Optical Coherence Tomography-History, Evolution, and Future Prospects: 2023 Lasker-DeBakey Clinical Medical Research Award.

In this Viewpoint, 2023 Lasker-DeBakey Clinical Medical Research Award winners James G. Fujimoto, David Huang, and Eric A. Swanson discuss their invention­optical coherence tomography, which allows rapid detection of diseases of the retina that impair vision.

Simultaneous directional full-field OCT using path-length and carrier multiplexing.

Full-field swept-source optical coherence tomography (FF-SS-OCT) is an emerging technology with potential applications in ophthalmic imaging, microscopy, metrology, and other domains. Here we demonstrate a novel method of multiplexing FF-SS-OCT signals using carrier modulation (CM). The principle of CM could be used to inspect various properties of the scattered light, e.g. its spectrum, polarization, Doppler shift, or distribution in the pupil. The last of these will be explored in this work, where CM was used to acquire images passing through two different optical pupils. The two pupils contained semicircular optical windows with perpendicular orientations, with each window permitting measurement of scattering anisotropy in one dimension by inducing an optical delay between the images formed by the two halves of the pupil. Together, the two forms of multiplexing permit measurement of differential scattering anisotropy in the x and y dimensions simultaneously. To demonstrate the feasibility of this technique our carrier multiplexed directional FF-OCT (CM-D-FF-OCT) system was used to acquire images of a microlens array, human hair, onion skin and in vivo human retina. The results of these studies are presented and briefly discussed in the context of future development and application of this technique.

Artificial intelligence extension of the OSCAR-IB criteria.

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines.

Temporal patterns of visual recovery following pituitary tumor resection: A prospective cohort study.

Significant restoration of visual function can occur following pituitary tumor resection, although the time course of visual recovery remains poorly understood. This single-centre, two-year, prospective cohort study investigated the temporal patterns of visual recovery in consecutive patients undergoing pituitary tumor resection, between 2009 and 2018. Eyes were stratified based on pre-operative optical coherence tomography (OCT) retinal nerve fibre layer (RNFL) thickness measurements, with thin RNFL being defined as those within the fifth-percentile of age-matched normative values, and normal RNFL as those above the fifth-percentile. Visual function and OCT parameters were assessed pre-operatively, and at 6 weeks, 6 months, and 2 years post-operatively. 456 eyes of 228 patients (mean ± SD age, 53 ± 15 years) were included, of which 114 (25%) eyes had thin RNFL pre-operatively. Visual field recovery was observed in both groups during the first 6 weeks post-operatively (all Q ≤ 0.02), although improvements in visual field parameters between 6 weeks to 6 months were limited to eyes with thin RNFL (both Q < 0.05). No further improvements in visual function were detected beyond 6 months in both groups (both Q > 0.50). Similar trends were observed in linear regression analysis according to baseline visual function in both groups. In summary, eyes with normal RNFL thickness at baseline experienced most of their recovery within the first six weeks following surgery, while eyes with thin RNFL exhibited gradual improvements during the first six months. These findings have important implications when providing patient counselling and prognostication in the pre-operative setting.

Fluorescein angiography versus optical coherence tomography angiography: FA vs OCTA Italian Study.

PURPOSE: To assess the current role of fluorescein angiography after the introduction of optical coherence tomography angiography in real-life clinical practice. METHODS: This was a multicentric retrospective observational study to evaluate the number of fluorescein angiography and optical coherence tomography angiography procedures performed by different devices from January 2013 to December 2018. The centers involved were Centro Italiano Macula (Rome), and ophthalmology departments of University "G. D'Annunzio" Chieti-Pescara (Chieti) and "Azienda Ospedaliero Universitaria Careggi" (Florence). RESULTS: Out of 19,898 total fluorescein angiography procedures performed in the observation period, 3444 (17.3%) were in 2013, 3972 (19.9%) were in 2014, 3601 (18.1%) were in 2015, 3407 (17.2%) were in 2016, 3285 (16.5%) were in 2017, and 2189 (11%) were in 2018. Out of 7949 optical coherence tomography angiography procedures performed in the observation period, none were performed in 2013, 550 (6.9%) were in 2014, 908 (11.5%) were in 2015, 2098 (26.4%) were in 2016, 2090 (26.3%) were in 2017, and 2303 (28.9%) were in 2018. CONCLUSION: Fluorescein angiography procedures were performed less often after the introduction of optical coherence tomography angiography technology. The ease, speed, and safety of the optical coherence tomography angiography procedure in everyday clinical practice have facilitated more optical coherence tomography angiography application compared to fluorescein angiography in recent years. In the future, we will probably evaluate the different pathologies that still need an evaluation by fluorescein angiography.

