Relationship between Retinal Microstructures on Optical Coherence Tomography and Microperimetry in Age-Related Macular Degeneration

doi:10.1016/j.ophtha.2014.01.025

Ophthalmology

Volume 121, Issue 7, July 2014, Pages 1445-1452

https://doi.org/10.1016/j.ophtha.2014.01.025 Get rights and content

Purpose

To determine the relationship between structural parameters of the outer retina on spectral-domain optical coherence tomography (SD-OCT) and microperimetric retinal sensitivity in early stages of age-related macular degeneration (AMD).

Design

Prospective, observational study.

Participants

Seventy-five eyes of 75 participants with early stages of AMD (drusen ≥125 μm, with/without pigmentary abnormalities) and 25 control participants of a similar age.

Methods

Participants underwent microperimetry testing and high-resolution SD-OCT scans. Structural parameters at 5 central points (0°, 1°, and 2.33° nasal and temporal to the fovea along the horizontal axis) corresponding to areas tested by microperimetry were compared. Structural parameters included outer segment (OS) length, thickness and elevation of the retinal pigment epithelium (RPE) band, grading of the inner-segment ellipsoid (ISe) band integrity, and presence of hyperreflective foci (HF).

Main Outcome Measures

Relationship between structural parameters and retinal sensitivity.

Results

Retinal sensitivity was significantly correlated with RPE elevation (P < 0.001), ISe grading (P < 0.001), and presence of HF (P ≤ 0.018) at all test points, but not with OS length (P ≥ 0.093) or RPE thickness (P ≥ 0.125). However, multiple linear regression analyses revealed that only ISe grading (P ≤ 0.011) and RPE elevation (P ≤ 0.030) remained significantly associated with retinal sensitivity at all points. By using a simple linear model incorporating ISe grading and RPE elevation to predict values of retinal sensitivity, the 95% limits of agreement between the predicted and the actual value was ±3.83 dB.

Conclusions

The integrity of the ISe band and drusen-associated RPE elevation are significant independent predictors of microperimetric retinal sensitivity. Our findings imply that these 2 structural parameters may be surrogate markers of retinal function in the early stages of AMD.

Section snippets

Methods

This study was approved by the Human Research Ethics Committee of the Royal Victorian Eye and Ear Hospital and was conducted in accordance with the Declaration of Helsinki; written informed consent was obtained from all participants.

Results

A total of 75 participants with intermediate AMD were included in this study (68.2±8.5 years; range, 54–87 years), 53 (71%) of whom were female. Because all participants had intermediate AMD in both eyes, 1 eye was randomly selected to be the study eye; 35 right and 40 left eyes were included from these participants. Twenty-five control participants were included to determine the normal values for microperimetry (64.9±5.2 years; range, 50–73 years), 14 (66%) of whom were female; there were no

Discussion

This study showed that the integrity of the ISe band and RPE elevation were significant independent predictors of local changes in microperimetric retinal sensitivity, but not the OS length, RPE thickness, or presence of HF. By using a simple linear model that combined ISe grading and RPE elevation, the 95% limits of agreement between the predicted and measured retinal sensitivity is ±3.83 dB. The close correlation of these structural parameters with retinal function is ideal when considering

