Media MICE Pte Ltd, the parent company of PIE Magazine was the official media partner at the annual conference of the Vitreo Retinal Society of India held in Jaipur (VRSI 2018). The Retinal Imaging Symposium in the Hills of India (RISHI) was held prior to VRSI 2018. Below are some of the highlights from PIE Magazine’s coverage of the RISHI event.
OCT angiography: In search of the next ocular vital sign
“With improvements in interpretation software, OCTA could become one of the ocular vital signs,” said Dr. Glenn Jaffe.
Optical coherence tomography angiography (OCTA) is becoming an integral part of vitreoretinal examination. Dr. Glenn Jaffe from Duke University Eye Center in the United States provided critical insights into the applications of OCTA in both routine clinical and research setting. He noted: “When you consider the advantages and disadvantages of this technology, it really brings to life the utility of using it in the clinic and also highlights some of its unmet needs.”
OCTA has a lot of key advantages including its ability to see depth-resolved blood flow, show retinal vasculature and the absence of confounding leakage. In addition, OCTA is non-invasive and image acquisition is fast.
However, OCTA has peculiar disadvantages, which include its long interpretation time, absence of information on leakages (which could be useful in some situations), small field of view and presence of artifacts. Therefore, to overcome the disadvantages of OCTA, automatic algorithms and deep learning approaches have been deployed to speed up the interpretation time. In addition, integrated artifact removal software and faster scanning time have led to remarkable advancements in image quality and resolution, while image montaging has helped overcome the small field of view.
For vitreoretinal surgeons who are not fully familiar with OCTA, there is one important question: How would I use that technology in the clinic? “One can think of OCTA as a fluorescent angiogram that can be used when it helps with the diagnosis and monitoring,” advised Dr. Jaffe. “OCTA is particularly helpful for multimodal assessment,” he added.
Furthermore, Dr. Jaffe noted that artifact recognition is an important consideration of regular OCTA. These artifacts come in a variety of forms: shadowing, signal attenuation, segmentation artifacts and motion artifacts. In addition, false negative blood flows and projection artifacts are particularly associated with OCTA use. So, how can we recognize these myriad OCTA associated artifacts? The secret, according to Dr. Jaffe, lies in cross sectional scans with flow overlay, and he elegantly demonstrated this to the audience, using multimodal images from five clinical cases.
“In selected cases, the multimodal approach will allow the use of OCTA in the recognition of artifacts,” he concluded.
Dense B-scan OCTA, to the rescue in AMD-related type 3 neovascularization
“Dense B-scan OCTA can help show the implantation of Muller cell processes and vascular elements into the basal laminar deposits, which defines type 3 neovascularization and distinguishes it from other lesions with similar multimodal imaging features,” explained Dr. Bailey Freund.
About one-third of newly diagnosed Caucasian patients with neovascular AMD present with type 3 (intraretinal) neovascularization (NV), and these patients are at a high risk for bilateral involvement and atrophy. Currently, there is limited knowledge on the characterization of these type 3 NV lesions. However, dense B-scan OCT has emerged as a technique to get better quality structural B-scans with flow overlay.Dr. Bailey Freund from the New York University School of Medicine in the United States explained that the clinical findings of type 3 NV are intraretinal hemorrhage, hyperpigmentation, drusen and/or subretinal drusenoid deposits; while OCT findings are intraretinal fluid and intraretinal hyperreflective lesions. But how do these lesions appear on OCTA? Dr. Freund highlighted that type 3 NV lesions are visible in the mid retinal layers and are both fed and drained by retinal vessels. Particularly, he noted that these lesions do not contain retinochoroidal anastomoses.
Over the past few years, Dr. Freund and colleagues have evaluated the clinicopathological correlation of anti-vascular endothelial growth factor (anti-VEGF)-treated type 3 NV in AMD, and their findings are quite interesting. They showed that in these patients, the intraretinal complex was associated with the splitting of the retinal pigment epithelium and Muller cells’ deposition into the basal lamina, leading to adhesions. According to Dr. Freund, the identification of type 3 NV has significant connotations for monitoring patient outcomes, especially monitoring response to anti-VEGF treatment.
Understanding dome-shaped maculopathy
“As far as we know, serous retinal detachment associated with DSM is refractory to anti-VEGF; spironolactone reported to be successful in one case, and some cases may require no treatment,” said Dr. Adrian Koh.
Dome shaped maculopathy (DSM) is not a new entity. However, it has received little attention from retinal surgeons, according to Dr. Adrian Koh from Eye & Retina Surgeons, Camden Medical Centre in Singapore. There is no consensus among vitreoretinal surgeons concerning the best treatment of DSM. Several treatment modalities have been tried, such as anti-VEGF agents (i.e. aflibercept), spironolactone and micropulse laser therapy (MPLT), but with generally poor outcomes.
