Sample OCT scan showing choroidal hypertransmission

Importance of recognizing and referring GA

Because GA progression is relentless and irreversible, early detection and referral is critical. Age-related macular degeneration (AMD), which can progress to GA, often remains undiagnosed, which can create a barrier for patients to receive proper care.1-4


Out of 201 eyes, 75 eyes were coded as early or intermediate AMD5*

But when using the Hoover categorization

did not have GA

47%

(n=35/75)

had GA

53%

(n=40/75)


*In a recent, retrospective study of patients (n=201 eyes) with AMD referred to a single low vision rehabilitation center from October 2018 to June 2022, GA was diagnosed for the study using microperimetry with infrared imaging (dense scotoma) or complete GA on OCT imaging.5



Patient coding may not provide adequate information about GA prevalence, which may be due to5:

  • Inadequate attention paid to coding GA (untreatable at the time)
  • Good visual acuity may lead to an underdiagnosis of GA

Limitations of the study include5:

  • GA coded as stage 3 or 4 was aggregated into 1 category; within the context of the retrospective study, it was difficult to distinguish the 2 levels when microperimetry and infrared imaging are used as the basis for determining the level to code
  • The number of patients and eyes included is small, and as such, these findings may not reflect the true rate of underreporting

Identify GA in the Cross-section

GA may not be visible on every OCT B-scan—careful selection of the cross-section using the reference image is critical for correctly identifying signs of atrophy.6

Identify and monitor GA through multimodal imaging

GA is characterized by atrophic lesions with sharply defined borders due to cell layer loss, and can be distinguished from other forms of AMD via imaging. There are different imaging modalities that can detect GA. Click on the imaging modalities below to see how the different signs characteristic of GA can be presented.7

Optical Coherence Tomography (OCT) B-scan

Healthy OCT B-scan

© 2022. This work is licensed under a CC BY 4.0 license. “Automatic detection of age-related macular degeneration based on deep learning and local outlier factor algorithm”, "Figure 5A", He T, Zhou Q, Zou Y. Diagnostics (Basl).

Abnormal OCT B-scan Image 1

Reproduced from "Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression," Thiele S, Nadal J, Pfau M, et al, 2021;105(2):239-245, with permission from BMJ Publishing Group Ltd.

Drusen8

Choroidal hypertransmission8

Loss of RPE and photoreceptor layers8,9

Collapse of PED leading to atrophy as shown by hypertransmission8,9

Abnormal OCT B-scan Image 2

Image courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.

Hypertransmission seen in GA7

Loss of photoreceptor as well as RPE and choriocapillaris layer7

Images may vary based on different device manufacturers and imaging platforms.

What to look for:

  • Drusenoid PED, hyper-reflective foci, and reticular pseudodrusen are indicative of areas at high risk for developing atrophy7
  • Loss of photoreceptor as well as RPE and choriocapillaris layer7
  • Increase in choroidal hypertransmission indicative of atrophy7
  • Drusen collapse is a precursor to atrophy8

Considerations:

  • Cross-section needed for accurate recognition10
  • Can provide early GA diagnosis11
  • Scans are in high resolution11
  • Challenges in image interpretation can lead to longer reading times12

Optical Coherence Tomography (OCT) en face and Near Infrared Reflectance (NIR)

If you do not have access to FAF imaging, OCT en face can be used as a substitute to visualize the full extent of GA lesions. On certain machines, NIR images can be acquired simultaneously with OCT en face images. Using both OCT en face and NIR scans allows for the highest accuracy in detecting RPE indicative of GA.7,13

Healthy OCT en face Image*

Image courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.

OCT en face Image 1

© 2019. This work is licensed under a CC BY 4.0 license. “Choriocapillaris flow impairment surrounding geographic atrophy correlates with disease progression”, "Figure 5D", Nassisi M, Baghdasaryan E, Borrelli E, et al. PLoS One.

Multifocal lesion appears as a bright area due to increased penetration of light into the choroid caused by RPE and outer retina atrophy14

 

OCT en face Image 2

© 2019. This work is licensed under a CC BY 4.0 license. “Choriocapillaris flow impairment surrounding geographic atrophy correlates with disease progression”, "Figure 5E", Nassisi M, Baghdasaryan E, Borrelli E, et al. PLoS One.

