In this paper, we propose a novel classification model for automatically identifying individuals with age-related macular degeneration (AMD) or Diabetic Macular Edema (DME) using retinal features ...from Spectral Domain Optical Coherence Tomography (SD-OCT) images. Our classification method uses retinal features such as the thickness of the retina and the thickness of the individual retinal layers, and the volume of the pathologies such as drusen and hyper-reflective intra-retinal spots. We extract automatically, ten clinically important retinal features by segmenting individual SD-OCT images for classification purposes. The effectiveness of the extracted features is evaluated using several classification methods such as Random Forrest on 251 (59 normal, 177 AMD and 15 DME) subjects. We have performed 15-fold cross-validation tests for three phenotypes; DME, AMD and normal cases using these data sets and achieved accuracy of more than 95% on each data set with the classification method using Random Forrest. When we trained the system as a two-class problem of normal and eye with pathology, using the Random Forrest classifier, we obtained an accuracy of more than 96%. The area under the receiver operating characteristic curve (AUC) finds a value of 0.99 for each dataset. We have also shown the performance of four state-of-the-methods for classification the eye participants and found that our proposed method showed the best accuracy.
Age-related macular degeneration Guymer, Robyn H; Campbell, Thomas G
The Lancet (British edition),
04/2023, Volume:
401, Issue:
10386
Journal Article
Peer reviewed
Age-related macular degeneration is an increasingly important public health issue due to ageing populations and increased longevity. Age-related macular degeneration affects individuals older than 55 ...years and threatens high-acuity central vision required for important tasks such as reading, driving, and recognising faces. Advances in retinal imaging have identified biomarkers of progression to late age-related macular degeneration. New treatments for neovascular age-related macular degeneration offer potentially longer-lasting effects, and progress is being made towards a treatment for atrophic late age-related macular degeneration. An effective intervention to slow progression in the earlier stages of disease, or to prevent late age-related macular degeneration development remains elusive, and our understanding of underlying mechanistic pathways continues to evolve.
To report 24-month outcomes of anti-vascular endothelial growth factor (VEGF) therapy for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) using a treat and extend ...treatment regimen in routine clinical practice.
Database observational study.
We included treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice treated using a treat and extend regimen that were tracked in the Fight Retinal Blindness observational registry.
A cohort of eyes treated by practitioners using exclusively a treat and extend regimen was extracted from the Fight Retinal Blindness observational registry.
Change in visual acuity (VA) over 2 years and number of injections and visits.
Data from 1198 eyes from 1011 patients receiving anti-VEGF therapy using a treat and extend regimen for treatment-naïve nAMD between January 2007 and December 2012 and with 24-month follow-up were included in the analysis. Mean VA increased by +5.3 logarithm of the minimum angle of resolution letters from 56.5 letters (20/80+1) at initial visit to 61.8 (20/60+2) letters at 24 months. Mean VA gains improved and number of injections increased with successive years from +2.7 letters for eyes commencing in 2007 after a mean of 9.7 injections in 2 years, to +7.8 letters for eyes commencing in 2012 after a mean of 14.2 injections over 2 years. The proportion of eyes with VA >20/40 increased from 27% when starting treatment to 45% after 24 months; the proportion with vision of <20/200 remained unchanged (13% initial, 11% at 24 months). Of the included eyes, 90.5% avoided a vision loss of ≥15 letters. There was an overall mean of 13.0 injections over the 24 months, 7.5 injections in the first year and 5.5 in the second year, with a mean of 14.8 clinic visits.
These data indicate that eyes managed in routine clinical practice with a treat and extend regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.
We present a novel framework combining convolutional neural networks (CNN) and graph search methods (termed as CNN-GS) for the automatic segmentation of nine layer boundaries on retinal optical ...coherence tomography (OCT) images. CNN-GS first utilizes a CNN to extract features of specific retinal layer boundaries and train a corresponding classifier to delineate a pilot estimate of the eight layers. Next, a graph search method uses the probability maps created from the CNN to find the final boundaries. We validated our proposed method on 60 volumes (2915 B-scans) from 20 human eyes with non-exudative age-related macular degeneration (AMD), which attested to effectiveness of our proposed technique.
Reticular pseudodrusen (RPD), or subretinal drusenoid deposits (SDD), refer to distinct lesions that occur in the subretinal space. Over the past three decades, their presence in association with ...age-related macular degeneration (AMD) has become increasingly recognized, especially as RPD have become more easily distinguished with newer clinical imaging modalities. There is also an increasing appreciation that RPD appear to be a critical AMD phenotype, where understanding their pathogenesis will provide further insights into the processes driving vision loss in AMD. However, key barriers to understanding the current evidence related to the independent impact of RPD include the heterogeneity in defining their presence, and failure to account for the confounding impact of the concurrent presence and severity of AMD pathology. This review thus critically discusses the current evidence on the prevalence and clinical significance of RPD and proposes a clinical imaging definition of RPD that will help move the field forward in gathering further key knowledge about this critical phenotype. It also proposes a putative mechanism for RPD formation and how they may drive progression to vision loss in AMD, through examining current evidence and presenting novel findings from preclinical and clinical studies.
