Response to 1-Year Fixed-Regimen Bevacizumab Therapy in Treatment-Naïve DME Patients: Assessment by OCT Angiography.

PURPOSE: To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using optical coherence tomography angiography (OCT-A). METHODS: This prospective study was performed in patients with treatment-naïve DME. The eyes of patients were imaged using a swept-source OCT system with a scan area of 6 × 6 mm. The DME patients with a central macular thickness (CMT) of ≥300 µm received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA), CMT, microaneurysm (MA) count, and foveal avascular zone (FAZ) area in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as vessel density in SCP, were assessed in the patients. In addition, the response (good or poor) of the DME eyes to bevacizumab treatment and the final visual acuity (BCVA of 75 letters) were analyzed. RESULTS: Seventy-seven eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 425.06 µm (±77.15) to 350.25 µm (±82.04) and improved BCVA by about 8.61 letters (from 64.73 to 73.34) in the patients. The mean number of MAs in SCP decreased from 3.51 ± 2.07 to 2.31 ± 1.15 (p < 0.001) and in DCP from 17.12 ± 11.56 to 12.21 ± 6.99 (p < 0.001), whereas the area of FAZ increased in SCP from 328.22 ± 131.38 to 399.70 ± 156.98 (p < 0.001) and in DCP from 571.13 ± 396.01 to 665.89 ± 412.77 (p = 0.001). The final BCVA letter score and CMT were statistically significant in both poor and good responders, as well as in BCVA < 75 and BCVA ≥ 75 groups. CONCLUSION: The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. Apart from noninvasive visualization of microvascular damage, OCT-A showed limited usefulness in predicting treatment response. Although the study showed that the number of MAs was significantly reduced during treatment, which is an OCT-A predictor of a good response to bevacizumab treatment at a 12-month visit, commonly observed artifacts may reduce the usefulness of OCT-A.

Updates on the utility of anterior segment optical coherence tomography in the assessment of filtration blebs after glaucoma surgery.

The formation of filtration blebs is the main drainage mechanism for reducing intraocular pressure after traditional incisional glaucoma surgery such as trabeculectomy and non-penetrating deep sclerotomy. Early and short-lasting blebs may also occur after canaloplasty. Bleb formation also plays an important role after the implantation of glaucoma drainage devices, including Minimally Invasive Glaucoma Surgery devices. Anterior segment optical coherence tomography (AS-OCT) is a rapid and non-invasive high-resolution imaging technique that has evolved in recent years to become a routine examination. Anterior segment optical coherence tomography (AS-OCT) provides key information in the assessment and follow-up of glaucoma surgery, especially in the assessment of filtration blebs. Thus, bleb morphology can be qualitatively classified into diffuse, cystic, encapsulated and flattened, and AS-OCT imaging can also provide several quantitative parameters of the bleb, such as total bleb height, bleb fluid-filled cavity height, bleb wall thickness, number of microcysts and trabeculectomy opening size. These parameters could have an impact on clinical management during follow-up because they may predict the success or failure of the surgery in the early and late postoperative periods. Additionally, they may also guide the procedures used to increase filtration and reduce intraocular pressure, such as bleb needling and laser suture lysis.

Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound.

OBJECTIVES: We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. METHODS: A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. RESULTS: Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. CONCLUSION: Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

Treatment of In-Stent Restenosis by Excimer Laser Coronary Atherectomy and Drug-Coated Balloon: Serial Assessment with Optical Coherence Tomography.

OBJECTIVES: We aimed to compare the results of neointimal modification before drug-coated balloon (DCB) treatment with excimer laser coronary atherectomy (ELCA) plus scoring balloon predilation versus scoring balloon alone in patients presenting with in-stent restenosis (ISR). BACKGROUND: Treatment of ISR with ELCA typically results in superior acute gain by neointima debulking. However, the efficacy of combination therapy of ELCA and DCB remains unknown. METHODS: A total of 42 patients (44 ISR lesions) undergoing DCB treatment with ELCA plus scoring balloon (ELCA group, n = 18) or scoring balloon alone (non-ELCA group, n = 24) were evaluated via serial assessment by optical coherence tomography (OCT) performed before, after intervention, and at 6 months. RESULTS: Although there was significantly greater frequency of diffuse restenosis and percent diameter stenosis (%DS) after intervention in the ELCA group, comparable result was shown in %DS, late lumen loss, and binary angiographic restenosis at follow-up. On OCT analysis, a decreased tendency in the minimum lumen area and a significant decrease in the minimum stent area were observed in the ELCA group between 6-month follow-up and after intervention (-0.89 ± 1.36 mm2 vs. -0.09 ± 1.25 mm2, p = 0.05, -0.49 ± 1.48 mm2 vs. 0.28 ± 0.78 mm2, p = 0.03, respectively). The changes in the neointimal area were similar between the groups, and target lesion revascularization showed comparable rates at 1 year (11.1% vs. 11.4%, p = 0.85). CONCLUSIONS: Despite greater %DS after intervention, ELCA before DCB had possible benefit for late angiographic and clinical outcome.

