. Another advantage of hyperacuity for measuring macular function is its high resistance to retinal image degradation, allowing diagnostics in patients with cataracts of other causes of opaque media. Furthermore, hyperacuity thresholds of individuals do not tend to show variation with increasing age.
Clinical data support a role for PHP in AMD diagnosis and management. For example, the PHP Research Group recently compared the diagnostic accuracy of the PHP with that of retina specialists relying on funduscopic examination. The researchers studied 64 patients with recent onset CNV and 56 patients with intermediate AMD, and found that retina specialists had a sensitivity of 70%, specificity of 95%, and an overall accuracy of 0.82 in detecting recent onset CNV. In comparison, PHP had a sensitivity of 83%, specificity of 87%, and overall accuracy of 0.85 in detecting the same lesions. The authors concluded that the overall accuracy of the PHP was as good as a retina specialist’s review of stereo color photographs, and that PHP could serve as a good “gatekeeper” for patients at risk of developing CNV. While the clinical acumen and experience of an expert Ophthalmologist will always be necessary to make optimal management decisions through biomicroscopy, PHP may serve as a useful adjunct in facilitating diagnosis and instituting appropriate therapeutics in patients with AMD.