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Microperimetry and Structural Risk Factors on OCT in Intermediate Age-Related Macular Degeneration
2024, Ophthalmology Retina
To determine the relationship between structural biomarkers on OCT that increase the risk of disease progression and microperimetric retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD).
Prospective cross-sectional, observational study.
Forty-five eyes of 23 patients with iAMD.
Patients underwent OCT and microperimetry. OCT scans were evaluated for the risk factors intraretinal hyperreflective foci (HRF), hyporeflectivity within drusenoid lesions (HRDL), subretinal drusenoid deposits, double-layer sign (DLS), and drusen volume. Microperimetric retinal sensitivity was analyzed with a 33-point grid covering the macula. With a novel method of determining what part of the retina corresponded to each microperimetry point, a Voronoi diagram was constructed, dividing the macula in cells consisting of the region nearer to each point than any other. The Voronoi diagram was superimposed on the OCT, making it possible to determine the point-to-point location of the OCT risk factors. Univariable and multivariable linear mixed-effect models were used for analysis.
Association between microperimetric retinal sensitivity and OCT risk factors at individual measuring points.
One thousand four hundred seventy-nine points of retinal sensitivity and corresponding structural area on OCT were included in this study. Retinal sensitivity was significantly decreased with presence of the OCT risk factors HRF, HRDL, DLS, and drusen volume (all P < 0.001) when analyzed with the univariable linear mixed-effect model. The multivariable model showed a significant decrease of retinal sensitivity with presence of HRF (P < 0.001), DLS (P = 0.025), and greater drusen volume (P < 0.001).
Presence of HRF, DLS, and greater drusen volume, all of which increase the risk of disease progression, is significantly and independently associated with decreased microperimetric retinal sensitivity in patients with iAMD.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Changes of optical coherence tomographic hyperreflective foci in rhegmatogenous retinal detachment patients after successful surgery
2023, Photodiagnosis and Photodynamic Therapy
To assess the changes of hyperreflective foci (HRF) in rhegmatogenous retinal detachment (RRD) patients after successful reattachment surgery.
Twenty-nine macula-off RRD eyes with successful reattachment surgery were retrospectively analyzed. Optical coherence tomography (OCT) was used to image macular regions and measure HRF in outer retina and inner retina at 0.5, 1, 3, 6, 12 months after surgery. The relationships between HRF and photoreceptor layer status, visual outcomes were evaluated.
After retinal reattachment, HRF mainly distributed at the location where external limiting membrane (ELM) or inner and outer segment (IS/OS) line was disrupted. The HRF numbers in outer and inner retina were greater in eyes with discontinuous IS/OS line than eyes with continuous IS/OS line (all p<0.05). In the outer retina, HRF increased in the initial three months after retinal reattachment, and then decreased gradually after 3 months (p<0.05). The HRF number in the outer retina at postoperative 0.5 months was associated with favorable visual outcomes at 6 and 12 months (r=-0.487, p =0.025; r=-0.626, p=0.005, respectively), nevertheless, the HRF number at 3 months was correlated with poor visual results at 6 and 12 months (r=0.441, p =0.017; r=0.477, p=0.019, respectively).
HRF mainly occurred near the site where ELM or IS/OS line was injured after retinal reattachment. In the outer retina, the number of HRF gradually increased in the first 3 months and then gradually decreased. The early appearance of HRF in the outer retina was associated with a good visual prognosis, while the late appearance may suggest a less favorable visual outcome.
Cross-Sectional Study of Cone Function in Age-Related Macular Degeneration Subjects With Non-foveal Nascent Geographic Atrophy
2023, American Journal of Ophthalmology
To determine photoreceptor function in subjects with drusen only and non-foveal nascent geographic atrophy (nGA) intermediate age-related macular degeneration.
In this cross-sectional study, 60 eyes from 33 subjects, 30 with drusen only and 30 with non-foveal nGA determined by spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) underwent testing for best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), and qCSF algorithm (area under log contrast sensitivity function [AULCSF]) under both standard photopic and low-luminance (LL AULCSF) conditions. Areas of nGA-associated hypo-autofluorescence (hypo-AF) were graded.
In the drusen group, visual acuity (VA) = 81 letters ± 3 (mean ± SD), LLVA = 65 letters ± 4, AULCSF = 0.99 ± 0.0.5, and LL AULCSF = 0.38 ± 0.04, whereas in the nGA group, VA = 77 ± 4 letters, LLVA = 61± 4, AULCSF = 0.87 ± 0.09, and LL AULCSF = 0.28 ± 0.06. Multivariate analysis of variance among the LLVA, AULCSF, and LL AULCSF did not demonstrate a statistical difference (P = .167), whereas LL AULCSF analyzed by analysis of variance demonstrated a significant difference between the 2 groups (P = .037). Linear regressions demonstrated significant relationships between BCVA and AULCSF in both the drusen and nGA groups (r = 0.83, P < 10⁻⁹ and r = 0.61, P = .0004) but did not correlate with AULCSF under low-luminance conditions (r = 2.9, P = .13) in the nGA group. The total area of hypo-AF was negatively associated with poorer visual functions.
The use of LL AULCSF and certain features of FAF should be considered in clinical trials of intermediate age-related macular degeneration. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Natural History of the Relative Ellipsoid Zone Reflectivity in Age-Related Macular Degeneration
2022, Ophthalmology Retina
Relative ellipsoid zone reflectivity (rEZR) has been reported to be reduced in intermediate age-related macular degeneration (iAMD). However, longitudinal changes in rEZR remain unknown. This study investigated the natural history of rEZR in iAMD and its association with risk factors for disease progression, including the presence or extent of drusen volume, reticular pseudodrusen (RPD), and pigmentary abnormalities (PAs).
