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    Seeing the unseen: why definition matters

    A case study brought to you by the Centre for Eye Health

    Scans of an eye


    A 66-year-old male who reported a history of laser treatment to the right eye described new, sudden onset symptoms of a change in his vision. The symptoms are affecting his depth perception, reading fluency and television clarity. He is a current smoker and is otherwise in good health. He has not seen an ophthalmologist for four years.

    On examination, best-corrected central acuities were counting fingers at 50cm OD and 6/19+2 OS. Amsler grid screening showed visibility of the bottom left corner only OD, and distortion of the whole grid OS. Contrast sensitivity was non-measurable OD and was reduced OS at 1.40 log units using the Mars test (normal range 1.52 to 1.76 log units). Anterior eye examination was unremarkable.

    Dilated fundus examination revealed a large, well-demarcated, fibrotic disciform scar with mixed autofluorescence at the right macula (Figure 1A-1B), a multilayered pigment epithelial detachment, and associated marked disruption of the overlying neurosensory retina, including loss of the ellipsoid zone and external limiting membrane, on spectral domain optical coherence tomography (SD-OCT) (Figure 1C). OCT angiography (Figures 1D-E) revealed a large type 1 neovascular membrane.

    Imaging of the left macula showed an abnormal foveal reflex and a pale appearance of the macula (Figure 2A). Close analysis of the structural OCT B-scans showed sub-retinal fluid at the centre of the macula, and other associated exudative signs. OCT angiography revealed abnormal positive flow signals suspicious of ill-defined choroidal neovascularisation within the PED (Figures 2D-E).

    How soon does this patient need to be referred to an ophthalmologist?

    • a. Within one week
    • b. Within two weeks
    • c. Within one month
    • d. Within six months


    Neovascular AMD in both eyes


    This patient needs to be referred to see his ophthalmologist again a) within one week based on the presence of suspected new neovascular AMD in the left eye, new symptoms of central vision loss and distortion, and macular fluid using imaging.

    Figure 1. Case images from the patient’s right eye. A) Fundus photograph showing a large, sub-foveal, well-demarcated, fibrotic scar and B) corresponding mixed autofluorescence extending beyond the obvious areas of fibrosis on colour photography. C) Central spectral-domain optical coherence tomography (SD-OCT) B-scan showing a multilayered pigment epithelial detachment characterised by three zones: an inhomogenous hyper-reflective band anterior to the RPE, underlying homogeneous hyper-reflective band (two arrows) and prechoroidal cleft (*), with marked loss, disruption and elevation of the overlying neurosensory retina, and degenerative intraretinal cysts (based on the notably, relatively straight border). D) OCT angiography en face projection image and D”) corresponding central flow overlay B-scan image, of the central 10 degree (2.8mm), depicted using the preset avascular slab, and E and E”) toggled using manual slab selection to improve visualisation of the neovascular network.

    Figure 2. Case images from the patient’s left eye. A) Fundus photograph showing abnormal foveal reflex and a pale appearance of the macula. B) Fundus autofluorescence showing mild hypo-autofluorescence centrally with patchy hyper-autofluorescence at the superior macula. C) SD-OCT magnified signs showing sub-retinal fluid, sub-retinal hyper-reflective material, intraretinal hyper-reflective foci and pigment epithelial detachment with mixed internal reflectivity and D) subtle “onion” sign comprising multiple hyper-reflective lines. References images showing the location of the extracted B-scans appears top right in both panels. E and E”) OCT angiography en face projection image of the avascular slab showing an abnormal result, F and F”) manually adjusted to reveal a possible, ill-defined neovascular membrane.