Scleral lens fitting and assessment strategies.

PURPOSE: To describe prescriber reported scleral lens fitting and assessment strategies. METHODS: The SCOPE (Scleral Lenses in Current Ophthalmic Practice Evaluation) study group designed and administered an IRB approved, electronic survey (REDCap) regarding current scleral lens fitting and assessment methods. The survey was distributed to attendees of the 2017 Global Specialty Lens Symposium. RESULTS: 95 practitioners responded to the survey. Over half of the respondents, 58% (55/95) reported fitting scleral lenses for less than five years (new prescribers), and 42% (40/95) reported fitting scleral lenses for more than five years (experienced prescribers). There was a statistically significant difference between their initial use of technology (χ2 = 21.117, p < 0.0005) in selection of a diagnostic lens. New prescribers consider base curve first (60%, 33/55), while experienced prescribers considered sagittal depth first (63%, 25/40) in their initial scleral lens selection. All of the experienced lens prescribers (100%, 39/39) reported estimating central clearance by comparing thickness of the post-lens tear reservoir to scleral lens thickness using a slit lamp beam at least some of the time, and 62% of new scleral lens prescribers (34/55; χ2 = 19.175, p < 0.0005) reported doing so. All (100%, 40/40) experienced prescribers schedule scleral lens follow-ups at a specific time and assess conjunctival compression (100%, 40/40), conjunctival staining (100%, 39/39), and corneal staining (100%,40/40) after lens removal. CONCLUSIONS: Practitioners with varying backgrounds and experience have added sclerals to their lens inventories. However, definite guidelines for fitting have not been developed. The results of a survey are provided; demonstrating that among practitioners with greater than 5 years of scleral lens experience, a consensus has emerged for best practices. Strategies for lens evaluation, which may inform future efforts at generating scleral fitting standards are described.

Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking.

A Review of the Clinical Utility of Intravascular Ultrasound and Optical Coherence Tomography in the Assessment and Treatment of Coronary Artery Disease.

Coronary artery disease remains one of the leading causes of morbidity and mortality in the United States. As a medical society, we continue to search for ways to better treat coronary artery disease and prevent acute coronary syndrome (ACS). As it stands, only statins and antiplatelet agents have been proven to significantly reduce the occurrence of ACS. A histopathological understanding of the pathogenesis of ACS has provided insight into the importance of plaque morphology. Therefore, it has been proposed that increasing the ability to detect true vulnerable, "at-risk" lesions, would foster the use of percutaneous coronary intervention as a means for the prevention of ACS. There are now several different imaging modalities to help cardiologists stratify plaque stability. These include, but are not limited to, angioscopy, magnetic resonance angiography, intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared fluorescence. To date, the most studied and frequently used in clinical trials are IVUS and OCT. Following a brief background discussion of IVUS and OCT, we will objectively evaluate each modality's ability to detect specific morphological characteristics. This article will also discuss IVUS and OCT's clinical utility with regard to proper stent placement and follow-up after percutaneous coronary interventions.

Speckle statistics in OCT images: Monte Carlo simulations and experimental studies.

The speckle pattern of an optical coherence tomography (OCT) image carries potentially useful sample information that may assist in tissue characterization. Recent biomedical results in vivo indicate that the distribution of signal intensities within an OCT tissue image is well described by a log-normal-like (Gamma) function. To fully understand and exploit this finding, an OCT Monte Carlo model that accounts for speckle effects was developed. The resultant Monte Carlo speckle statistics predictions agree well with experimental OCT results from a series of control phantoms with variable scattering properties; the Gamma distribution provides a good fit to the theoretical and experimental results. The ability to quantify subresolution tissue features via OCT speckle analysis may prove useful in diagnostic photomedicine.

Assessment of the effects of ultrasound-mediated glucose on permeability of normal, benign, and cancerous human lung tissues with the Fourier-domain optical coherence tomography.

The objective of this study was to evaluate the effects of ultrasound-mediated analyte diffusion on permeability of normal, benign, and cancerous human lung tissue in vitro and to find more effective sonophoretic (SP) delivery in combination with the optical clearing agents (OCAs) method to distinguish normal and diseased lung tissues. The permeability coefficients of SP in combination with OCAs diffusion in lung tissue were measured with Fourier-domain optical coherence tomography (FD-OCT). 30% glucose and SP with a frequency of 1 MHz and an intensity of 0.80 W/cm2 over a 3 cm probe was simultaneously applied for 15 min. Experimental results show that the mean permeability coefficients of 30% glucose/SP were found to be (2.01±0.21)×10(-5) cm/s from normal lung (NL) tissue, (2.75±0.28)×10(-5) cm/s from lung benign granulomatosis (LBG) tissue, (4.53±0.49)×10(-5) cm/s from lung adenocarcinoma tumor (LAT) tissue, and (5.81±0.62)×10(-5) cm/s from lung squamous cell carcinoma (LSCC) tissue, respectively. The permeability coefficients of 30% glucose/SP increase approximately 36.8%, 125.4%, and 189.1% for the LBG, LAT, and LSCC tissue compared with that for the NL tissue, respectively. There were statistically significant differences in permeability coefficients of 30% glucose/SP between LBG and NL tissue (p<0.05), between LAT and NL tissue (p<0.05), and between LSCC and NL tissue (p<0.05). The results suggest that the OCT functional imaging technique to combine an ultrasound-OCAs combination method could become a powerful tool in early diagnosis and monitoring of changed microstructure of pathologic human lung tissue.