Longitudinal observational study.
Subjects with bilateral large drusen.
Spectral-domain (SD) OCT images of both eyes from each participant were obtained every 6 months for 3 years. Using an automated rEZR determination approach, the average rEZR of the central 20° macula was determined for each SD-OCT volume scan. Linear mixed models were used to determine the rate of change in rEZR with age (using the cross-sectional data at baseline) and over time (longitudinal data) and the interactions between the rate of rEZR changes with AMD risk factors at baseline.
Relative ellipsoid zone reflectivity and its rate of change with age and over time.
A total of 280 eyes from 140 individuals with bilateral large drusen were included in this study. Cross-sectional data showed that rEZR reduced with increasing age (−8.4 arbitrary units [AUs] per decade; 95% confidence interval [CI], −11.5 to −5.2; P < 0.001). Longitudinal data showed that, on average, rEZR declined at a rate of −2.1 AU per year (95% CI, −2.6 to −1.6 AU per year; P < 0.001). Larger RPD area (P = 0.042) at baseline was associated with a faster rate of rEZR decline over time, whereas the presence of PAs and the drusen volume at baseline showed no significant association with rEZR decline over time (P = 0.068 and P = 0.529, respectively).
The rEZR significantly reduces over 3 years in subjects with iAMD, and both the presence and increasing extent of coexistent RPD at baseline are associated with a faster rate of decline. These findings warrant further studies to understand the value of rEZR as a biomarker of AMD progression.
Longitudinal Evaluation of Visual Function Impairments in Early and Intermediate Age-Related Macular Degeneration Patients
2022, Ophthalmology Science
To evaluate visual function (VF) changes in early and intermediate age-related macular degeneration (eAMD and iAMD) over 24 months.
Prospective, observational natural history study.
Participants were enrolled at the Duke Eye Center.
A total of 101 subjects (33 with eAMD, 47 with iAMD, and 21 normal controls) were recruited. Visual function (VF) tests included best-corrected visual acuity (BCVA), low- luminance visual acuity (LLVA), microperimetry (MP), cone contrast tests (CCTs), and dark adaptation (DA). Mixed-effect model repeated measures based on absolute values and change from baseline identified VF tests differentiating AMD from controls and revealing longitudinal VF decline when controlling for covariates (baseline value, age, coronary artery disease, dry eye, and phakic status). Nine AMD genetic risk variants, combinations of these (genetic burden score), reticular pseudodrusen (RPD), and hyperreflective foci (HRF) were tested as predictors of diagnosis and VF performance.
Longitudinal changes in VF metrics over 24 months.
A total of 70 subjects completed the 2-year visit (22 with eAMD, 31 with iAMD, and 17 controls). Percent reduced threshold (PRT) on MP and CCT red significantly distinguished iAMD versus controls after 12 and 24 months, respectively. Cone contrast test red, PRT, and absolute threshold (AT) on MP showed significant longitudinal deterioration of VF in iAMD versus baseline at 12 months and onward, however, with a reduced rate of worsening. The DA data confirmed a preexisting functional deficit in iAMD at baseline and revealed an increasing proportion of poorly performing iAMD subjects in DA over the study period. None of the other VF measures showed consistent significant changes among the normal, early, and intermediate groups or over time. The genetic burden score was significantly associated with AMD diagnosis (relative risk for iAMD = 1.64, P < 0.01) and DA (r = 0.42, P = 0.00005). Reticular pseudodrusen and HRF showed moderate associations with DA and weak to moderate associations with MP variables.
In iAMD, MP variables, CCT red, and DA revealed slow and nonlinear functional decline over 24 months. A structure–function relationship in eAMD and iAMD stages was demonstrated among HRF, RPD, and DA, possibly modified by genetic risk factors. These structural and functional features represent potential end points for clinical trials in iAMD.
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The currently used measures of retinal function are limited by being subjective, nonlocalized, or taxing for patients. To address these limitations, we sought to develop and evaluate a deep learning (DL) method to automatically predict the functional end point (retinal sensitivity) based on structural OCT images.
Retrospective, cross-sectional study.
In total, 714 volumes of 289 patients were used in this study.
A DL algorithm was developed to automatically predict a comprehensive retinal sensitivity map from an OCT volume. Four hundred sixty-three spectral-domain OCT volumes from 174 patients and their corresponding microperimetry examinations (Nidek MP-1) were used for development and internal validation, with a total of 15 563 retinal sensitivity measurements. The patients presented with a healthy macula, early or intermediate age-related macular degeneration, choroidal neovascularization, or geographic atrophy. In addition, an external validation was performed using 251 volumes of 115 patients, comprising 3 different patient populations: those with diabetic macular edema, retinal vein occlusion, or epiretinal membrane.
We evaluated the performance of the algorithm using the mean absolute error (MAE), limits of agreement (LoA), and correlation coefficients of point-wise sensitivity (PWS) and mean sensitivity (MS).
The algorithm achieved an MAE of 2.34 dB and 1.30 dB, an LoA of 5.70 and 3.07, a Pearson correlation coefficient of 0.66 and 0.84, and a Spearman correlation coefficient of 0.68 and 0.83 for PWS and MS, respectively. In the external test set, the method achieved an MAE of 2.73 dB and 1.66 dB for PWS and MS, respectively.
The proposed approach allows the prediction of retinal function at each measured location directly based on an OCT scan, demonstrating how structural imaging can serve as a surrogate of visual function. Prospectively, the approach may help to complement retinal function measures, explore the association between image-based information and retinal functionality, improve disease progression monitoring, and provide objective surrogate measures for future clinical trials.