To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration.
Twelve-month, phase III, multicenter, open-label, single-arm ...study.
A total of 513 ranibizumab-naïve SUSTAIN patients.
Three initial monthly injections of ranibizumab (0.3 mg) and thereafter pro re nata (PRN) retreatment for 9 months based on prespecified retreatment criteria. Patients switched to 0.5 mg ranibizumab after approval in Europe.
Frequency of adverse events (AEs), monthly change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline, the time to first re-treatment, and the number of treatments were assessed.
A total of 249 patients (48.5%) reported ocular AEs, and 8 (1.5%) deaths, 5 (1.2%) patients with ocular serious AEs of the study eye (retinal hemorrhage, cataract, retinal pigment epithelial tear, reduced visual acuity VA, vitreous hemorrhage), and 19 (3.7%) patients with arteriothromboembolic events were observed. Most frequent AEs in the study eye were reduced VA (18.5%), retinal hemorrhage (7.2%), increased intraocular pressure (7.0%), and conjunctival hemorrhage (5.5%). The average number of re-treatments from months 3 to 11 was 2.7. Mean best-corrected visual acuity increased steadily from baseline to month 3 to reach +5.8 letters, decreased slightly from month 3 to 6, and remained stable from month 6 to 12, reaching +3.6 at month 12. Mean change in CRT was -101.1 μm from baseline to month 3 and -91.5 μm from baseline to month 12.
The safety results are comparable to the favorable tolerability profile of ranibizumab observed in previous pivotal clinical studies; individualized treatment with less than monthly re-treatments shows a similar safety profile as observed in previous randomized clinical trials with monthly ranibizumab treatment. Efficacy outcomes were achieved with a low average number of re-treatments. Visual acuity in SUSTAIN patients with individualized re-treatment based on VA/optical coherence tomography assessment reached on average a maximum after the first 3 monthly injections, decreased slightly under PRN during the next 2 to 3 months, and was then sustained throughout the treatment period.
To determine the histologic and cellular correlates in the retina and retinal pigment epithelium (RPE) with the presence of optical coherence tomography-defined reticular pseudodrusen (RPD).
...Observation case using immunocytochemistry of an exenterated eye with immediate fixation after removal.
Two patients, one with confirmed RPD and the other with mid-peripheral drusen, underwent multimethod imaging before exenteration and immediate fixation of the posterior eyecup for high-resolution immunocytochemical analysis.
Optical coherence tomography (OCT) was compared with high-resolution immunocytochemistry using a range of cellular markers to determine changes in the RPE, photoreceptors, and gliosis.
Correlations of the appearance of reticular pseudodrusen on OCT and immunocytochemical analysis.
Reticular pseudodrusen were deposits juxtaposed to photoreceptor outer segments extending through the outer nuclear layer and even beyond the outer limiting membrane. Deposits were rich in vitronectin, photoreceptor-associated proteins, and Iba1-immunoreactive immune cells. In contrast to conventional drusen the lipid stain Oil Red O failed to stain RPD. Cellular analysis revealed that RPD were associated with photoreceptor disruption and loss and localized gliosis. In addition, anomalies in the RPE were observed.
Reticular pseudodrusen represent subretinal deposits that extend through the outer nuclear layer, affect photoreceptor integrity, and are associated with retinal gliosis and RPE damage.
To assess outcomes of the treat-and-extend (T&E) injection regimen for neovascular age-related macular degeneration (AMD) as compared to either a monthly or a pro re nata (PRN) treatment strategy.
...Systematic review and meta-analysis.
Studies that compared the T&E regimen with either monthly or PRN dosing for treatment-naïve AMD were included. Trial eligibility, data extraction, and risk of bias were assessed according to Cochrane review methods. Estimates were pooled using random-effects meta-analysis.
Four eligible studies were identified, all using ranibizumab (total N = 940 eyes), including 2 randomized controlled trials comparing T&E to monthly and 2 retrospective reviews comparing T&E to PRN. No studies evaluating aflibercept were identified. Improvements in vision and central retinal thickness were similar between T&E and monthly at 12 months, with a mean difference of -1.79 letters (95% confidence interval CI: 3.70, 0.13) and 3.76 μm (95% CI: -13.78, 21.30) in favor of monthly injections. In contrast, visual gains were higher in the T&E compared to the PRN group (difference of +6.18 letters, 95% CI: 3.28, 9.08). Fewer injections were required using the T&E regimen when compared to monthly (mean of -1.6 and -6.9 injections at 12 and 24 months, respectively). A mean of 1.44 more injections was required for the T&E compared to PRN regimen at 12 months; however, this was achieved with fewer visits.
Despite the growing preference for the T&E regimen, there is limited head-to-head evidence comparing dosing strategies. The evidence available, however, suggests that at 12 months, T&E is comparable to monthly and superior to PRN dosing for both efficacy and safety outcomes when using ranibizumab.
Emergence of the high‐resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. ...However, some anatomical correlates still remain contentious, such as the second hyper‐reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications.