Shifting demographics of the American population, due to the “Silver Tsunami,” mean an increased prevalence of age-related eye diseases, such as AMD.1 Thus, to provide the best care to our patients, we, as eye care providers, should be on the cutting edge of the early detection and management of such ocular conditions. Improved understanding of the pathogenesis of exudative (wet) AMD has lead to the development of treatment options to prevent and preserve long-term vision. Early detection of structural and functional changes in patients with non-exudative (dry) AMD are key to identify to address modifiable risk factors with the goal of slowing or preventing progression to late-stage forms of AMD (See “Managing AMD,” p.21).
While diagnostic technology cannot replace stereoscopic biomicroscopy and ancillary testing — including structural and functional testing in AMD — it does aid in the early identification of non-exudative and exudative AMD, helping us to determine the best course of action for these patients, management-wise.
Here’s a look at the diagnostic devices that aid in the diagnosis and/or management of AMD:
For those in whom drusen has been identified, fundus photography aids in documenting the progression of AMD. There are two main types of fundus photography: (1) traditional, which captures roughly 50° of the retina, and (2) ultra-widefield imaging, which uses scanning laser ophthalmoscopy to create pseudo-color or true color images and captures up to 200° of the retina. Traditional fundus photography, while capturing a smaller field of view in individual photographs, enables the user to create a montage of images to visualize a wide retinal field. Ultra-widefield and traditional fundus photography systems may incorporate autofluorescence (FAF) and fluorescein angiography into a single device.2 Documentation of mid-peripheral and peripheral retinal findings in AMD, including extra-macular retinal pigment epithelium changes (RPE) and drusen, may lead to improved understanding of the complex pathogenesis and prognosis of AMD.2
MACULAR PIGMENT OPTICAL DENSITY (MPOD)
MPOD is a measure of the ability of lutein and zeaxanthin to absorb blue light, and can be used as a biomarker of a patient’s carotenoid levels.3 As concluded by the AREDS2 investigators, increased levels of zeaxanthin and lutein reduce the risk of progression of intermediate stage non-exudative AMD.1 As a known modifiable risk factor for the development and progression of AMD, early identification of low MPOD allows for early intervention, which may include diet and lifestyle changes and nutritional supplementation to increase zeaxanthin and lutein levels.3
Common concerns of older adult patients with and without early non-exudative AMD include difficulty while driving at night and difficulty adjusting to sudden changes in room illumination.4 Dark adaptation abnormality is an early detectable change in older adults prior to decreases in VA, which is associated with increased risk of early non-exudative AMD three years after detection.4 Measurement of dark adaptation and abnormal rod function, measured on commercially available systems, may be a useful adjunct for patients who may be at greater AMD risk, with considerations for patient counseling and monitoring.
FUNDUS AUTOFLUORESCENCE (FAF)
FAF technology employs a confocal scanning laser or fundus camera to selectively discern fluorophores (including lipofuscin) within the retina. Specifically, this technology uses a particular excitation wavelength ranging from blue (488 nm) to near infrared (790 nm) to detect the presence of lipofuscin in conditions like AMD.5,6 Lipofuscin is a biomarker of oxidative damage and has a pro-inflammatory effect in the retina, which contributes to the underlying pathogenesis of AMD progression.1 Detection of reticular pseudo-drusen, an important risk factor for the development of late-stage AMD, is also possible with FAF.1
In addition, the technology can aid in the detection and monitoring of geographic atrophy (GA)-induced atrophic lesions seen in late-stage AMD.6
OPTICAL COHERENCE TOMOGRAPHY (OCT)
SD-OCT, or spectral-domain optical coherence tomography, is a non-invasive imaging modality that employs light waves to acquire cross-sectional images of the retinal layers. It is becoming the standard of care in the diagnosis of patients with AMD, as it is the primary ancillary test that complements our clinical examination and helps us to form the basis of patient management.1 SD-OCT has been the driving force behind recent advancements, including swept-source OCT, or SS-OCTA, and OCT angiography, or OCTA.
SD-OCT is central to the monitoring of non-exudative AMD, as it can show hyper-reflective foci, reticular pseudo-drusen, pigment abnormality and drusenoid pigment epithelial detachment, helping to determine a patient’s risk for progression to late-stage AMD — either GA or the development of a choroidal neovascularization (CNV).1,7 In CNV, namely, type 1 neovascularization, for example, a low-lying fibrovascular pigment epithelial detachment may appear on B-scan, which highlights the space between the RPE and Bruch’s membrane where the CNV resides, producing what is known as a “double layer sign.”8 Presence of a CNV can then be confirmed with fluorescein angiography or OCTA.8
While we often rely on traditional B-scan images of OCT for the monitoring of disease progression, analysis of en-face imaging can be a very useful adjunct. Specifically, an en-face image is a coronal — rather than cross-sectional — view of the retina. Manual control enables you to segment slabs of specific thickness from superficial retina through to the choriocapillaris to aid in the localization of pathology, including differentiation of drusen, which lies below the RPE, and reticular pseudo-drusen, which are located internal to the RPE. En-face OCT can also act as a form of surrogate of true FAF, as a way to monitor GA lesions.9
SS-OCTA. This device uses a longer wavelength (typically 1050 nm) as compared to SD systems, and has the ability to perform up to 100,000 A-scans per second. The result is a high-resolution image with improved ability to image fine choroidal and sub-RPE detail.10 (Topcon Medical Systems recently received FDA clearance for its DRI OCT Triton, featuring SS-OCT.)
OCTA. A non-invasive method of imaging retinal and choroidal vasculature, the OCTA concept is based on knowledge that within a short (i.e. millisecond) time, the only movement in the retina stems from the movement of red blood cells.10 Multiple B-scans are taken at the same location at a specified time interval; when the scans are compared and a decorrelation signal is produced, the result is a map of moving red blood cells in the retina and choroid.10 If CNV is present, the red blood cells circulating through the neovascular lesion will be visible at the level of the choriocapillaris or outer retina, defining the structural boundaries of the lesion.