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: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: Supported by the National Health and Medical Research Council (NH&MRC) Project Grant (1027624), NH&MRC practitioner fellowship (RHG, #529905), Macular Disease Foundation Australia Research Grant, Bupa Health Foundation (Australia), William Angliss (Victoria) Charitable Fund Research Grant, BrightFocus Foundation, The Perpetual Trust Foundation and MR & RA Brownless Perpetual Charitable Trust funding administered by the Trust Company. The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian Government. This study was supported by the NH&MRC Centre for Clinical Research Excellence #529923 – Translational Clinical Research in Major Eye Diseases.

^∗: C.D.L. and R.H.G. contributed equally as senior authors.

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Original articleRelationship between Retinal Microstructures on Optical Coherence Tomography and Microperimetry in Age-Related Macular Degeneration

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Methods

Results

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography

Ophthalmology

Abnormal thickening as well as thinning of the photoreceptor layer in intermediate age-related macular degeneration

Invest Ophthalmol Vis Sci

Relationship between outer retinal thickness substructures and visual acuity in eyes with dry age-related macular degeneration

Invest Ophthalmol Vis Sci

Relationship between retinal layer thickness and the visual field in early age-related macular degeneration

Invest Ophthalmol Vis Sci

Effect of change in drusen evolution on photoreceptor inner segment/outer segment junction

Retina

Scanning laser ophthalmoscope imaging stabilized microperimetry in dry age-related macular degeneration

Retina

Drusen characteristics revealed by spectral-domain optical coherence tomography and their corresponding fundus autofluorescence appearance in dry age-related macular degeneration

Ophthalmic Res

Inner segment–outer segment junctional layer integrity and corresponding retinal sensitivity in dry and wet forms of age-related macular degeneration

Retina

Second reflective band intensity in age-related macular degeneration

Ophthalmology

Relationship between the second reflective band on optical coherence tomography and multifocal electroretinography in age-related macular degeneration

Invest Ophthalmol Vis Sci

Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration

Br J Ophthalmol

Quantitative comparison of drusen segmented on SD-OCT versus drusen delineated on color fundus photographs

Invest Ophthalmol Vis Sci

Spatial correlation between hyperpigmentary changes on color fundus photography and hyperreflective foci on SDOCT in intermediate AMD

Invest Ophthalmol Vis Sci

Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium

Invest Ophthalmol Vis Sci

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration patients treated with ranibizumab

Retina

Macular function in macular degenerations: repeatability of microperimetry as a potential outcome measure for ABCA4-associated retinopathy trials

Invest Ophthalmol Vis Sci

Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial

Invest Ophthalmol Vis Sci

Original article
Relationship between Retinal Microstructures on Optical Coherence Tomography and Microperimetry in Age-Related Macular Degeneration