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in the developed world in individuals over 50 years of age.1 Antivascular endothelial growth factor has revolutionised treatment of the condition; however, some patients still experience poor long-term visual outcomes due to the formation of RPE tear, geographic atrophy, and fibrotic disciform scar. The latter, as seen in the case pictured (Figure 1), represents regression of the vascular component of the neovascular membrane and an increase in the fibrous component. Vision varies significantly and can be correlated with OCT.2 3 Overlying loss of the external limiting membrane and ellipsoid zone, irrespective of the scar component is associated with poor visual outcomes.3

    In patients with unilateral neovascular AMD, screening for progression in the fellow eye to neovascular AMD aims to detect signs at an early stage — before irreversible damage to the retinal layers occurs i.e. to prevent central vision loss and vision related disability. Patients with new signs or symptoms suggestive of neovascular AMD should undergo additional imaging.4 5 Frequently, the early signs of a neovascular membrane exhibit no visible fundus lesions and none or minimal autofluorescence abnormality.6 7 Fundus autofluorescence may exhibit hyper-autofluorescence in cases with associated sub-retinal fluid, however in some cases normal autofluourescence can be observed as the RPE and photoreceptor layers remain intact and can remain so for several months after the development of a neovascular membrane.6

    The key signs of neovascular AMD using SD-OCT differ by sub-type; however, exudation is common and can manifest as intraretinal or subretinal fluid, hyper-reflective foci, subretinal hyperreflective material, and/or retinal pigment epithelial detachment.8 Other signs, such as the “onion sign”, prechoroidal cleft, cystoid degeneration or multilayered pigment epithelial detachment noted in the case have also been described and can be helpful for establishing disease prognosis, recurrence, and treatment decisions.9 10

    OCT angiography is an emerging, non-invasive imaging modality that depicts blood flow through the retinal and choroidal vasculatures and can be used to detect macular neovascularisation. Various morphological patterns indicative of clinical activity have been described.11-13 A scheme by Karacorlu13 subdivided choroidal neovascular membranes into three categories: 1) long-filamentous without branching small-capillary networks (dead-tree) associated as in this case with chronicity, inactivity and past treatment, 2) ill-defined lacking distinct membrane morphology patterns (Figure 2) associated with both active and inactive disease, and 3) well-defined with the presence of numerous tiny branching capillaries (medusa or sea-fan) that tend to be clinically active.13 14 Other features beyond shape and branching, such as the presence of anastomoses and loops, vessels termini and a perilesional hypointense halo are also suggestive of disease activity.12

    Patient outcome

    The patient was referred urgently to a medical retinal ophthalmologist to be seen within one week for treatment of the left eye. He was also referred to Guide Dogs NSW/ACT for low vision services.

    What is known on this topic

    • Age-related macular degeneration is characterised by the accumulation of extracellular deposits at the macula including medium to large drusen with or without pigment abnormalities.15
    • Patients who develop an associated neovascular membrane or geographic atrophy are classified as having late AMD.15
    • Early detection of conversion to neovascular late AMD is crucial to ensure timely treatment with an ophthalmologist to optimise visual outcomes.

    What this case illuminates

    • Disciform scars symbolise a disease end point in neovascular late AMD and are associated with debilitating, significant vision loss.3
    • Different imaging modalities have different sensitivity and specificity in detecting early signs of neovascularisation and exudation in AMD. It is vital for clinicians to familiarise themselves with early signs of conversion to neovascular AMD and to utilise multimodal imaging effectively to allow early detection to improve patient outcomes.4 16 17
    • The RANZCO referral pathway for AMD management recommends prompt referral within one week to an ophthalmologist if there is definite or suspected neovascular AMD or referral within two weeks if fluid is detected on imaging in a patient with AMD but no symptoms or clinical signs of neovascular AMD.5

    What evidence gaps remain

    • The COVID-19 pandemic heightens the risk of patients delaying sight-saving treatment and emphasises the importance of patient education on adherence to ongoing care/surveillance in neovascular AMD.18 Further research into how this key health information is best imparted is ongoing.
    • Individuals of lower socioeconomic status or speaking a language other than English at home (approximately 20 per cent) are less likely to receive treatment, implying access issues and a paucity of bulk billing services.19 A greater understanding of the social determinants of health inequity, the subsequent design and implementation of strategies to overcome barriers, is required.
    • Further investigation into health care models to avoid a potentially over-burdened hospital system are required to ensure timely patient access to care.20
    About the Authors

    Amanda Sobbizadeh, BSc, MClin Optom
    Staff Optometrist

    Since graduating from UNSW, Amanda has worked as a rural full-scope optometrist in Upper Hunter region, in nursing homes as an aged care optometrist and also undertaken locum work at several independent and corporate optometry clinics around Sydney. Her areas of interest include dry eye, diabetic retinopathy and glaucoma co-management.

