Diagnosis and Monitoring of Age-Related Macular Degeneration (AMD)

What is a Diagnosis?

The term diagnosis is defined by the Merriam-Webster Dictionary, as "the art or act of identifying a disease by its signs and symptoms".

In terms of age-related macular degeneration (AMD), that means a health care professional such as an ophthalmologist or optometrist uses a variety of tests and examinations to determine whether a patient may have AMD.² These techniques focus on visual function as well as imaging techniques to visualise the retina and the macula at the back of the eye. Here we introduce you to the different diagnostic techniques related to AMD.

The only way to diagnose age-related macular degeneration (AMD) is to have a thorough eye examination, including a check of the macula, by an optometrist or ophthalmologist.

Note that many of these techniques are also used to monitor a patient over time after they have been diagnosed with age-related macular degeneration. Your healthcare professional will tell you how often you should attend follow up visits, and it is important to follow their advice.

Monitoring your own vision - Amsler Grid

If you have been diagnosed with age-related macular degeneration or are at risk of developing an eye disease, it is important to ensure you are monitoring any changes in your vision.

An Amsler grid is an essential¹ and easy-to-use self-monitoring tool used to detect early changes in your vision. These changes may include distortion (straight lines appearing wavy), blurred patches or dark patches.

It is important not to rely on an Amsler grid for diagnosis, and it is not a substitute for regular eye examinations. The only way to diagnose AMD is to have an eye exam, including a check of the macula, by an optometrist or ophthalmologist. Note that changes in vision on an Amsler grid may also be a sign of another eye disease other than age related macular degeneration.

If you detect any changes in your vision it is important to consult an optometrist or ophthalmologist as soon as possible.

The only way to diagnose age-related macular degeneration is to have a thorough eye examination, including a check of the macula, by an optometrist or ophthalmologist.

In the next section there is an overview of the examinations that may be carried out.

Tests used to diagnose and monitor Age-Related Macular Degeneration (AMD)

Eye examinations performed by optometrists or ophthalmologists.

The only way to diagnose age-related macular degeneration (AMD) is to have a thorough eye examination, including a check of the macula, by an optometrist or ophthalmologist.² In the next section there is an overview of the examinations that may be carried out. Please note that not all tests will be carried out by your health care professional, and the tests used may differ across geographies. If you have any questions related to any of the tests you should ask your health care professional at your next visit.

In general, the more common tests used in the diagnosis and monitoring of AMD are the following:

• Comprehensive eye examination
• Fundus Examination
• Ophthalmoscopy
• Fundus Photography
• Optical Coherence Tomography (OCT)
• Fundus Fluoresceine Angiography
• Fundus Autofluorescence

The less common tests used in the diagnosis and monitoring of AMD are the following:

• Indocyanine Green Angiography
• Microperimetry
• Low-luminance Visual Acuity
• The MNRead Acuity Chart
• Contrast Sensitivity Examination
• The Functional Reading Independence Index

Please refer to the next section for a more detailed description of the tests listed above.

Tests used to diagnose and monitor Age-Related Macular Degeneration (AMD)

Comprehensive Eye Examination

The main symptom people with AMD experience is a loss of vision. Therefore, AMD is often diagnosed by a routine eye exam. A comprehensive visual acuity examination measures a person’s ability to see details, shapes, and letters at a certain distance.³ Best corrected visual acuity (BCVA) is normally assessed using a Snellen Chart but note that alternative charts may also be used by your healthcare professional. The number of letters a person can correctly identify represents his/her visual acuity. Put another way, the further down the Snellen chart a person can read the better their visual acuity is.³

Fundus Examination

The fundus examination is a more in-depth test to help diagnose AMD. It is an optical examination of the retina at the back of the eye. Note that fundus is just a medical term for the part of an organ that is furthest from the opening, and in this case, it refers to the back of the eye. The fundus examination can be conducted using either ophthalmoscopy or fundus photography.² In both methods, dilating drops are applied to the patient's eye to allow the practitioner to see more of the back of the eye.⁴

Ophthalmoscopy

In this eye examination method, the practitioner shines a bright light through the dilated pupil and an ophthalmoscope provides magnified images of the retina. Ophthalmoscopy is an important diagnostic tool for AMD as it allows the practitioner to see retinal abnormalities like atrophy, drusen, pigmentary changes and choroidal neovascularization (CNV).^5,6 There are three forms of ophthalmoscopy.

Direct Ophthalmoscopy

In direct ophthalmoscopy the practitioner shines a bright light through the pupil using a handheld ophthalmoscope.