Dr. Shrinivas Joshi from M.M. Joshi Eye Institute, Hubballi, Karnataka, India, presented the case of a 66-year-old male myopic patient who presented with an eight-year history of diminution of vision in the left eye. Prior to presentation, he had been treated with a single dose of anti-VEGF, without improvement. Examination revealed a dome shaped macula and significant amounts of subretinal fluid. At one-month follow-up, the patient showed little or no improvement based on OCTA.
Further insights into the pathogenesis of DSM were provided by Dr. Koh. He summarized that currently, DSM is described as an inward convexity of the macula occurring in highly myopic eyes within the convexity of the posterior staphyloma. Dr. Koh stated that not all DSMs have the classic dome shaped configuration; therefore, radial scans are needed to detect them.
He added that several complications may arise from DSM, and of these, choroidal neovascularization is the most common, occurring in about 41 percent of patients. Other complications include diffuse chorioretinal atrophy, serous retinal detachment, macular hole and extrafoveal retinal schisis.
Dengue virus infection can cause DIIFOM of the fovea
“Intravitreal signs may show resolution, but resolution of ischemic damage may be incomplete even three months after dengue infection,” noted Dr. Vishali Gupta.
A new clinic-pathological syndrome of dengue maculopathy has been described and it’s called DIIFOM, which stands for Dengue-induced ischemic inflammatory foveolitis and outer maculopathy.
Dr. Vishali Gupta and colleagues at the Postgraduate Institute of Medical Education and Research (PGIMER) in Chandigarh, India, described dengue maculopathy in a cohort of 16 patients who were diagnosed based on positive dengue serology. General clinical features at presentation were consistent with dengue fever and anterior chamber inflammation was absent in all patients. Dr. Gupta noted that about 1 in 3 eyes showed superficial retinal hemorrhages in the macular area, while no evidence of retinitis was observed. The authors of this study went further to evaluate the macula using swept-source OCT and OCTA. They found foveolitis in 69 percent of eyes and all eyes showed edema of the outer plexiform layer and external limiting membrane (ELM) disruption.
At the three-month follow-up, Dr. Gupta and colleagues observed complete resolution of foveolitis and outer plexiform edema in all eyes. However, focal disruption of the ELM was persistent in about 20 percent of patients, and these patients continued to experience scotomas. In addition, persistent flow deficit in both superficial and deep plexuses were seen, which correlated with visual acuity. Two pathophysiological mechanisms were proposed by Dr. Gupta and colleagues: an ischemic and an inflammatory mechanism.
So, what will be the impact on outcomes to patients with dengue maculopathy? Dr. Gupta noted that while steroids can be used to control the ischemic component of DIIFOM, the outcome of ischemia following steroid therapy remains unknown.
Doing big things with big data in retinal diseases
“Big data is driving the machine learning revolution and is helping to validate it,” said Dr. Adnan Tufail.
According to a recent report from IBM, about 90 percent of the world’s information has been created in the last two years and we generate 2.5 quintillion bytes of data every day. There’s not enough space to fit all the zeros in that number! And this will only increase, as it’s estimated that 30 to 50 billion devices will be connected to the internet by 2020. Therefore, it’s important to understand how to use this data to address challenges in retinal disease diagnosis and treatment.
According to Dr. Adnan Tufail from Moorfields Eye Hospital in the United Kingdom (UK), big data could be useful in understanding the effectiveness of new treatments when introduced into real life populations, outside the tightly controlled environment of clinical trials. In settings like the UK, the availability of structured AMD data from electronic medical records was an opportunity to analyze outcomes of patients receiving anti-VEGF. Therefore, Dr. Tufail and colleagues, designed a study with the aim of providing real world outcome data, providing benchmarks for therapy and establishing predictive models. Following ethical approval, Dr. Tufail and colleagues had access to records of more than 11,000 wet AMD patients who received approximately 90,000 injections at 333,000 follow-up visits across 16 centers in the UK. Overall, the authors analyzed 2.8 million data items.
One key outcome of this study was that following anti-VEGF injections for AMD, visual acuity state – and not visual acuity change – was what patients found most meaningful.
It is an exciting field and there are many data useful data sources out there. Dr. Tufail explained recent attempts towards multimodal data sources like sensors, devices, internet searches, bio-banks and the linkage of these data sources. An example of this is the use of a new, home-based OCT, equipped with an artificial intelligence (AI) algorithm that interprets retinal images and sends a message to the patients’ physician.
So, can big data help reduce physician workload and cost of managing retinal diseases? Dr. Tufail described the RETMARKER and EYEART machine learning algorithms which have been used on more than 30,000 patients. “These algorithms have identified 100 percent of referable diseases and have saved costs of around 10 million GBP per year,” said Dr. Tufail. There is a plan to roll this out to all centers in the UK.
“A wealth of big, real world data is available to benchmark outcomes. In addition, big data can inform personalized medicine approach with the totality of the data,” concluded Dr. Tufail.
Counting what matters: Retinal biomarkers from OCT
“Quantifiable OCT biomarkers can help predict outcomes based on baseline characteristics, response to anti- VEGF and natural history,” said Dr. Faisal Beg.