Updates on ophthalmic imaging features of optic disc drusen, papilledema, and optic disc edema.

PURPOSE OF REVIEW: Optic nerve head elevation can be associated with vision loss. This review provides an update regarding key features of optic disc drusen (ODD) compared with papilledema from increased intracranial pressure and optic disc edema from other causes. RECENT FINDINGS: Clinical history and funduscopic examination are not sufficient to correctly diagnose different causes of optic nerve head elevation. Multimodal ophthalmic imaging is noninvasive and should be used as first-line diagnostic testing to distinguish optic disc edema or papilledema from pseudoedema. Advanced ophthalmic imaging, including enhanced depth imaging optical coherence tomography (EDI-OCT) and autofluorescence imaging, can visualize ODD at high resolution and determine whether there is optic disc edema. OCT angiography does not require contrast and can rapidly visualize papillary, peripapillary, and macular microvasculature and identify important vascular biomarker of ischemia and, potentially, visual prognosis. SUMMARY: Multimodal ophthalmic imaging can help in the diagnosis of ODD and optic disc edema and identify patients at high risk of vision loss and neurological issues in order to ensure appropriate diagnosis and treatment.

Advances in ophthalmic structural and functional measures in multiple sclerosis: do the potential ocular biomarkers meet the unmet needs?

PURPOSE OF REVIEW: Multiple sclerosis is a heterogeneous disorder. Biomarkers to monitor disease activities are highly desirable especially because of the recent shift toward personalized medicine that coincides with the expansion of disease-modifying therapy. The visual system is highly involved in multiple sclerosis, and the rapid advancement of ophthalmic techniques has boosted the development of potential ocular biomarkers for multiple sclerosis management. RECENT FINDINGS: Recent studies have found that the rapid thinning of the peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) occurs in the progressive stage. Furthermore, the inter-eye thickness difference of the GCIPL could be used in identifying unilateral optic neuritis to facilitate the early diagnosis of multiple sclerosis. Moreover, the retinal microvascular alterations measured as vessel density were found to be related to the disability and visual function, although a standardized protocol to measure retinal microvascular alterations has not been well established. Additionally, aberrant ocular motility, such as fixation microsaccades, can be used to measure disability objectively. SUMMARY: The fast expansion of potential ocular biomarkers measured as retinal microstructural, microvascular, and ocular motility changes may facilitate the diagnosis and management of multiple sclerosis.

Trends in optical coherence tomography angiography use in university clinic and private practice setting between 2014-2018.

BACKGROUND: The aim was to assess the trends in optical coherence tomography angiography (OCTA) use compared with fluorescein angiography (FA). METHODS: A bilateral patient's exam on a single day was considered one examination. A total of 3680 and 700 OCTA examinations and 3387 and 439 FA examinations were performed between 2014 and 2018 in a university clinic and private practice, respectively. A regression analysis was completed. RESULTS: The use of OCTA procedures grew 17-fold from 2015 till 2018. In a university clinic, ultrawide-field FA accounted for 2% of all FA examinations performed in 2015, and its use increased to 68% in 2018 while the number of narrow-field FA examinations dropped from 617 in 2014 to 220 in 2018. This decrease inversely correlated with the rise of diabetic retinopathy cases diagnosed with FA (R= -0.86, p= 0.02). In private practice, the increase in the use of OCTA was a primary driver of the decline of the FA use from 127 in 2015 to 27 in 2018, while the number of OCTA examinations was 344 in 2018 (R= -0.99, p= 0.06). CONCLUSION: The results of the study indicate that OCTA is a valuable tool capable of replacing FA in some selected cases.

Longitudinal Development of Peripapillary Hyper-Reflective Ovoid Masslike Structures Suggests a Novel Pathological Pathway in Multiple Sclerosis.