Indirect Ophthalmoscopy

Indirect ophthalmoscopy is the most common type of ophthalmoscopy.⁵ Here the practitioner sends a bright light through the pupil from a head mounted ophthalmoscope and uses a handheld lens.⁵

Slit-Lamp Ophthalmoscopy

This type of examination is commonly used to diagnose AMD and it is performed with a slit-lamp ophthalmic microscope.⁵ The patient’s chin rests on a slit-lamp device, light is sent through a narrow slit into the patient’s eye and the practitioner examines the fundus through a magnifying glass.⁵

Fundus Photography

Fundus photography is done using a low powered microscope to take colour images of the retina.⁷ It is commonly used in the diagnosis of AMD, as it shows retinal abnormalities like drusen, pigmentary abnormalities, atrophy, bleeding, and fluid buildup.⁷ Images taken over time can be compared to monitor the progress of the disease.

Imaging Modalities and Manifestations

There are a number of imaging techniques that provide a more detailed visualisation of the retina in people with AMD. These techniques allow practitioners to assess the stage and severity of the disease at diagnosis, as well as monitoring the progression of the disease over time.

Optical Coherence Tomography (OCT)

OCT is an important imaging technique for diagnosing and monitoring AMD. It takes cross-section pictures of the retina and provides a detailed evaluation of the health of the retina. OCT can measure retinal thickness, identify drusen and choroidal neovascularisation (CNV), which are typical features of AMD.^8,9

Fundus Fluoresceine Angiography (FFA)

In fluoresceine angiography, an intravenous fluorescent dye is injected intravenously to image retinal blood vessels.¹¹ FFA is typically used to exclude a diagnosis of wet AMD. It can also be used in advanced dry AMD or geographic atrophy as atrophic regions have increased fluorescence due to death of the retinal pigment epithelium (RPE).⁸

FFA images show details of the retinal vasculature, as well as dye elimination in normal parts of the retina and continued fluorescence in areas with retinal abnormalities.¹² 

Fundus Autofluorescence

Fundus autofluorescence is an important imaging technique for diagnosing and monitoring AMD, in particular advanced dry AMD or geographic atrophy (GA).¹¹ A specific light (normally blue) is used to produce autofluorescence of a molecule called lipofuscin, which is typically distributed evenly throughout the retina.⁸ Unhealthy retinal regions may appear darker for atrophic areas, or brighter for drusen which are both signs of AMD.^8,13 The fluorescence pattern can indicate a patient’s potential progression rate of AMD.¹⁴

Indocyanine Green (ICG) Angiography

ICG is is an imaging technique used to exclude wet AMD and also assess atrophic lesions in advanced dry AMD or GA.¹³ The concept of ICG angiography is like fundus autofluorescence. It also uses light that is shot onto the retina to excite fluorescence, though ICG angiography uses an injectable dye in the blood stream and allows a better image resolution.¹³

Additional Functional Tests

In addition to the vision tests outlined above, other functional examinations can be used to monitor visual function in people with AMD and assess the impact on their daily life.

Microperimetry

Microperimetry assesses the capacity of the eye to perceive light stimuli in different parts of the retina. This is a retinal imaging device with a visual field test where the function of photoreceptors can be mapped spatially. Photoreceptors are the light sensitive cells in the retina. In microperimetry, the retina is exposed to small spots of light of various intensities. The patient pressing a button acknowledges the perception of the light stimulus.¹⁵ Possible visual field losses are then identified over a person’s retina.¹⁵

Low-luminance Visual Acuity (LLVA)

The visual acuity of people with AMD is typically reduced in low light conditions.⁸ As the name suggests, low-luminance visual acuity measures visual function in low light conditions. Similar to the Best Corrected Visual Acuity (BCVA), patients view an eye chart, but with LLVA this is done through filters that reduces light levels.¹⁶ The difference between visual acuity measured in bright light (BCVA) and visual acuity measured in low light is calculated and identified as the low luminescence deficit (LLD).¹⁷ A person’s LLD can correlate with AMD lesions.¹⁷ People with early stages of AMD tend to do more poorly on the LLVA examination than the BCVA examination.¹⁷

The MNRead Acuity Chart or Minnesota low vision reading chart

In daily life, a variety of text sizes can be very challenging for people with AMD as they usually develop difficulty with maintaining good reading speed. The MNRead Acuity Chart measures individual’s reading speed as it relates to print size. A person reads sentences in decreasing font sizes aloud from a chart. The point when the reading speed is decreasing with smaller font size corelates with his or her visual ability.

