To quantitatively measure hyperreflective foci (HRF) during the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using deep learning (DL) and investigate the ...association with local and global growth of GA.
Eyes with GA were prospectively included. Spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence images were acquired every 6 months. A 500-μm-wide junctional zone adjacent to the GA border was delineated and HRF were quantified using a validated DL algorithm. HRF concentrations in progressing and nonprogressing areas, as well as correlations between HRF quantifications and global and local GA progression, were assessed.
A total of 491 SDOCT volumes from 87 eyes of 54 patients were assessed with a median follow-up of 28 months. Two-thirds of HRF were localized within a millimeter adjacent to the GA border. HRF concentration was positively correlated with GA progression in unifocal and multifocal GA (all P < .001) and de novo GA development (P = .037). Local progression speed correlated positively with local increase of HRF (P value range <.001-.004). Global progression speed, however, did not correlate with HRF concentrations (P > .05). Changes in HRF over time did not have an impact on the growth in GA (P > .05).
Advanced artificial intelligence (AI) methods in high-resolution retinal imaging allows to identify, localize, and quantify biomarkers such as HRF. Increased HRF concentrations in the junctional zone and future macular atrophy may represent progressive migration and loss of retinal pigment epithelium. AI-based biomarker monitoring may pave the way into the era of individualized risk assessment and objective decision-making processes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
To investigate the impact of subretinal drusenoid deposits (SDD) and photoreceptor integrity on global and local geographic atrophy (GA) progression.
Eighty-three eyes of 49 patients, aged 50 years ...and older with GA secondary to age-related macular degeneration (AMD), were prospectively included in this study. Participants underwent spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging at baseline and after 12 months. The junctional zone and presence of SDD were delineated on SD-OCT and FAF images. Linear mixed models were calculated to investigate the association between GA progression and the junctional zone area, baseline GA area, age, global and local presence of SDD and unifocal versus multifocal lesions.
The area of the junctional zone was significantly associated with the progression of GA, both globally and locally (all P < 0.001). SDD were associated with faster growth in the overall model (P = 0.039), as well as in the superior-temporal (P = 0.005) and temporal (P = 0.002) sections. Faster progression was associated with GA baseline area (P < 0.001). No difference was found between unifocal and multifocal lesions (P > 0.05). Age did not have an effect on GA progression (P > 0.05).
Photoreceptor integrity and SDD are useful for predicting global and local growth in GA. Investigation of the junctional zone is merited because this area is destined to become atrophic. Photoreceptor loss visible on SD-OCT might lead to new structural outcome measurements visible before irreversible loss of retinal pigment epithelium occurs.
Retinal fluid as the major biomarker in exudative macular disease is accurately visualized by high-resolution three-dimensional optical coherence tomography (OCT), which is used world-wide as a ...diagnostic gold standard largely replacing clinical examination. Artificial intelligence (AI) with its capability to objectively identify, localize and quantify fluid introduces fully automated tools into OCT imaging for personalized disease management. Deep learning performance has already proven superior to human experts, including physicians and certified readers, in terms of accuracy and speed. Reproducible measurement of retinal fluid relies on precise AI-based segmentation methods that assign a label to each OCT voxel denoting its fluid type such as intraretinal fluid (IRF) and subretinal fluid (SRF) or pigment epithelial detachment (PED) and its location within the central 1-, 3- and 6-mm macular area. Such reliable analysis is most relevant to reflect differences in pathophysiological mechanisms and impacts on retinal function, and the dynamics of fluid resolution during therapy with different regimens and substances. Yet, an in-depth understanding of the mode of action of supervised and unsupervised learning, the functionality of a convolutional neural net (CNN) and various network architectures is needed. Greater insight regarding adequate methods for performance, validation assessment, and device- and scanning-pattern-dependent variations is necessary to empower ophthalmologists to become qualified AI users. Fluid/function correlation can lead to a better definition of valid fluid variables relevant for optimal outcomes on an individual and a population level. AI-based fluid analysis opens the way for precision medicine in real-world practice of the leading retinal diseases of modern times.
•The current assessment of optical coherence tomography images in clinical practice is unsatisfactory.•Artificial intelligence offers objective and precise localization and quantification of fluid.•Automated algorithms provide identification of different types and dynamics of fluid resolution.•The performance of advanced AI tools is superior to human experts in terms of accuracy and speed.•AI in retinal fluid analysis introduces precision medicine into real-world patient management.
Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement ...inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.