Progression of larger multifocal lesion with subfoveal involvement14

Healthy NIR Image

© 2021. This work is licensed under a CC BY 4.0 license. "Fundus autofluorescence and clinical applications", "Figure 2E", Pole C, Ameri H. JOVR [Internet].

NIR Image 1

Image courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.

Characteristic C-shaped lesion without subfoveal involvement15

NIR Image 2

Image courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.

Progression of lesion without subfoveal involvement15

Images may vary based on different device manufacturers and imaging platforms.

What to look for:

  • Distinct borders, location, and size of lesion7,13
  • Lesions appear hyperreflective on NIR and OCT en face images vs hyporeflective on FAF images7,13

Considerations:

  • Allows for more comprehensive visualization of GA lesion borders in the absence of FAF7,10,12
  • OCT en face images can guide you in selecting the proper cross-section for OCT B-scans6,7
  • Interpretation dependent on imaging quality7

Fundus Autofluorescence (FAF)

Healthy FAF Image

© 2021. This work is licensed under a CC BY 4.0 license. “Fundus autofluorescence and clinical applications”, "Figure 2B", Pole C, Ameri H. JOVR [Internet].

FAF Image 1

© 2021. This work is licensed under a CC BY 4.0 license. “Fundus autofluorescence and clinical applications”, "Figure 4", Pole C, Ameri H. J Ophthalmic Vis Res.

Areas of hypoautofluorescence showing multifocal lesion without subfoveal involvement7

Hyperautofluorescence indicating areas at high risk for atrophy7

FAF Image 2

Image courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.

Hypoautofluorescence15

Hyperautofluorescence15

FAF Image 3

Image courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.

Hypoautofluorescence15

Hyperautofluorescence15

Images may vary based on different device manufacturers and imaging platforms.

What to look for:

  • Depigmented, hypoautofluorescence in areas with atrophy7,16
  • Abnormal hyperautofluorescent border that show areas of ongoing RPE cell dysfunction7,16
    • A hyperfluorescent border is predictive of atrophic progression
    • Hyperfluorescence indicates areas at high risk for atrophy

Considerations:

  • Commonly used to assess both lesion size and the progression rate of GA12,17
  • Several risk factors associated with a higher GA progression rate can be seen on FAF, such as better visualization of7,12,17:
    • Lesion size
    • Focality of multifocal lesions
    • Location without subfoveal involvement
    • Pattern (eg, diffuse and banded)
  • High contrast imaging makes the atrophy easier to detect12
  • Can be challenging to identify atrophy in the fovea12

Color Fundus Photography (CFP)

Healthy CFP Image

© 2016. This work is licensed under a CC BY 4.0 license. “Infrared reflectance imaging in age-related macular degeneration”, "Figure 1A", Ly A, Nivison-Smith L, Assaad N, Kalloniatis M. Ophthalmic Physiol Opt.

CFP Image 1

© 2012 Karger Publishers, Basel, Switzerland.

Area of atrophy8

CFP Image 2

Reproduced from "Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression," Thiele S, Nadal J, Pfau M, et al, 2021;105(2):239-245, with permission from BMJ Publishing Group Ltd.

Area indicative of atrophy8

Choroidal vasculature8

CFP Image 3

Reproduced from "Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression," Thiele S, Nadal J, Pfau M, et al, 2021;105(2):239-245, with permission from BMJ Publishing Group Ltd.

Area of atrophy8

Images may vary based on different device manufacturers and imaging platforms.

What to look for:

  • Visible choroidal vasculature7
  • Areas of hypopigmentation with sharply demarcated borders7

Considerations:

  • Detects wide range of abnormalities12
  • Difficult to detect subtle changes7
  • CFP may show abnormalities that present similarly to GA, but are not GA. It is important to use multimodal imaging and a holistic assessment to properly diagnose7,12,18
  • Limited ability to assess full extent of lesion progression (may underestimate the size of the lesion)7,18
  • May not exhibit many lesion characteristics associated with disease progression due to reduced contrast7,12

CFP=color fundus photography; FAF=fundus autofluorescence; INL=inner nuclear layer; NIR=near infrared reflectance; OCT=optical coherence tomography; PED=pigment epithelial detachment; RPE=retinal pigment epithelium.

There are several factors that can increase the rate of GA progression7

It’s important to refer any patients who are exhibiting signs of GA, whether they have a higher or lower risk of developing GA.


