Optical Coherence Tomography–Based Measurement of Drusen Load Predicts Development of Advanced Age-Related Macular Degeneration

doi:10.1016/j.ajo.2014.06.021

American Journal of Ophthalmology

Volume 158, Issue 4, October 2014, Pages 757-761.e1

https://doi.org/10.1016/j.ajo.2014.06.021 Get rights and content

Purpose

To determine whether baseline drusen load, as measured using spectral-domain optical coherence tomography (SD OCT), is a useful predictor of development of advanced age-related macular degeneration (AMD).

Design

Retrospective cohort study.

Methods

setting: Academic clinical practice. study population: All patients with non-neovascular AMD and no retinal pigment epithelial (RPE) atrophy at baseline who were seen between 2007 and 2012 in a single academic retina practice. A minimum of 1 year of follow-up was required. observation: Drusen load (area and volume) was assessed using automated SD OCT software algorithms. main outcome measure: RPE atrophy area, assessed using an automated SD OCT software algorithm, and the development of neovascular AMD.

Results

Eighty-three patients met the inclusion criteria with a mean age of 80 years and a mean follow-up time of 2.8 years. Repeated-measures analysis of variance showed an association between drusen area (P = .005) and drusen volume (P = .001) and the development of RPE atrophy. We also found an association between drusen area (P = .001) and drusen volume (P = .001) and the development of neovascular AMD.

Conclusions

Drusen load, as measured using SD OCT, is associated with the development of RPE atrophy and neovascular AMD. SD OCT assessments of drusen load are simple and practical measurements that may be useful in stratifying the risk of developing advanced AMD. These measurements have potential applications in both routine clinical care and clinical trials.

Section snippets

Study Population

We performed a retrospective chart review of all patients seen by the retina service at the University of British Columbia between December 2007 and December 2012. Ethics approval from the University of British Columbia Research Ethics Board was obtained. Eligibility criteria included the diagnosis of non-neovascular AMD in the study eye and a minimum of 1 year of follow-up. Study eyes were fellow eyes of eyes that had neovascular AMD and were being treated with anti-VEGF therapy using a

Results

Charts of 722 patients with AMD were reviewed to identify 83 patients who met the inclusion criteria. The mean follow-up time was 2.8 years (range 1.0–5.0, SD 1.1). Fifty-nine percent (49/83) of patients were female, and patients had a mean age of 80 years (SD 8). Mean drusen area at presentation was 0.59 mm² (SD 1.04) and mean drusen volume was 0.03 mm³ (SD 0.06). A total of 23 patients developed GA; the mean area of GA increased over time with average area of 0.02 mm² (SD 0.13) at baseline

Discussion

Our results confirm the previously observed conclusion that drusen load is predictive of progression to GA.4, 5, 6 However, this is the first study, to our knowledge, to demonstrate that automated SD OCT detection of drusen load, either using area or volume measurements, is also predictive of development of RPE atrophy. We did not find age to be a significant predictor, which is discrepant with other investigators4, 23, 24; this may have been attributable to varying definitions of GA (ie,

Dr Nawaaz A. Nathoo is currently a final year resident in the ophthalmology program at the University of British Columbia in Vancouver, Canada. His interests in ophthalmology span a variety of areas including medical education, anterior segment surgery, and pediatrics.

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Cited by (43)