Microperimetry (MP) is a psychometric examination combining retinal imaging and functional sensitivity testing with an increasing importance due to its potential use as clinical study outcome. We ...investigated the repeatability of pointwise retinal sensitivity (PWS) on the most advanced commercially available MP devices under their standard setting in a healthy aging population. Two successive MP examinations on both MP-3 (NIDEK CO., Ltd., Gamagori, Japan) and MAIA (CenterVue S.p.A. (iCare), Padova, Italy) were performed on healthy aging subjects in a randomized order. PWS repeatability was analysed for different macular regions and age groups using Bland-Altmann coefficients of repeatability (CoR). A total of 3600 stimuli from 20 healthy individuals with a mean age of 70 (11) years were included. Mean CoR in dB were ±4.61 for MAIA and ±4.55 for MP-3 examinations. A lower repeatability (p=0.005) was detected in the central millimetre on MAIA examinations. Higher subject age was associated with a lower repeatability of PWS on both devices (both p=0.003). Intra-device correlation was good (MAIA: 0.79 0.76-0.81; MP-3: 0.72 0.68-0.76) whereas a moderate mean inter-device correlation (0.6 0.55-0.65) could be detected. In conclusion, older subjects and the foveal region are associated with a worse pointwise repeatability.
To assess the influence of the SARS-CoV-2 lockdown in spring on frequency, severity and quality of care of rhegmatogeneous retinal detachments (RRD) in a tertiary referral center in Vienna, Austria.
...Single center, consecutive case series with historical controls. Patients presenting with primary RRD during the first Austrian SARS-CoV-2 lockdown (March 16th-May 3rd 2020) and a corresponding control group consisting of the same time period of the preceding 3 years.
The mean number of patients with RD in the reference group (RG) was 22 (± 1) and in the lockdown group (LG) 15. Median total delay, defined as onset of symptoms until surgery, in the RG was 5 (lower quartile: 3.0; upper quartile: 8.0) compared to 7 (3.0; 12.0) days in the LG, (p = 0.740). During the lockdown 67% of patients were referred from an external ophthalmologist compared to 52% in the RG, (p = 0.395). 34% of patients in the RG presented with an attached macula compared to 33% in the LG (p = 0.597). PVR was present in 49% of cases in the RG compared to 73% in the LG. Single surgery success (SSS) rates were lower in the LG (73.3%) compared to the RG (85.3%), (p = 0.275).
Patients with RRD during the SARS-CoV-2 lockdown presented and were treated within acceptable time limits, showed the same macula-on ratios but a higher PVR rate and a tendency towards worse SSS rates compared to the time period of the preceding 3 years.
To perform an optical coherence tomography (OCT)-based analysis of geographic atrophy (GA) progression in patients treated with pegcetacoplan.
Post hoc analysis of a phase 2 multicenter, randomized, ...sham-controlled trial.
Manual annotation of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss was performed on OCT volumes from baseline and month 12 from the phase 2 FILLY trial of intravitreal pegcetacoplan for the treatment of GA secondary to age-related macular degeneration.
Correlation of GA areas measured on fundus autofluorescence and OCT. Difference in square root transformed growth rates of RPE, EZ, and ELM loss between treatment groups (monthly injection AM, injection every other month AEOM, and sham SM).
OCT volumes from 113 eyes of 113 patients (38 AM, 36 AEOM, and 39 SM) were included, resulting in 11 074 B-scans. The median growth of RPE loss was significantly slower in the AM group (0.158 0.057-0.296) than the SM group (0.255 0.188-0.359, P = .014). Importantly, the growth of EZ loss was also significantly slower in the AM group (0.127 0.041-0.247) than the SM group (0.232 0.130-0.349, P = .017). There was no significant difference in the growth of ELM loss between the treatment groups (P = .114).
OCT imaging provided consistent results for GA growth compared with fundus autofluorescence. In addition to slower RPE atrophy progression in patients treated with pegcetacoplan, a significant reduction in EZ impairment was also identified by OCT, suggesting the use of OCT as a potentially more sensitive monitoring tool in GA therapy.
To assess the therapeutic response to brolucizumab and aflibercept by deep learning/OCT-based analysis of macular fluid volumes in neovascular age-related macular degeneration.
In this post-hoc ...analysis of two phase III, randomised, multi-centre studies (HAWK/HARRIER), 1078 and 739 treatment-naive eyes receiving brolucizumab or aflibercept according to protocol-specified criteria in HAWK and HARRIER, respectively, were included. Macular fluid on 41,840 OCT scans was localised and quantified using a validated deep learning-based algorithm. Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED) for all central macular areas (1, 3 and 6 mm) in nanolitres (nL) and best corrected visual acuity (BCVA) change in ETDRS letters were associated using mixed models for repeated measures.
