Age-Related Macular Degeneration Detection and Stage Classification Using Choroidal OCT Images

In this paper, we propose a machine learning based method to detect AMD and distinguish the di↵erent stages using choroidal images obtained from optical coherence tomography (OCT). We extract texture features using a Gabor filter bank and non-linear energy transformation. Then the histogram based feature descriptors are used to train the random forests, Support Vector Machine (SVM) and neural networks, which are tested on our choroid OCT image dataset with 21 participants

Optical Coherence Tomographic Angiography Imaging in Age-Related Macular Degeneration.

Optical coherence tomographic angiography (OCTA) is emerging as a rapid, noninvasive imaging modality that can provide detailed structural and flow information on retinal and choroidal vasculature. This review contains an introduction of OCTA and summarizes the studies to date on OCTA imaging in age-related macular degeneration

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques.

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes - 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruchs membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates

The Role of Medical Image Modalities and AI in the Early Detection, Diagnosis and Grading of Retinal Diseases: A Survey.

Traditional dilated ophthalmoscopy can reveal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular edema (DME), retinal tear, epiretinal membrane, macular hole, retinal detachment, retinitis pigmentosa, retinal vein occlusion (RVO), and retinal artery occlusion (RAO). Among these diseases, AMD and DR are the major causes of progressive vision loss, while the latter is recognized as a world-wide epidemic. Advances in retinal imaging have improved the diagnosis and management of DR and AMD. In this review article, we focus on the variable imaging modalities for accurate diagnosis, early detection, and staging of both AMD and DR. In addition, the role of artificial intelligence (AI) in providing automated detection, diagnosis, and staging of these diseases will be surveyed. Furthermore, current works are summarized and discussed. Finally, projected future trends are outlined. The work done on this survey indicates the effective role of AI in the early detection, diagnosis, and staging of DR and/or AMD. In the future, more AI solutions will be presented that hold promise for clinical applications

Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally

Comparison of retinal regions-of-interest imaged by OCT for the classification of intermediate AMD

To study whether it is possible to differentiate intermediate age-related macular degeneration (AMD) from healthy controls using partial optical coherence tomography (OCT) data, that is, restricting the input B-scans to certain pre-defined regions of interest (ROIs). A total of 15744 B-scans from 269 intermediate AMD patients and 115 normal subjects were used in this study (split on subject level in 80% train, 10% validation and 10% test). From each OCT B-scan, three ROIs were extracted: retina, complex between retinal pigment epithelium (RPE) and Bruch membrane (BM), and choroid (CHO). These ROIs were obtained using two different methods: masking and cropping. In addition to the six ROIs, the whole OCT B-scan and the binary mask corresponding to the segmentation of the RPE-BM complex were used. For each subset, a convolutional neural network (based on VGG16 architecture and pre-trained on ImageNet) was trained and tested. The performance of the models was evaluated using the area under the receiver operating characteristic (AUROC), accuracy, sensitivity, and specificity. All trained models presented an AUROC, accuracy, sensitivity, and specificity equal to or higher than 0.884, 0.816, 0.685, and 0.644, respectively. The model trained on the whole OCT B-scan presented the best performance (AUROC = 0.983, accuracy = 0.927, sensitivity = 0.862, specificity = 0.913). The models trained on the ROIs obtained with the cropping method led to significantly higher outcomes than those obtained with masking, with the exception of the retinal tissue, where no statistically significant difference was observed between cropping and masking (p = 0.47). This study demonstrated that while using the complete OCT B-scan provided the highest accuracy in classifying intermediate AMD, models trained on specific ROIs such as the RPE-BM complex or the choroid can still achieve high performance

Identification of Surrogate Anatomic Identifiers of Disease Progression in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of vision loss in patients over 50 in the developed world. The visual impairment is due to either choroidal neovascularisation (wet AMD) or geographic atrophy (GA). Drusen is the hallmark of AMD but the presence of drusen does not inform progression to wet AMD. Although the disease is mostly bilateral, the rate of progression of disease in both eyes may not be simultaneous. If one eye is affected by wet AMD, the risk of progression of the fellow eye to wet AMD increases by 10% every year. However, there are no markers that inform the time of conversion to wet AMD. For this reason, there is an unmet need to identify biomarkers that can fully predict the progression to wet AMD in order to allow early intervention before permanent damage. My thesis aimed to assess whether changes in imaging characteristics can more precisely explain conversion. I studied various cohorts including (a) normal aging eyes (b) eyes with early/ intermediate AMD and (c) fellow eyes of unilateral wet AMD to study the conversion to wet AMD. Firstly, I evaluated longitudinally volume changes in inner and outer retinal layers of 71 eyes with early/intermediate AMD using optical coherence tomography (OCT). Our results showed that inner and outer retina layer volumes may differentiate AMD eyes from healthy eyes. When comparing those who progressed to wet AMD at year 2 to those who did not, we found that baseline volume of GCIPL may differentiate between the 2 groups. As it is an inner retinal change, I hypothesized that heritability of the retinal layers may influence the rate of retinal layer changes and that may in turn help understand the changes seen in aging and AMD. I worked with the TWIN Study database, in which OCT was done in eyes of twins of different age groups and OCT data were available on 364 eyes of 184 (92 pair) twins. I evaluated whether heritability was responsible for ageing changes of the retinal layers. I found that total retinal volume and inner retinal layer volumes may be affected by genetic factors

