Current evidence revealing visual impairment in early/intermediate age-related macular degeneration (AMD) poses the clinical dilemma of whether it’s appropriate to perform visual field testing on patients.
Visual impairment is well established in late AMD, but what about in the earlier stages?
Studies have revealed visual impairment in early/intermediate AMD, such as reduced visual acuity and contrast sensitivity.1-3 Recently, a systematic review highlighted that significant functional defects in early/ intermediate AMD eyes can also be detected via visual field testing.4 But does this mean we should perform visual fields for patients with early/intermediate AMD?
Ultimately, potential patient benefit should be the reason we decide to include a clinical test or not
Current Functional Tests for AMD
AMD is a leading cause of irreversible blindness in developed countries, affecting approximately one in seven Australians over 50-years-old.
Optometrists are at the clinical forefront of early AMD detection and with the growing routine use of technologies, such as optical coherence tomography, are well equipped to detect disease changes which signal progression towards severe, irreversible blindness. This clinical practise is led by various guidelines that instruct clinical observation of retinal structural changes associated with AMD progression: drusen, pigmentary changes, outer retinal atrophy, and neovascularisation via traditional and advanced ocular imaging technologies.5-7
The assessment of retinal functional changes associated with AMD progression, however, is less clear. As such, current clinical functional testing for AMD is mostly limited to visual acuity and the Amsler grid. These tests are problematic as visual acuity measures foveal high-contrast acuity, despite the fact that initial AMD insult manifests para-centrally and at lower light levels,8,9 while the Amsler grid demonstrates poor sensitivity.10
Measuring Retinal Function in the Early Stages of AMD
Retinal functional changes in eyes with early/intermediate AMD have been previously measured by researchers employing a variety of clinical examinations, including visual acuity, the Amsler grid, contrast sensitivity, adaptation, colour vision, perimetry, multifocal electroretinography, reading speed and temporal function.1-3,11-13 These functional changes have been linked to retinal structural changes and disease progression,2,13 and they may even predict AMD development before any structural changes are clinically detectable.14 Cumulatively, the evidence suggests that the functional status of AMD patients may be of clinical relevance. However, many of these tests are not clinically accessible nor practical due to the need for specialised equipment.
CAN VISUAL FIELD TESTING PROVIDE THE ANSWER?
Visual fields are a fundamental part of clinical practice, providing invaluable location specific visual functional data, which is key to the diagnosis and monitoring of many other retina-involving diseases, such as optic neuropathies and retinal dystrophies. Despite many studies that suggest visual fields may also be affected in early/ intermediate AMD, the lack of evidence synthesis precludes consideration of clinical visual field testing in AMD patients.
Recently, the research team at the Centre for Eye Health and the UNSW School of Optometry and Vision Science decided to tackle this issue by systematically reviewing the literature to address the question: should visual fields be considered for routine functional assessment of early/ intermediate AMD?4
The team reviewed all studies that used commercially accessible visual field devices and protocol to assess early/intermediate AMD, including standard automated perimetry (SAP) white-on-white; flicker perimetry; and frequency-doubling technology. A total of 26 studies were appraised and meta-analysis conducted where possible.
The team reported consistent changes in global visual field indices, including decreased mean deviation (MD), increased pattern standard deviation (PSD), and decreased mean sensitivity (MS) in eyes with early and/or intermediate AMD versus normal eyes. Specifically, metaanalysis found a statistically significant reduction of −1.52dB for MD and −1.47dB for MS using SAP under photopic (standard lighting) in early and/or intermediate AMD versus normal eyes.4
THE ROLE OF CLINICAL RELEVANCE
Despite statistically significant visual field defects using SAP for early/intermediate AMD eyes, the values were smaller than SAP test-retest variability (Å}2.5dB for MD, Å}2dB for MS) and hence not clinically relevant. There was also very limited evidence linking visual field outcomes to real-world patient outcomes, i.e., does knowledge of a visual field defect in patients with early/ intermediate AMD improve vision-related quality of life for the patient? Ultimately, potential patient benefit should be the reason we decide to include a clinical test or not, regardless of the test’s accuracy.15 Thus, current evidence suggests that the commercially accessible SAP is unlikely to be clinically relevant for patients with early/intermediate AMD.