Reticular Pseudodrusen on the Risk of Progression in Intermediate Age-Related Macular Degeneration
2022, American Journal of Ophthalmology
Citation Excerpt :
This study demonstrated that in our cohort of individuals with bilateral large drusen, followed with MMI every 6 months for up to 3 years, neither the presence of RPD defined on MMI at baseline, and any one of the individual imaging modalities, nor their baseline extent defined on combined NIR and OCT imaging, was associated with an increased risk of progression to MMI-defined late AMD in both univariable and multivariable analyses. These findings were observed in the same cohort where drusen volume and presence of pigmentary abnormalities were both significantly associated with disease progression, being parameters that are well established in previous studies as risk factors for progression.1,34-39 Our observation of a lack of a significant association between RPD and an increased risk of progression to late AMD was found both when late AMD was defined based on the traditionally defined endpoint of nAMD or GA, and when using a broader definition of MMI-defined late AMD that also included nGA29,30 in the definition of OCT-defined atrophy.
To examine the association between reticular pseudodrusen (RPD) and progression to late age-related macular degeneration (AMD) in individuals with intermediate AMD.
Prospective cohort study.
Two hundred eighty eyes from 140 participants with bilateral large drusen underwent multimodal imaging (MMI), including optical coherence tomography (OCT), near-infrared reflectance (NIR), fundus autofluorescence, and color fundus photography (CFP), at 6-monthly intervals up over a 36-month follow-up period. The presence of RPD per eye was determined based on either a combined MMI criterion, or each individual imaging modality, and their extent measured on combined OCT and NIR imaging. The association between the presence of RPD on different imaging modalities, and their extent, with the development of late AMD (including OCT-defined atrophy) was evaluated.
The presence of RPD on MMI, or any of its individual modalities, at baseline was not significantly associated with an increased rate of developing late AMD, with or without adjusting for risk factors for AMD progression (age, drusen volume on OCT, and pigmentary abnormalities on CFP; all P ≥ 0.205). The extent of RPD present was also not significantly associated with an increased rate of developing late AMD, with or without adjustment for risk factors for AMD progression (both P ≥ 0.522).
In this cohort with bilateral large drusen, the presence of RPD was not significantly associated with an increased risk of developing late AMD. Additional longitudinal studies in all stages of AMD are needed to understand the implications of RPD on vision loss in this condition.
Cuticular Drusen in Age-Related Macular Degeneration: Association with Progression and Impact on Visual Sensitivity
2022, Ophthalmology
Citation Excerpt :
Participants graded as having definitely present or questionable cuticular drusen were then reviewed by 2 retinal specialists (F.K.C. and C.B.), who determined the final grading of definitely present cuticular drusen together, with any disagreements immediately resolved by open adjudication. The CFPs were manually graded for the presence of pigmentary abnormalities (hyperpigmentary or hypopigmentary) and drusen volume on OCT imaging was calculated because these are 2 well-established risk factors for progression of AMD.2,33,34 OCT scans were analyzed to determine drusen volume (including cuticular drusen) in the entire 20° × 20° region, using a retinal layer segmentation algorithm on volume scans, based on a convolutional neural network-based approach as reported previously.35
To determine the prognostic significance and impact on visual function of the cuticular drusen phenotype in a cohort with intermediate age-related macular degeneration (AMD).
Longitudinal, observational study.
Participants aged 50 years or older, with bilateral large conventional drusen, without late AMD.
Multimodal imaging (MMI) and microperimetry were performed at baseline and then every 6 months for up to 3 years. Eyes were graded for the MMI-based presence of cuticular drusen at baseline. Color fundus photographs were used to grade for the presence of pigmentary abnormalities. OCT scans were used to calculate drusen volume. The associations between cuticular drusen and progression to MMI-defined late AMD (including OCT signs of atrophy) and the impact on visual sensitivity were examined with and without adjustment for the confounders of baseline age, pigmentary abnormalities, and drusen volume.
Time to develop MMI-defined late AMD and change in mean visual sensitivity.
A total of 280 eyes from 140 participants were included, with 70 eyes from 35 individuals (25%) having cuticular drusen at baseline. Cuticular drusen were not significantly associated with an increased rate of progression to late AMD with and without adjustment for confounders (P ≥ 0.784 for both). In an adjusted model, cuticular drusen were not associated with lower baseline visual sensitivity (P = 0.758) or a faster rate of visual sensitivity decline (P = 0.196).
In a cohort with bilateral large conventional drusen, individuals with the cuticular drusen phenotype had neither a higher nor lower risk of developing late AMD over 3 years and were not associated with a difference in rate of visual sensitivity decline compared with those without this phenotype. As such, individuals with this phenotype currently warrant similar monitoring strategies as those with conventional drusen.
Hyporeflective Cores within Drusen: Association with Progression of Age-Related Macular Degeneration and Impact on Visual Sensitivity
2022, Ophthalmology Retina
To examine the association between hyporeflective cores within drusen (HCD) and disease progression in age-related macular degeneration (AMD) and with visual function.
Longitudinal observational study.
Two hundred and eighty eyes from 140 participants with bilateral large drusen, without late AMD.
Multimodal imaging and microperimetry were performed at baseline and subsequently every 6 months for up to 3 years. Baseline OCT scans were graded for the presence of HCD and used to calculate drusen volume. The total area of the drusenoid lesions containing hyporeflective cores (HCD extent) on color fundus photographs (CFPs) was calculated. CFPs were also graded for the presence of pigmentary abnormalities. The association between HCD extent with progression to late AMD (including OCT signs of atrophy) and visual sensitivity measured using microperimetry at baseline and its rate of change over time was evaluated with and without adjustment for confounders of drusen volume, pigmentary abnormalities, and age.