Contrast Sensitivity Examination

The contrast sensitivity examination uses the Pelli-Robson Contrast Sensitivity Chart. This chart uses letters of the same size progressing from high to low contrast.¹⁸ The more difficult it is for a person to distinguish the letters; the lower their contrast sensitivity is scored. In AMD, contrast sensitivity examinations help detect visual abnormalities that might not be captured in a visual acuity exam.¹⁹

The Functional Reading Independence (FRI) Index

The Functional Reading Independence (FRI) Index is a patient-reported measure that assesses the ability of a person with GA to read in a variety of reading-related activities.²⁰

The parameters of the FRI include reading labels on medication bottles or food labels, reading to conduct finances and write checks, and reading words on a television or computer.²⁰ This measure is particularly important for people with advanced dry AMD or GA who can often have visual deficits that are not captured by BCVA.

Helpful resources & links

References:

1. Have AMD? Save Your Sight with an Amsler Grid. Accessed Nov. 15, 2021.
   https://www.aao.org/eye-health/tips-prevention/facts-about-amsler-grid-daily-vision-test
2. Apellis GA Dossier Section 8.3 2.
3. Lakshminarayanan, V. Visual acuity. in Handbook of Visual Display Technology vol. 1 93–99 (Springer Berlin Heidelberg, 2012).
4. Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. The Lancet. 392(10153):1147-59.
5. American Academy of Ophthalmology. What is the difference between direct and indirect ophthalmoscopy? https://www.aao.org/eye-health/ask-ophthalmologist-q/what-is-difference-between-direct-indirect-ophthal. Published September 12, 2016. Accessed August 12, 2020.
6. American Academy of Ophthalmology. What is a Slit Lamp? https://www.aao.org/eye-health/treatments/what-is-slit-lamp Published April 23, 2018. Accessed August 12, 2020.
7. Townsend WD. Scleral depression. Optom Clin. 1992; 2(3);127-44 (1992).
8. Fleckenstein M, Mitchell P, Freund KB. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125:369-90.
9. Garcia-Layana A, Ciuffo G, Zarranz-Ventura J, Alvarez-Vidal A. Optical coherence tomography in age-related macular degeneration. www.amdbook.org. https://amdbook.org/content/optical-coherence-tomography-age-related-macular-degeneration. Updated July 2017. Accessed August 12, 2020.]
10. Boyer DS, Schmidt-Erfurth U, van Lookeren Campagne M, Henry EC, Brittain C. THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET. Retina. 2017 May;37(5):819-835. doi: 10.1097/IAE.0000000000001392. PMID: 27902638; PMCID: PMC5424580.
11. Flaxel CJ, Adelman RA, Bailey ST, et al. AMD preferred practice pattern®. Ophthalmology. 2019.
12. Bennett TJ. Interpretation. Ophthalmic Photographers’ Society website. 2019. Accessed September 9, 2020. https://www.opsweb.org/page/FAinterpretation
13. Holz FG, Sadda SR, Staurenghi G, et al. Imaging protocols in clinical studies in advanced AMD: recommendations from classification of atrophy consensus meetings. Ophthalmology. 2017;124(4):464-78.
14. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al. Progression of geographic atrophy and impact of fundus autofluorescence patterns in AMD. Am J Ophthalmol. 2007;143(3):463-72.
15. Csaky, K. G. et al. Microperimetry for geographic atrophy secondary to AMD. Surv. Ophthalmol. 2019;64, 353-64. 2. Apellis doc. Modules Conent_Modules 6 Conent d3.
16. Sadda SR, Chakravarthy U, Birch DG, Staurenghi G, Henry EC, Brittain C. Clinical endpoints for the study of geographic atrophy secondary to AMD. Retina. 2016;36(10):1806-22.
17. Wu Z, Ayton LN, Luu CD, Guymer RH. Longitudinal changes in microperimetry and low luminance visual acuity in AMD. JAMA Ophthalmol. 2015;133:442–48.
18. Monés J, Rubin GS. Contrast sensitivity as an outcome measure in patients with subfoveal choroidal neovascularisation due to AMD. Eye (Lond). 2005;19(11):1142-50.
19. Sunness JS, Rubin GS, Broman A, Applegate CA, Bressler NM, Hawkins BS. Low luminance visual dysfunction as a predictor of subsequent visual acuity loss from geographic atrophy in AMD. Ophthalmology. 2008 Sep;115(9):1480-8, 1488.e1-2.
20. Kimel M, Leidy NK, Tschosik E, et al. Functional Reading Independence (FRI) Index: a new patient-reported outcome measure for patients with geographic atrophy. Invest Ophthalmol Vis Sci. 2016;57:6298-304.

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