Baseline IRF volumes decreased by >92% following the first intravitreal injection and consistently remained low during follow-up. Baseline SRF volumes decreased by >74% following the first injection, while PED volume resolved by 68-79% of its baseline volume. Resolution of SRF and PED was dependent on the substance and regimen used. Larger residual post-loading IRF, SRF and PED volumes were all independently associated with progressive vision loss during maintenance, where the differences in mean BCVA change between high and low fluid volume subgroups for IRF, SRF and PED were 3.4 letters (p < 0.0001), 1.7 letters (p < 0.001) and 2.5 letters (p < 0.0001), respectively.
Deep-learning methods allow an accurate assessment of substance and regimen efficacy. Irrespectively, all fluid compartments were found to be important markers of disease activity and were relevant for visual outcomes.
Purpose
The purpose of the study was to compare ultrasound (US) consumption and central macular thickness (CMT) and volume changes with manual and femtosecond laser (FSL)‐assisted cataract nucleus ...workup.
Methods
Sixty patients scheduled for immediate sequential bilateral surgery underwent a prospective randomized intraindividual comparison of nucleus sector fragmentation performed manually in one eye and with low‐energy FSL assistance in the partner eye, followed by high‐fluidics phacoaspiration with a maximum US power of 30%. Ultrasound (US) energy consumption and macular thickness and volume were compared as measured by intraoperative effective phacoemulsification time (EPT) and high‐resolution spectral domain optical coherence tomography pre‐ and 1 week, 3 weeks and 6 weeks postoperatively. Results are presented as means ± SD or medians min; max.
Results
Fifty‐two patients completed the full follow‐up. For the manual and FSL‐assisted groups, nuclear hardness was almost identical with a mean LOCS III grade of 2.44 ± 1.08 and 2.50 ± 1.00 (p = 0.371). Median EPT was 1.40 0.2; 8.3 and 1.25 0.2; 9.4 seconds. Median preoperative CMT was 276.50 263.25; 289.75 µm and 276.00 262.00; 290.00 µm. Median postoperative CMT was 278.00 260.50; 288.00 versus 275.50 264.00; 290.50 µm at 1 week, 279.50 266.75; 292.25 versus 280.00 266.50; 294.50 µm at 3 weeks and 280.50 268.00, 293.75 versus 279.50 264.75; 295.25 µm at 6 weeks. Differences in CMT and total macular volume between the groups were not statistically significant at any point in time.
Conclusion
Femtosecond laser (FSL) prefragmentation of the nucleus into six sectors did not reduce US energy consumption compared with manual splitting of the nucleus into four quadrants in this particular surgical setting. Sectorial FSL‐prechopping with the low‐energy FSL used had no additional impact on postoperative macular thickness and volume.
To investigate associations between residual subretinal fluid (rSRF) volumes, quantified using artificial intelligence and treatment outcomes in a subretinal fluid (SRF)-tolerant treat-and-extend ...(T&E) regimen in neovascular age-related macular degeneration.
Patients enrolled in the prospective, multicenter FLUID study randomized in an SRF-tolerant T&E regimen were examined by spectral-domain optical coherence tomography and tested for best-corrected visual acuity (BCVA). Intraretinal fluid and SRF volumes were quantified using artificial intelligence tools. In total, 375 visits of 98 patients were divided into subgroups: extended intervals despite rSRF and extended intervals without fluid. Associations between BCVA change, SRF volume, subgroups, and treatment intervals were estimated using linear mixed models.
In extended intervals despite rSRF, increased SRF was associated with reduced BCVA at the next visit in the central 1 mm (-0.138 letters per nL; P = 0.014) and 6 mm (-0.024 letters per nL; P = 0.049). A negative association between increased interval and BCVA change was found for rSRF in 1 mm and 6 mm (-0.250 and -0.233 letter per week interval, respectively; both P < 0.001). Extended intervals despite rSRF had significantly higher SRF volumes in the central 6 mm at the following visit (P = 0.002).
Artificial intelligence-based analysis of extended visits despite rSRF demonstrated increasing SRF volumes associated with BCVA loss at the consecutive visit. This negative association contributes to the understanding of rSRF volumes on treatment outcomes in neovascular age-related macular degeneration.
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