    Dr Angelica Ly, BOptom (Hons), GradCertOcTher, PhD, FAAO
    Lead clinician (Macula), Centre for Eye Health
    Lecturer, UNSW Sydney

    Dr Angelica Ly is a passionate clinician-scientist driven toward applying technology and systems-wide change for better, patient-centred care. She holds leadership positions at the Centre for Eye Health, on the Optometry NSW/ACT board of directors and on the editorial board of the journal Clinical and Experimental Optometry. Her current research interests include advanced retinal image analysis, patient outcomes, and health care delivery.


    The Centre for Eye Health receives primary funding from Guide Dogs NSW/ACT.


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    2. Jaffe GJ, Ying GS, Toth CA, et al. Macular Morphology and Visual Acuity in Year Five of the Comparison of Age-related Macular Degeneration Treatments Trials. Ophthalmology 2019;126(2):252-60.


    4. 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):254-64.

    5. RANZCO. RANZCO Referral Pathway for AMD Management. Australia, 2018.

    6. Ly A, Nivison-Smith L, Assaad N, et al. Fundus Autofluorescence in Age-related Macular Degeneration. Optometry and vision science : official publication of the American Academy of Optometry 2017;94(2):246-59.

    7. Mokwa NF, Ristau T, Keane PA, et al. Grading of Age-Related Macular Degeneration: Comparison between Color Fundus Photography, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography. Journal of ophthalmology 2013;2013:385915-15.

    8. Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. Ophthalmology 2019.

    9. Singh SR, Lupidi M, Mishra SB, et al. Unique optical coherence tomographic features in age-related macular degeneration. Surv Ophthalmol 2020;65(4):451-57.

    10. Kim I, Ryu G, Sagong M. Morphological features and prognostic significance of multilayered pigment epithelium detachment in age-related macular degeneration. 2021:bjophthalmol-2020-318616.

    11. Tew TB, Lai T-T, Hsieh Y-T, et al. Comparison of different morphologies of choroidal neovascularization evaluated by ocular coherence tomography angiography in age-related macular degeneration. 2020;48(7):927-37.


    13. Karacorlu M, Sayman Muslubas I, Arf S, et al. Membrane patterns in eyes with choroidal neovascularization on optical coherence tomography angiography. Eye (Lond) 2019;33(8):1280-89.


    15. Ferris FL, 3rd, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology 2013;120(4):844-51.

    16. Muether PS, Hermann MM, Koch K, et al. Delay between medical indication to anti-VEGF treatment in age-related macular degeneration can result in a loss of visual acuity. Graefes Arch Clin Exp Ophthalmol 2011;249(5):633-7.

    17. Sim PY, Gajree S, Dhillon B, et al. Investigation of time to first presentation and extrahospital factors in the treatment of neovascular age-related macular degeneration: a retrospective cross-sectional study. BMJ Open 2017;7(12):e017771.

    18. Yeter DY, Dursun D, Bozali E, et al. Effects of the COVID-19 pandemic on neovascular age-related macular degeneration and response to delayed Anti-VEGF treatment. Journal francais d’ophtalmologie 2021;44(3):299-306.

    19. Finger RP, Xie J, Fotis K, et al. Disparities in access to anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration. 2017;45(2):143-51.

    20. Gale RP, Mahmood S, Devonport H, et al. Action on neovascular age-related macular degeneration (nAMD): recommendations for management and service provision in the UK hospital eye service. Eye (Lond) 2019;33(Suppl 1):1-21.

    Posted: 26 August 2021

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