THE FUTURE FOR VISUAL FIELD TESTING IN AMD
This is not yet the end of the story, however. A number of research groups have turned their focus to alternative visual field testing protocols, beyond SAP, that probe specific pathophysiological mechanisms in AMD. In particular, visual field testing at lower light levels is being explored based on evidence that initial AMD insult manifests as rod photoreceptor disruption.14,16,17
Our research group is also exploring alternate stimulus sizes which can reveal greater visual field defects in AMD,18 in line with other work on optic nerve disease that has produced similar results in these conditions.19-21 This is due to the inability of the standard Goldmann III (GIII) stimulus size to completely summate retinal sensitivity, thus potentially ‘missing’ visual field defects. The case study (Figure 1) demonstrates an intermediate AMD eye that has been assessed using SAP 10-2 with GIII, GII, and GI stimulus sizes. Note that when using the GII and GI stimulus sizes, which operate within complete spatial summation, much greater visual field defects are revealed compared to GIII.
Thus, while the commercially accessible SAP is unlikely to be clinically relevant for patients with early/intermediate AMD, several other alternative visual field testing devices and/or protocols, which exploit the pathophysiological mechanisms of AMD, are still being explored and may yet become part of future clinical practice.
Dr Lisa Nivison-Smith BSc (Hons), PhD, FAAO, is currently an NHMRC Research fellow and Scientia Lecturer at the Centre for Eye Health and the School of Optometry and Vision Science at the University of New South Wales. She did her undergraduate degree in molecular biology and genetics at the University of Sydney in 2006 and then continued to a PhD in tissue engineering, making a synthetic blood vessel model for testing of therapeutics in vitro. She finished her PhD in 2011 and moved fields again, starting in the field of vision science at the University of New South Wales. She helped establish the Retinal Networks Laboratory with Michael Kalloniatis and then the research group at the Centre for Eye Health. Dr Nivison-Smith’s current research interests lie in retinal disease biology, particularly photoreceptor degenerations such as age-related macular degeneration and retinitis pigmentosa.
Matt Trinh BSc (Hons), BOptom, MOptom, graduated in 2014 from UNSW, and has since made Newcastle his home. He has a keen interest in research, particularly investigating new technologies in relation to non-exudative agerelated macular degeneration. A PhD candidate at Centre for Eye Health, his research is titled, Gauging local ocular manifestations in nonexudative age-related macular degeneration, as defined by OCT, OCTA, and Microperimetry.
- Lott LA, Schneck ME, Haegerstrom-Portnoy G, et al. Simple Vision Function Tests that Distinguish Eyes with Early to Intermediate Age-related Macular Degeneration. Ophthalmic Epidemiol. 2021;28(2):93-104. doi:10.1080/09 286586.2020.1793371
- Chandramohan A, Stinnett SS, Petrowski JT, et al. Visual function measures in early and intermediate age-related macular degeneration. Retina Phila Pa. 2016;36(5):1021- 1031. doi:10.1097/IAE.0000000000001002
- Pondorfer SG, Wintergerst MWM, Gorgi Zadeh S, et al. Association of Visual Function Measures with Drusen Volume in Early Stages of Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2020;61(3):55. doi:10.1167/iovs.61.3.55
- Trinh M, Kalloniatis M, Nivison-Smith L. Should Clinical Automated Perimetry Be Considered for Routine Functional Assessment of Early/Intermediate Age-Related Macular Degeneration (AMD)? A Systematic Review of Current Literature. Ophthalmic Physiol Opt J Br Coll Ophthalmic Opt Optom. 2022;42(1):161-177. doi:10.1111/opo.12919
- AAO PPP Retina/Vitreous Committee HC for QEC. Age- Related Macular Degeneration PPP 2019. Published online October 11, 2019. Accessed January 4, 2022. https://www. aao.org/preferred-practice-pattern/age-related-maculardegeneration- ppp
- Hart K, Ayton L, Abbott C, et al. 2019 Clinical Practice Guide for the diagnosis, treatment and management of Age-Related Macular Degeneration. Published online February 8, 2019. https://www.optometry.org.au/wpcontent/ uploads/Professional_support/Practice_notes/ AMD-Clinical-Practice-Guide-2019_final_designed_v5.pdf
- Hart KM, Abbott C, Ly A, et al. Optometry Australia’s chairside reference for the diagnosis and management of age-related macular degeneration. Clin Exp Optom. 2020;103(3):254-264. doi:10.1111/cxo.12964
- Owsley C, Jackson GR, Cideciyan AV, et al. Psychophysical evidence for rod vulnerability in agerelated macular degeneration. Invest Ophthalmol Vis Sci. 2000;41(1):267-273.