While exudative AMD is traditionally defined by the presence of exudation of the blood vessels, detected through clinical examination or leakage on fluorescein angiography, subclinical neovascularization, present between Bruch’s membrane and the RPE, can be identified via OCTA in up to 15% of patients who have intermediate stage non-exudative AMD, termed neovascular dry AMD.10 These patients are more likely to develop clinical exudative AMD, resulting in significant VA decline, as compared with patients without subclinical neovascularization, and, as such, are important to identify early to preserve long-term VA.10
Microperimetry allows for the analysis of a fine central VF defect and measurement of stability of fixation, which relates to the underlying retinal structure in AMD patients. Specifically, the technology provides a precise measurement of retinal sensitivity, including measurement in mesopic or scotopic light levels that can enable the detection of early functional change in non-exudative, or dry, AMD.11 Microperimetry results are often also combined with structural analysis, via OCT or through fundoscopic appearance to present a more complete picture of the structural photoreceptor damage and resultant fine central visual damage, which occurs in early AMD, prior to significant VA change.11 Subtle fixation instability, detectable by microperimetry, can indicate loss of reading ability in patients with AMD. This may lead to low-vision rehabilitation strategies.11
Two types of angiography are employed for AMD: (1) fluorescein angiography and (2) indocyanine green angiography.
Flourescein angiography is considered the gold standard in the detection of new CNV in exudative AMD, as it enables the practitioner to discern dynamic changes, including leakage, pooling and staining patterns.1 While it may be used to aid in or confirm the initial diagnosis of CNV, SD-OCT is the preferred method for monitoring exudative AMD, determining effect of treatment and interval of treatment, namely anti-VEGF therapy, due to its noninvasive nature and ability to detect subretinal fluid and structural changes with high resolution.1,12
Indocyanine green has a fairly narrow role in the management of AMD, but may be used adjunctively with fluorescein angiography to identify CNV in AMD, or to identify the presence of aneurysmal neovascularization of choroidal vessels in polypoidal choroidal vasculopathy.8 Further, due to the longer wavelength of light that indocyanine green absorbs and emits, it can be used for visualization of choroidal vasculature in the presence of intraretinal blood, pigment and exudate.1,8
Retinal imaging using adaptive optics involves a measurement of aberrations using a Hartman-Shack wavefront sensor and compensation for wavefront error driven by software algorithms, which process and control a deformable mirror.13
Though not yet commercially available in the United States, adaptive optics could prove useful in imaging photoreceptors with high resolution to detect very early structural retinal change in AMD.
The realm of retinal diagnostics is advancing rapidly and has allowed for the continued evolution of our understanding of retinal, choroidal and optic nerve disease pathophysiology. General imaging trends include wider fields of view and faster scanning speeds to ultimately improve image resolution. As clinicians, even with advanced technology, we must remember that the limiting factor in diagnosis is the interpreting doctor, and understand the limitations of normative databases and automated segmentation. With the early identification and response to clinical change in AMD patients, including the identification of structural and functional change, appropriate management and timely referrals can be made with the goal to preserve long-term vision. OM
- Age-Related Macular Degeneration Preferred Practice Pattern – Updated 2015. American Academy of Ophthalmology website. https://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015 Updated Jan. 2015. Accessed March 12, 2018.
- Oellers P, Lains I, Mach S, et al. Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration. Clinical Ophthalmology. 2017;11:1967-74.
- Davey PG, Alvarez SD, Lee JY. Macular pigment optical density: repeatability, intereye correlation, and effect of ocular dominance. Clinical Ophthalmology. 2016;10:1671-78.
- Owsley C, McGwin G, Cleark ME, Jackson Gr, et al. Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration. Ophthalmology. 2016;123: 344-51.
- Delori FC, Dorey CK, Staurenghi G, Arend O, et al. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Investigative Ophthalmology & Vision Science. 1995; 36: 718–29.
- Schmitz-Valckenberg S, Fleckenstein M, Gobel AP, Sehmi K, et al. Evaluation of autofluorescence imaging with the scanner laser ophthalmoscope and the fundus camera in age-related geographic atrophy. American Journal of Ophthalmology. 2008;146:183-92.
- Roberts PK, Baumann B, Schlanitz FG, Sacu S, et al. Retinal pigment epithelial features indicative of neovascular progression in age-related macular degeneration. British Journal of Ophthalmology. 2017;101:1361-66.
- Dansingani KK, Gal-Or O, Sadda SR, Yanuzzi LA, et al. Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesion in the taxonomy of ‘expanded spectra’-a review. Clinical & Experimental Ophthalmology. 2018; 46: 189-200.
- Schmitz-Valckenberg S, Sahel JA, Danis R, Fleckenstein M, et al. Natural history of geographic atrophy progression secondary to age-related macular degeneration (Geographic Atrophy Progression Study). Ophthalmology. 2016; 123: 361-68.
- De Oliveira Dias JR, Zhang Q, Garcia JMB, et al. Natural history of subclinical neovascularization in nonexudative age-related macular degeneration using swept-source OCT angiography. Ophthalmology. 2018;125:255-266.
- Midena E, Pilotto E. Microperimetry in age: related macular degeneration. Eye (Lond). 2017; 31: 985-94.
- Gao SS, Jia Y, Zhang M, et al. optical coherence tomography angiography. Investigative Ophthalmology & Vision Sciences. 2016; 57: 27-36.
- Zhang B, Li N, Kang J, He Y, et al. Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update. International Journal of Ophthalmology. 2017; 10: 1751-58.