Optical coherence tomography angiography: a non-invasive tool to image end-arterial system

Optical coherence tomography angiography (OCTA) is a relatively novel technology for in vivo imaging of vascular network. It uses moving erythrocytes as contrasting mechanism and avoids the use of intravenous dyes. A depth-resolved 3-dimensional image set can be generated within seconds using the technique of OCTA. Therefore, it possesses a great potential for widespread application in ophthalmic angiography. Herein we discuss the most common technologies behind OCTA and the scope of future technical improvement. We provide a perspective on advantages and disadvantages of OCTA over conventional fluorescein angiography and indocyanine green angiography. Lastly, current literature on the clinical application of OCTA in common ocular diseases including neovascular age-related macular degeneration, diabetic retinopathy, retinal artery and vein occlusion, and glaucoma are reviewed

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

Biomarkers in Early Response to Brolucizumab on Pigment Epithelium Detachment Associated with Exudative Age-Related Macular Degeneration.

The purpose of this study was to describe early changes in the morphology of pigment epithelium detachments (PED) after an intravitreal injection of Brolucizumab into eyes with macular neovascularization secondary to exudative age-related macular degeneration (e-AMD). We included twelve eyes of 12 patients with PED secondary to e-AMD which were not responding to prior anti-VEGF treatments. An ophthalmic examination and an assessment of PED-horizontal maximal diameter (PED-HMD), PED-maximum high (PED-MH) and macular neovascularization (MNV) flow area (MNV-FA) by the means of structural optical coherence tomography (OCT) and OCT Angiography (OCT-A) were performed at baseline, as well as 1, 7, 14 and 30 days after the injection. The mean age of the population of study was 78.4 (SD ± 4.8). The mean number of previous Ranibizumab or Aflibercept injections was 13 (SD ± 8). At the last follow-up visit, the PED-HMD did not significantly change (p = 0.16; F(DF:1.94, 20,85) = 1.9), the PED-MH showed a significant reduction [p = 0.01; F(DF:1.31, 14.13) = 6.84.] and the MNV-FA did not significantly differ (p = 0.1; F(1.97, 21.67) = 2.54) from baseline. No signs of ocular inflammation were observed during follow-up. A single Brolucizumab injection was able to determine the short-term effects on PEDs' anatomical features of eyes with an unresponsive e-AMD

Sequential Morphological Changes in the CNV Net after Intravitreal Anti-VEGF Evaluated with OCT Angiography

PURPOSE: To assess and describe sequential morphological changes in the choroidal neovascularization (CNV) net using optical coherence tomography angiography (OCTA) in patients undergoing treatment with intravitreal antivascular endothelial growth factor (VEGF). METHODS: Prospective cohort study. OCTA was performed sequentially: before (t0), 1 h (t1), 1 week (t2) and 1 month after the injection (t3), using Avanti RTVue XR equipped with the AngioVue® software (Optovue, Calif., USA). All images were classified by two independent graders. RESULTS: Ten eyes of 10 patients, with a mean age of 72.4 ± 10.5 years, were included. CNV morphology was described as tree-like in 5 eyes, glomerular in 1 and fragmented in 4. A fibrovascular capsule surrounding the CNV net was found in 4 eyes and a feeder trunk was noticed in 6. No changes were observed at t1. Loss of peripheral capillaries, vessel fragmentation and decreased vessel density were evident in 8 eyes at t2. The CNV capillary density and the peripheral anastomosis increased in all of these at t3. Two eyes remained unchanged through the whole length of follow-up. CONCLUSIONS: Significant changes in the CNV net can be observable in OCTA at least 1 week after intravitreal anti-VEGF. The safety of frequent examinations may provide a method of gauging treatment effects

Indocyanine Green Angiography and Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration

To compare the capability of indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in detecting choroidal neovascularization (CNV)

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