- Curcio CA, Medeiros NE, Millican CL. Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1996;37(7):1236-1249.
- Crossland M, Rubin G. The Amsler chart: absence of evidence is not evidence of absence. Br J Ophthalmol. 2007;91(3):391-393. doi:10.1136/bjo.2006.095315
- Wu Z, Ayton LN, Guymer RH, Luu CD. Comparison Between Multifocal Electroretinography and Microperimetry in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2014;55(10):6431-6439. doi:10.1167/iovs.14-14407
- Parisi V, Perillo L, Tedeschi M, et al. Macular function in eyes with early age-related macular degeneration with or without contralateral late age-related macular degeneration. Retina Phila Pa. 2007;27(7):879-890. doi:10.1097/IAE.0b013e318042d6aa
- Neelam K, Nolan J, Chakravarthy U, Beatty S. Psychophysical Function in Age-related Maculopathy. Surv Ophthalmol. 2009;54(2):167-210. doi:10.1016/j. survophthal.2008.12.003
- Owsley C, McGwin G, Clark ME, et al. Delayed Rod- Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration. Ophthalmology. 2016;123(2):344-351. doi:10.1016/j. ophtha.2015.09.041
- Schünemann HJ, Mustafa RA, Brozek J, et al. GRADE guidelines: 22. The GRADE approach for tests and strategies-from test accuracy to patient-important outcomes and recommendations. J Clin Epidemiol. 2019;111:69-82. doi:10.1016/j.jclinepi.2019.02.003
- Steinberg JS, Fitzke FW, Fimmers R, Fleckenstein M, Holz FG, Schmitz-Valckenberg S. Scotopic and Photopic Microperimetry in Patients With Reticular Drusen and Age-Related Macular Degeneration. JAMA Ophthalmol. 2015;133(6):690-697. doi:10.1001/ jamaophthalmol.2015.0477
- Cassels NK, Wild JM, Margrain TH, Chong V, Acton JH. The use of microperimetry in assessing visual function in age-related macular degeneration. Surv Ophthalmol. 2018;63(1):40-55. doi:10.1016/j.survophthal.2017.05.007
- Choi AYJ, Nivison-Smith L, Phu J, et al. Contrast sensitivity isocontours of the central visual field. Sci Rep. 2019;9(1):1-14. doi:10.1038/s41598-019-48026-2
- Kalloniatis M, Khuu SK. Equating spatial summation in visual field testing reveals greater loss in optic nerve disease. Ophthalmic Physiol Opt J Br Coll Ophthalmic Opt Optom. 2016;36(4):439-452. doi:10.1111/opo.12295
- Phu J, Khuu SK, Bui BV, Kalloniatis M. A Method Using Goldmann Stimulus Sizes I to V-Measured Sensitivities to Predict Lead Time Gained to Visual Field Defect Detection in Early Glaucoma. Transl Vis Sci Technol. 2018;7(3):17. doi:10.1167/tvst.7.3.17
- Antwi-Boasiako K, Carter-Dawson L, Harwerth R, Gondo M, Patel N. The Relationship Between Macula Retinal Ganglion Cell Density and Visual Function in the Nonhuman Primate. Invest Ophthalmol Vis Sci. 2021;62(1):5. doi:10.1167/iovs.62.1.5