Modern OCT imaging scanners provide high quality images of the human retina. However, pretty images aren’t enough. Retinal surgeons need quantifiable markers to classify disease, decide on optimal treatment strategies and monitor treatment response.
According to Dr. Faisal Beg, Professor, School of Engineering Science, Simon Fraser University, Canada, to be clinically useful and available for decision making in a timely manner, the whole process of quantification of retinal OCT images needs to be automated. He provided examples of critical OCT image parameters for which algorithms for quantification have been developed. These are measurements of retinal layer segmentation and thickness measurements, microvasculature segmentation and density, fluid segmentation and area measurements.
On the other hand, Dr. Koh provided an insight into the use of retinal biomarkers for disease prognostication. Biomarkers such as the length of retinal ellipsoid zone restoration have been used to assess response to anti-VEGF therapy and visual acuity in AMD.
Other retinal biomarkers, such as hyperreflective foci have been studied as quantifiable markers of retinal diseases, and according to Dr. Koh, are associated with poor outcomes in AMD and correlate with severity of diabetic maculopathy. Choroidal thickness decreases progressively with age and AMD patients have thinner choroids. Dr. Koh noted that baseline choroidal thinness is a negative prognostic factor for VA gains.
“OCT has become an indispensable diagnostic tool in modern ophthalmology and has facilitated the treatment of macular diseases with anti-VEGF agents. Today there is a paradigm shift towards specific morphological changes relevant for visual function, treatment outcomes and disease management,” Dr. Koh concluded.
AMD and masquerades: Don’t get fooled again
“Beware of these genetic dystrophies that can be misdiagnosed as AMD and CSCR and consider genetic testing to avoid unwarranted injections and laser therapy without a proper diagnosis,” noted Dr. David Sarraf.
Retinal surgeons need to be aware of diagnostic entities that can masquerade as AMD. These include geographic atrophy (GA), macular detachment, and others. Dr. David Sarraf from the Stein Eye Institute, University of California Los Angeles, United States, discussed several cases where retinal surgeons need to be on the lookout. “In one of our patients presenting with what appeared to be geographic RPE atrophy, further evaluation revealed that the patient had spinocerebellar ataxia 7,” he said.
In some cases, GA may be associated with a golden tapetal fundus. In this instance, think of a prgR mutation. In addition, a variety of other genetic mutations associated with cone rod dystrophy may present as geographic atrophy. “Watch out for Stargadt’s disease, in which there is complete loss of choriocapillary, so dark atrophy is seen with indocyanine green angiography (ICGA), whereas in AMD, there is incomplete loss, so you’ll see hyperfluorescent geographic atrophy on ICGA. On OCTA, there is fulminant loss of choriocapillary and intact surrounding areas in Stargadt’s, whereas it’s thin, with attenuated edges in AMD,” Dr. Sarraf warned.
“Best disease (vitelliform macular degeneration) is one of those rare diseases that can present with macular detachment and masquerade as AMD or central serous chorioretinopathy (CSCR),” explained Dr. Sarraf.
“There is associated retinal pigment epithelium channelopathy, leading to apical microvilli disruption. This can be further driven by thick choroids, especially in older patients causing fluid to accumulate in the subretinal space,” he said. Furthermore, Dr. Sarraf noted that in patients who are chronically unresponsive to currently available anti-VEGF and laser therapy, doctors should consider Best disease.
Are two retinas on the same person exactly the same? Assessing symmetry of the foveal avascular zone in OCTA
“No significant differences were observed between two eyes of the same subject using FAZ area, when corrected for axial length,” said Dr. Judy Kim.
When it comes to the eyes, it is generally assumed that two eyes are symmetric – and in many patients with retinal diseases, the contralateral eye is often used as the control. Therefore, it’s important to understand if indeed the two eyes in the same patient are truly symmetric. To answer this, Dr. Judy Kim and colleagues from the Medical College of Wisconsin looked at the foveal avascular zone (FAZ). There are many ways to quantify the FAZ. These include the area, the axis ratio, acircularity and the major horizontal axis. Dr. Kim and colleagues aimed to provide an answer to the question of symmetricity of the FAZ and the comparability of the various published FAZ metrics.
To do this, they studied data from 170 subjects with no known ocular or systemic diseases aged between 7 and 77 years. They imaged both eyes in each subject and measured axial lengths. Each image was segmented twice by the same observer to reduce segmentation errors and metric underwent multivariant component analysis.
What were the results of this interesting study? The authors found that the FAZ area captured individual differences in FAZ morphology. However, no significant differences observed between the two eyes on the same subject using FAZ area, when corrected for axial length. Therefore, Dr. Kim concluded that two eyes on the same subject are symmetric when assessed using the FAZ area.
Next, they evaluated the use of axis ratios, and found that there was no asymmetry in both eyes on the same subject due to the high degree of variation in the shape of the FAZ. Furthermore, Dr. Kim reported low overall variance in acircularity between eyes of the same subject.
“FAZ area seems to be the best measure of inter subject variability. More studies of combinations of FAZ metrics may be needed to identify most clinically relevant combinations,” she concluded.