OBJECTIVE: Peripapillary hyper-reflective ovoid masslike structures (PHOMS) are a new spectral domain optical coherence tomography (OCT) finding. METHODS: This prospective, longitudinal study included patients (n = 212) with multiple sclerosis (MS; n = 418 eyes), 59 healthy controls (HCs; n = 117 eyes), and 267 non-MS disease controls (534 eyes). OCT and diffusion tensor imaging were used. RESULTS: There were no PHOMS in HC eyes (0/117, 0%). The prevalence of PHOMS was significantly higher in patients with MS (34/212, p = 0.001) and MS eyes (45/418, p = 0.0002) when compared to HCs (0/59, 0/117). The inter-rater agreement for PHOMS was 97.9% (kappa = 0.951). PHOMS were present in 16% of patients with relapsing-remitting, 16% of patients with progressive, and 12% of patients with secondary progressive disease course (2% of eyes). There was no relationship of PHOMS with age, disease duration, disease course, disability, or disease-modifying treatments. The fractional anisotropy of the optic radiations was lower in patients without PHOMS (0.814) when compared to patients with PHOMS (0.845, p = 0.03). The majority of PHOMS remained stable, but increase in size and de novo development of PHOMS were also observed. In non-MS disease controls, PHOMS were observed in intracranial hypertension (62%), optic disc drusen (47%), anomalous optic discs (44%), isolated optic neuritis (19%), and optic atrophy (12%). INTERPRETATION: These data suggest that PHOMS are a novel finding in MS pathology. Future research is needed to determine whether development of PHOMS in MS is due to intermittently raised intracranial pressure or an otherwise impaired "glymphatic" outflow from eye to brain. ANN NEUROL 2020;88:309-319.

[Progress of quantitative intravascular optical coherence tomography].

Intravascular optical coherence tomography (IVOCT) has emerged as a high-resolution and minimal-invasive imaging technique that provides high-speed visualization of coronary arterial vessel walls and clearly displays the vessel lumen and lesions under the intima. However, morphological gray-scale images cannot provide enough information about the tissue components to accurately characterize the plaque tissues including calcified, fibrous, lipidic and mixed plaques. Quantitative IVOCT ( qIVOCT) is necessary to provide the physiological contrast mechanisms and obtain the characteristic parameters of tissues with clinical diagnostic value. In this paper, the progress of qIVOCT is reviewed. The current methods for quantitatively measuring optical, elastic and hemodynamic parameters of vessel wall and plaque tissues using IVOCT gray-scale images and raw backscattered signals are introduced and potential development is forecast.

[Indications for fluorescein angiography and optical coherence tomography angiography (OCTA) in medical retina: Changes from 2015 and 2018]. / Indications d'angiographie à la fluorescéine et d'OCT-angiographie en consultation de rétine médicale : comparaison entre 2015 et 2018.

INTRODUCTION: Non-invasive multimodal imaging, including optical coherence tomography angiography (OCTA), has demonstrated high sensitivity and specificity for the management of retinal diseases. Since the availability of OCTA in 2015, we have developed a policy of "as little fluorescein angiography as possible". In this study, we describe the rate of OCTA and fluorescein angiography (FA) performed and their indications. METHODS: Retrospective descriptive single-centre study. Chart review of patients examined for retinal disorders by one medical retina specialist between January 2015 and June 2018. RESULTS: 3487 patients were examined for a retinal disease. The charts of 651 of these patients (1170 eyes) were randomly selected for analysis (study group). The mean age in the study group was 72 years (60% female). Overall, OCTA and FA were performed in 49.4% and 6.5% of the studied eyes respectively. After the first year, the rate of FA decreased to 2%. The main indications for OCTA were age-related macular degeneration (AMD): 50%, central serous chorioretinopathy (CSC): 12% and retinal vascular occlusion: 10%. The most frequent indications for FA were AMD: 49%, diabetic retinopathy (DR): 18% and CSC: 14%. FA was performed in 16%, 11% and 10% of eyes diagnosed with DR, CSC and AMD respectively (P<0.05). CONCLUSION: In routine practice, OCTA was performed in half of the eyes examined for a retinal disorder. The overall rate of FA was 6.5% and dropped to 2% after the first year of OCTA use. DR was the main disorder still requiring FA.

Trends and Outcomes of Intravascular Imaging-guided Percutaneous Coronary Intervention in the United States.