Images may vary based on different device manufacturers and imaging platforms.

Reprinted from Ophthalmology, 125(3), Fleckenstein M, Mitchel P, Freund KB, et al. “The progression of geographic atrophy secondary to age-related macular degeneration”, 369-390, 2018, with permission from Elsevier.

Recognize GA and how it progresses in different patients

Multimodal imaging can clearly show the progression of Geographic Atrophy (GA)7

75-year-old woman

Hypothetical patient

Medical history:

  • No family history of AMD
  • BMI 39
  • History of stroke, hypertension, and hyperlipidemia

Baseline

  • BCVA OD: 20/25
  • BCVA OS: 20/20
  • Despite atrophy, BCVA is still relatively unaffected due to foveal sparing
  • Failed a DMV driving test
  • Visual function: Patient reports distorted vision

NIR and OCT B-scan

Despite significant atrophy, the fovea is still partially intact

Hypertransmission defect outside the fovea; subsidence of OPL and INL can be seen around the area of atrophy

CFP

2 Years After (2020)

  • OD: 20/100
  • OS: 20/25
  • Visual function: Reports seeing horizontal lines in inferior field while watching television OD

OCT B-scan and en face

Complete RPE and outer retinal atrophy (cRORA) parafoveally

cRORA with choroidal hypertransmission defect. Visual acuity is still somewhat preserved due to partial foveal sparing

CFP

Images are courtesy of Dr Julie Rodman at the Broward Eye Care Institute.

OCT and FAF can provide better visualization of Geographic Atrophy (GA) than CFP7,11,12

71-year-old man

Hypothetical patient

Medical history:

  • Current smoker (40 years); smokes 1 pack/day
  • BMI 37
  • Family history of AMD
  • BCVA OD: 20/30
  • Patient at baseline has RPE mottling, drusen, and parafoveal patches of atrophy with minimal foveal involvement on CFP OD
  • Visual function: Patient reports decreased vision, particularly at night, and “pinhole-like” black spots in his center vision

CFP

Shows some area of GA

GA is less apparent

OCT B-scan

Complete RPE and outer retinal atrophy (cRORA) with increased hypertransmission into choroid

FAF

Lesion without subfoveal involvement; hyperfluorescent border around the GA lesions indicating areas that are at risk for further progression

  • GA is apparent in both OCT and FAF images
  • On OCT, there is the presence of hypertransmission and an area of complete atrophy
  • CFP does not show the full extent of GA, and the severity of the disease can be underestimated when only using CFP

Images are courtesy of Dr Julie Rodman at the Broward Eye Care Institute.

Geographic Atrophy (GA): Visual acuity is poorly correlated to lesion size19,20

  • Change in visual acuity (VA) may not fully capture disease progression19,20
  • Visual function continues to decline as lesions grow18,20,21

80-year-old woman

Hypothetical patient

Medical history:

  • No family history of AMD
  • BMI 28
  • Nonsmoker with exposure to secondhand smoke
  • Diabetes, hypertension
  • A large area of GA is present at baseline examination. However, BCVA is relatively unaffected due to foveal sparing
  • Within 4 years, OS GA has progressed, but BCVA has only declined slightly as fovea is still intact

Baseline

  • BCVA: 20/25
  • Visual function: Patient requires assistance from a caregiver on some activities (eg, cooking, driving)

FAF

Despite significant atrophy, the fovea is still partially intact

NIR

OCT

Significant atrophy outside the fovea as shown by choroidal hypertransmission defect

4 Years After

  • BCVA: 20/150
  • Visual function: Patient has stopped driving, and has trouble reading and seeing faces

FAF OS

NIR OS

OCT OS

Area of atrophy has grown, as shown by larger region of choroidal hypertransmission. The fovea still remains relatively spared

Images courtesy of Mohammad Rafieetary, OD, Charles Retina Institute.


BCVA=best-corrected visual acuity; BMI=body mass index; CFP=color fundus photography; FAF=fundus autofluorescence; INL=inner nuclear layer; NIR=near infrared reflectance; OCT=optical coherence tomography; OPL=outer plexiform layer; RPE=retinal pigment epithelium.

Find resources to help you and your patients with GA

Year 4

BCVA: 20/25
Choroidal hypertransmission defect indicative of atrophy.

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