Management of neovascular age-related macular degeneration with ranibizumab: Long-term outcomes and second eye outcomes

Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are the established standard of care for neovascular age related macular degeneration (nAMD), however there are currently limited data on long-term outcomes of this therapy. Ranibizumab is one such anti-VEGF agent administered to treat nAMD. Patients diagnosed with nAMD undergo regular clinic based follow-up as part of their treatment, often on a monthly basis. Assessment during these appointments includes optical coherence tomography (OCT) scans, which can contribute to the detection of nAMD in the second eye. There is limited data on the symptomatic status, clinical presentation and outcomes of second eye nAMD whilst undergoing regular assessment for the first treatment eye under these conditions. Aims: The first aim of this thesis is to evaluate the long-term (5-year) outcomes of intravitreal ranibizumab (an anti-VEGF agent) in treating nAMD by examining a cohort within a real life clinic setting. The second aim is to compare the clinical presentation and treatment outcomes between the first and second treated eyes in patients that developed nAMD in both eyes, whilst under regular review for unilateral nAMD. Methods: A total of 208 patients (208 eyes) were included in a retrospective case series assessing the 5-year outcomes of nAMD treated with ranibizumab, entitled the long-term ranibizumab study (LTRS) (Chapter 3). Intervention was an individualised treatment model after three initial monthly loading doses. Visual acuity (VA), central macular thickness (CMT), qualitative OCT features, and adverse events (AE) were determined for each visit. Snellen VA was converted to Early Treatment Diabetic Retinopathy Study (ETDRS) letters for analysis. To assess outcomes of second eyes diagnosed with nAMD, a retrospective case series entitled second-eye ranibizumab study (SERS) forms the second part of this thesis (Chapter 4). Forty-five consecutive patients fulfilled the inclusion criteria of commencing treatment with ranibizumab in the first eye for nAMD between July 2007 and March 2011,and subsequently developing nAMD in the second eye with at least 12-months of follow-up in each eye. Treatment was administered under the same conditions as the LTRS. Snellen VA was measured, and OCT examination of both eyes at each visit assessed the presence of intra-retinal fluid (IRF) and sub-retinal fluid (SRF). Patient reported symptoms were recorded at every clinic visit. Paired t-tests were used to assess changes in VA and CMT over the study duration of the LTRS and SERS and two sample t- tests were used to evaluate VA differences between groups. Changes in VA compared to baseline were classified into the three categories: stable VA (loss or gain of ≤15 letters), improved VA (gain of >15 letters), or worse VA (loss of >15 letters). Linear regression was used to assess the effects of age, gender, number of injections, previous treatment, medical history, medications, and baseline VA on both VA and CMT changes. Chi-square test or Fisher’s exact test were used to measure proportions of patients with visual stability and OCT fluid free status at 12-months in the SERS. Results: In the LTRS, mean VA improved by 1.9 letters after 1 year (p=0.020) and decreased by 2.4 letters over 5-years of the treatment (p=0.040). At the end of year 5, 11.1% (23/208) of patients improved VA by more than 15 letters and 68.8% (143/208) of patients had stable VA, while 20.2% (42/208) patients lost more than 15 letters. Patients with VA less than 35 letters (approximate Snellen VA 6/60) at baseline showed significant VA improvement after 5-years of treatment (mean increase 11.5 letters, p=0.01), whilst those that were between 70 and 85 letters (approximate Snellen VA 6/12 to 6/6) at baseline showed a mean decrease (-12.9 letters, p=76 letters, or Snellen VA approximately 6/9)) showed greater stability of vision at 12-months vs. first treated eyes (p=0.05). There was no significant difference in mean VA change between first and second treated eyes. The proportion of OCT - fluid free eyes was higher amongst second treated eyes compared with first treated eyes at 12-months (70% vs. 40%, p=0.02). Intra-retinal fluid (IRF) was seen in 54% of second treated eyes at baseline compared with 84% in first treated eyes (p=0.01). Symptoms were absent in 54% of second treated eyes at baseline. The most common symptoms were “blurred vision” (28% of all patients) and metamorphopsia (11% of all patients). Conclusions: The visual gains achieved were not as significant as clinical trials, likely reflecting the differences in inclusion criteria of patients, and less rigorous follow-up and treatment. Intravitreal ranibizumab was effective in maintaining vision in patients with nAMD and reducing macula thickness over 5-years using an individualised treatment regime in a real-world setting.. Ranibizumab is a safe drug to use over 5-years in a real-world clinical setting. In patients undergoing treatment for nAMD in the first eye, OCT screening of the second eye at each visit may be necessary to detect second eye nAMD in this at-risk population. A large proportion of patients are asymptomatic at diagnosis of second eye disease, and a significant proportion of patients were detected to have treatable subfoveal nAMD with OCT alone. Second eye disease detected and treated by such a protocol showed a lower rate of IRF at baseline, suggesting early detection had occurred. Second eyes showed a higher rate of fluid free status at 12-months compared to the first treated eye, suggesting that early detection and treatment led to improved anatomical outcomes, potentially explaining superior VA outcomes. Patients commencing treatment in their second eye with good VA had better visual outcomes compared to those with worse VA