INTRODUCTION: Intravascular imaging-guided percutaneous coronary intervention (PCI) has shown to improve outcomes in randomized controlled trials. However, there are little real-world data about intravascular imaging utilization during PCI and its outcomes in the United States. METHODS: We conducted an observational analysis on the use of intravascular imaging (Intravascular Ultrasound or Optical Coherence Tomography)-guided PCI in 2,425,036 patients undergoing PCI between January 2010 and December 2014 from the Nationwide Inpatient Sample database. Utilizing propensity score matching, 83,988 matched pairs were identified. The primary outcome was in-hospital mortality. The secondary outcomes included cardiogenic shock and acute kidney injury. RESULTS: Among the 2,425,036 patients, 161,808 (6.7%) underwent imaging-guided PCI. Use of imaging-guidance increased from 6% in 2010 to 6.6% in 2014 (Ptrend < 0.001). The in-hospital mortality was significantly different between imaging-guided PCI and angiography-guided PCI [1.0% vs. 1.5%; adjusted OR: 0.67; 95% confidence interval (CI): 0.54-0.83, P < 0.001]. The rates of cardiogenic shock (2.5% vs. 3.1%; adjusted OR: 0.78; 95% CI: 0.66-0.93; P = 0.005) were significantly lower in imaging-guided PCI group and acute kidney injury rates (7.0% vs. 7.1%; adjusted OR: 0.99; 95% CI: 0.89-1.12; P = 0.919) were not significantly different. CONCLUSIONS: Imaging-guided PCI is associated with lower in-hospital mortality. Yet, a small proportion of patients undergoing PCI have imaging-guidance.

Intravascular ultrasound, optical coherence tomography, and fractional flow reserve use in acute myocardial infarction.

BACKGROUND: There are limited data on the use of intravascular ultrasound (IVUS), optical coherence tomography (OCT), and fractional flow reserve (FFR) during acute myocardial infarction (AMI). OBJECTIVES: To assess the temporal trends of IVUS, OCT, and FFR use in AMI. METHODS: A retrospective cohort study from the National Inpatient Sample (2004-2014) was designed to include AMI admissions that received coronary angiography. Administrative codes were used to identify percutaneous coronary intervention (PCI), IVUS, OCT, and FFR. Outcomes included temporal trends, inhospital mortality and resource utilization stratified by IVUS, OCT, or FFR use. RESULTS: In 4,419,973 AMI admissions, IVUS, OCT, and FFR were used in 2.6%, 0.1%, and 0.6%, respectively. There was a 22-fold, 118-fold, and 33-fold adjusted increase in IVUS, OCT, and FFR use, respectively, in 2014 compared to the first year of use. Non-ST-elevation AMI presentation, male sex, private insurance coverage, admission to a large urban hospital, and absence of cardiac arrest and cardiogenic shock were associated with higher IVUS, OCT, or FFR use. PCI was performed in 83.2% of the IVUS, OCT, or FFR cohort compared to 64.2% of the control group (p < .001). The cohort with IVUS/OCT/FFR use had lower inhospital mortality (adjusted odds ratio 0.53 [95% confidence interval 0.50-0.56]), more frequent discharges to home (83.7% vs. 76.8%), shorter hospital stays (4.3 ± 4.4 vs. 5.0 ± 5.5 days) and higher hospitalization costs ($90,683 ± 74,093 vs. $74,671 ± 75,841). CONCLUSIONS: In AMI, the use of IVUS, OCT, and FFR has increased during 2004-2014. Significant patient and hospital-level disparities exist in the use of these technologies.

Emerging techniques in atherosclerosis imaging.

Atherosclerosis is a chronic immunomodulated disease that affects multiple vascular beds and results in a significant worldwide disease burden. Conventional imaging modalities focus on the morphological features of atherosclerotic disease such as the degree of stenosis caused by a lesion. Modern CT, MR and positron emission tomography scanners have seen significant improvements in the rapidity of image acquisition and spatial resolution. This has increased the scope for the clinical application of these modalities. Multimodality imaging can improve cardiovascular risk prediction by informing on the constituency and metabolic processes within the vessel wall. Specific disease processes can be targeted using novel biological tracers and "smart" contrast agents. These approaches have the potential to inform clinicians of the metabolic state of atherosclerotic plaque. This review will provide an overview of current imaging techniques for the imaging of atherosclerosis and how various modalities can provide information that enhances the depiction of basic morphology.

Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS.

OBJECTIVE: To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity. METHODS: In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 months RESULTS: pRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs (p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged < 51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 µm; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 µm; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R2 0.36, p = 0.001). CONCLUSIONS: INL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to disease-modifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choice.

Trends in Retina Specialist Imaging Utilization from 2012 to 2016 in the United States Medicare Fee-for-Service Population.