Time to develop late AMD and visual sensitivity.
Twenty (7%) eyes from 12 (9%) individuals were found to have HCD at baseline, which was associated with a nonsignificantly increased rate of progression to late AMD (unadjusted P = 0.050). HCD extent was significantly associated with an increased rate of progression to late AMD (unadjusted P = 0.034) and lower visual sensitivity at baseline (unadjusted P < 0.001). However, these associations were no longer significant (P ≥ 0.264 for both) after adjusting for known risk factors for AMD progression. HCD extent was also not associated with a faster rate of visual sensitivity decline before the development of late AMD, with or without adjustment (P ≥ 0.674 for both). Increasing age and larger drusen volume were associated with HCD extent (P ≤ 0.041).
In a cohort with bilateral large drusen, HCD presence and extent were not independently associated with an increased rate of progression to late AMD over 3 years, nor with lower visual sensitivity or an increased rate of visual sensitivity decline before the development of late AMD, after adjusting for known risk factors for disease progression.
Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT
2021, Ophthalmology Retina
In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset.
Retrospective study.
Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants.
We analyzed longitudinally captured SD OCT images and color photographs from 488 eyes of 488 participants with intermediate AMD at baseline. Sixty-two eyes with sufficient image quality demonstrated new-onset GA on color photographs during study years 2 through 7. The area of new-onset GA and one size-matched control region in the same eye were segmented separately, and corresponding spatial volumes on registered SD OCT images at the GA incident year and at 2, 3, and 4 years previously were defined. Differences in SD OCT features between paired precursor regions were evaluated through matched-pairs analyses.
Localized SD OCT features 2 years before GA onset.
Compared with paired control regions, GA precursor regions at 2, 3, and 4 years before (n = 54, 33, and 25, respectively) showed greater drusen volume (P = 0.01, P = 0.003, and P = 0.003, respectively). At 2 and 3 years before GA onset, they were associated with the presence of hypertransmission (P < 0.001 and P = 0.03, respectively), hyperreflective foci (P < 0.001 and P = 0.045, respectively), OCT-reflective drusen substructures (P = 0.004 and P = 0.03, respectively), and loss or disruption of the photoreceptor zone, ellipsoid zone, and retinal pigment epithelium (RPE, P < 0.001 and P = 0.005–0.045, respectively). At 4 years before GA onset, precursor regions were associated with photoreceptor zone thinning (P = 0.007) and interdigitation zone loss (P = 0.045).
Evolution to GA is heralded by early local photoreceptor changes and drusen accumulation, detectable 4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable 1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials.
Predicting Progression of Age-Related Macular Degeneration Using OCT and Fundus Photography
2021, Ophthalmology Retina
Citation Excerpt :
The similarity of performance may have been expected because, in this specific setting, both approaches consider the same basic risk factors (drusen and RPE hyperpigmentary abnormalities) known to be associated with disease progression in AMD. However, it may also have been reasonable to expect that the method based on automatically derived OCT imaging biomarkers that quantifies the extent of these risk factors with a greater degree of granularity to provide improved performance for predicting progression, given that previous studies observed that the extent of these risk factors are associated with the risk of disease progression.5–11,27 We also observed in this study that a model based on drusen and HRF volume performed almost as well as a model that included additional factors such as mean and variability of drusen reflectivity, variability of RPE–drusen complex height, and HRF volume for different intraretinal locations.
To compare the performance of automatically quantified OCT imaging biomarkers and conventional risk factors manually graded on color fundus photographs for predicting progression to late age-related macular degeneration (AMD).
Longitudinal observational study.
Two hundred eighty eyes from 140 participants with bilateral large drusen.
All participants underwent OCT and color fundus photography (CFP) at baseline and were then reviewed at 6-month intervals to determine progression to late AMD. Color fundus photographs were graded manually and OCT scans underwent automated image analyses to quantify risk factors and imaging biomarkers, respectively, based on drusen and AMD pigmentary abnormalities. Four predictive models for progression to late AMD or atrophic AMD were only developed (each including age) based on: (1) CFP only (2 parameters); (2) OCT biomarkers, minimal (3 parameters); (3) OCT biomarkers, extended (7 parameters); and (4) CFP and OCT combined (8 parameters).
Predictive performance for progression to late AMD, examined based on the area under the receiver operating characteristic curve (AUC) for correctly predicting progression.
The AUC for predicting late AMD development was similar for the models based on CFP alone (model 1; 0.80), OCT alone (models 2 and 3; 0.82 for both), and when using both methods together (model 4; 0.85). In addition, these models also performed similarly for predicting the end point of atrophic AMD only (AUC, 0.83, 0.84, 0.85, and 0.88 for models 1, 2, 3, and 4, respectively).
OCT imaging biomarkers could provide an automatic method of risk stratification for progression to vision-threatening late AMD as well as manual grading of CFP.
Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration
2023, Acta Ophthalmologica

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Original articleOptical Coherence Tomography–Based Measurement of Drusen Load Predicts Development of Advanced Age-Related Macular Degeneration

Purpose

Design

Methods

Results

Conclusions

Section snippets

Study Population

Results

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Prog Neurobiol

Ophthalmology

Ophthalmology

Current knowledge and trends in age-related macular degeneration: today's and future treatments

Retina

Ranibizumab for neovascular age-related macular degeneration

N Engl J Med

Risk factors for choroidal neovascularization and geographic atrophy in the complications of age-related macular degeneration prevention trial

Ophthalmology

Original article
Optical Coherence Tomography–Based Measurement of Drusen Load Predicts Development of Advanced Age-Related Macular Degeneration