PURPOSE: To characterize temporal trends and regional variance in retinal imaging utilization in the United States Medicare fee-for-service population from 2012-2016. DESIGN: Cross-sectional, retrospective database analysis. METHODS: This study addresses office or operating-room based retinal imaging. Our study population included retina specialists, defined as ophthalmologists performing either intravitreal anti-vascular endothelial growth factor injections or posterior segment laser photocoagulation and no neodymium-doped yttrium aluminum garnet laser capsulotomy. We recorded fundus photography, optical coherence tomography (OCT), intravenous fluorescein angiography (IVFA), indocyanine-green angiography, and ophthalmic ultrasound (B-scan) billed in the Medicare fee-for-service population from 2012-2016. Imaging obtained on any platform or device was eligible for inclusion (eg, posterior pole imaging vs ultrawidefield imaging). The main outcome measure was the relative utilization of retinal imaging modalities. RESULTS: National relative utilization of OCT increased from 61.5% in 2012 to 70.5% in 2016 (P < .001), while IVFA fell from 20.9% to 15.1% over the same interval (P < .001). Fundus photography decreased from 14.6% in 2012 to 11.7% in 2016 (P < .001). By 2016, the Midwest region had the highest relative utilization of OCT (75.2%) and lowest of IVFA (12.0%), while the West region had the lowest OCT (68.4%) and highest IVFA (17.0%). CONCLUSIONS: Among retina specialists, OCT usage increased while the utilization of fundus photography and IVFA has declined. The Midwest region had the highest utilization of OCT and lowest of IVFA.

Trends and outcomes of optical coherence tomography use: 877 patients single-center experience.

BACKGROUND: Optical-coherence-tomography (OCT) is an emerging invasive coronary imaging with still undefined clinical value. Recent data have underlined daily impact of such technique in several clinical settings such as acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) guidance. We aimed at assessing the trends and outcomes of OCT use in a high-volume percutaneous coronary interventions (PCI)-center. METHODS: Over 6 years, 1025 coronary artery segments in 877 patients underwent OCT evaluation. Clinical and procedural characteristics were prospectively collected. Clinical setting for OCT was: "Diagnostic OCT" (OCT for lesion evaluation after coronary angiography without further PCI); "PCI-guidance OCT" (OCT as a guidance for complex PCI, both by intention or after diagnostic OCT). Primary study end-point was the occurrence of target-vessel-failure (TVF) during the follow-up. RESULTS: Overall, OCT was successful in 99.1% of attempted lesions. Only one complication (coronary dissection requiring urgent PCI) occurred during OCT. After a follow-up of 695 ±â€¯562 days, TVF occurred in 8.2% of cases. Despite similar baseline characteristics, TVF-free survival curves were different in the two populations (5.4% after diagnostic OCT and 9.9% after PCI-guidance OCT). Minimal-lumen-area (MLA) of target lesion was independently associated with TVF (HR 0.7, 95% CI 0.6-0.8). This was mainly driven by a significant impact of MLA in patients not revascularized (HR 0.6, 95% CI 0.4-0.9). TVF did not change according to the study period despite the selection of patients with increasing complexity. CONCLUSIONS: OCT has a good safety profile across a broad spectrum of patients encountered in daily practice. The easy-to-assess MLA parameter may help stratify prognosis of patients undergoing OCT. These data call for further evaluations of OCT clinical impact. SUMMARY: OCT is a light-based imaging tool which had subvert the quite ordinary world of coronary imaging and the present study evaluates OCT use in a high-volume center. Our results suggest that application of OCT in "real world" patients presenting higher risk has a good safety profile. Several factors could predict a worse long-term outcome in patients undergoing OCT evaluation, mostly related to more complex clinical conditions. These findings could encourage even low-to intermediate volume centers to improve their OCT use in daily practice.

Future clinical applicability of optical coherence tomography angiography.

Optical coherence tomography angiography (OCT-A) is an emerging technology that allows for the non-invasive imaging of the ocular microvasculature. Despite the wealth of observations and numerous research studies illustrating the potential clinical uses of OCT-A, this technique is currently rarely used in routine clinical settings. In this review, technical and clinical aspects of OCT-A imaging are discussed, and the future clinical potential of OCT-A is considered. An understanding of the basic principles and limitations of OCT-A technology will better inform clinicians of its future potential in the diagnosis and management of ocular diseases.