The OSCAR-IB consensus criteria for retinal OCT quality assessment.

BACKGROUND: Retinal optical coherence tomography (OCT) is an imaging biomarker for neurodegeneration in multiple sclerosis (MS). In order to become validated as an outcome measure in multicenter studies, reliable quality control (QC) criteria with high inter-rater agreement are required. METHODS/PRINCIPAL FINDINGS: A prospective multicentre study on developing consensus QC criteria for retinal OCT in MS: (1) a literature review on OCT QC criteria; (2) application of these QC criteria to a training set of 101 retinal OCT scans from patients with MS; (3) kappa statistics for inter-rater agreement; (4) identification reasons for inter-rater disagreement; (5) development of new consensus QC criteria; (6) testing of the new QC criteria on the training set and (7) prospective validation on a new set of 159 OCT scans from patients with MS. The inter-rater agreement for acceptable scans among OCT readers (n = 3) was moderate (kappa 0·45) based on the non-validated QC criteria which were entirely based on the ophthalmological literature. A new set of QC criteria was developed based on recognition of: (O) obvious problems, (S) poor signal strength, (C) centration of scan, (A) algorithm failure, (R) retinal pathology other than MS related, (I) illumination and (B) beam placement. Adhering to these OSCAR-IB QC criteria increased the inter-rater agreement to kappa from moderate to substantial (0.61 training set and 0.61 prospective validation). CONCLUSIONS: This study presents the first validated consensus QC criteria for retinal OCT reading in MS. The high inter-rater agreement suggests the OSCAR-IB QC criteria to be considered in the context of multicentre studies and trials in MS.

Reproducibility of cornea measurements in anterior segment OCT images of normal eyes and eyes with bullous keratopathy analyzed with the Zhongshan Assessment Program.

PURPOSE: To determine the interobserver and intraobserver measurement reproducibility of cornea parameters of both normal eyes and eyes with bullous keratopathy (BK) obtained with the Zhongshan Assessment Program (ZAP) on anterior segment optical coherence tomography (AS-OCT) images. METHODS: A comparative study was carried out on 24 healthy volunteers and 25 subjects with BK. AS-OCT images were independently analyzed by two examiners. Parameters examined: anterior chamber depth (ACD), central corneal thickness (CCT), posterior corneal curvature (PCC), and posterior corneal arc length (PCAL). Interobserver and intraobserver reproducibility of these parameters was calculated in terms of limits of agreement (mean of differences ± 1.96SD of differences). RESULTS: In the normal group, both horizontal and vertical ACD were successfully measured in 23 of 24 (96%) images. The mean bias for two measurements by two different observers ranged from 0.003 to 0.117 mm for ACD, PCC, and PCAL measurements and from 0.013 to 2.25 µm for CCT measurements, and there were no differences between the two observers (P > 0.05). Mean bias for two measurements by the same grader ranged from 0.005 to 0.327 mm for ACD, PCC, and PCAL measurements and 1.46 to 2.53 µm for CCT measurements. There was no difference between the two observations (P > 0.05). Similar results were found in the BK group. CONCLUSIONS: There was high inter- and intraobserver reproducibility for normal and pathologic corneas using the ZAP software. The ZAP software may serve as a new investigatory tool for accurately evaluating the anterior segment and corneal parameters for corneal procedures.

Characteristics and reproducibility of anterior chamber angle assessment by anterior-segment optical coherence tomography.

PURPOSE: To evaluate the basic characteristics and reproducibility of anterior chamber angle (ACA) measurements determined by anterior-segment optical coherence tomography (AS-OCT) in open-angle and primary angle closure suspect (PACS) patients. METHODS: Thirty-nine open-angle and 18 PACS patients were imaged for ACA by AS-OCT. Subjects underwent imaging of the nasal, temporal and inferior ACA under conditions of constant light, and darkness. For analysis, we used three ACA parameters handled by the Visante OCT software: angle opening distance at 500 µm (AOD(500)), trabecular-iris space area at 500 µm (TISA(500)) and angle recess area at 500 µm (ARA(500)). For determination of inter-session reproducibility, a single well-trained operator (D.Y.K.) scanned all patients at two different visits. For determination of inter-operator variability, a second operator (S.B.P.) acquired another set of images independently. Three sets of images were acquired at least 24 hour apart. RESULTS: All parameters were significantly different when measured both in light and darkness, and in the nasal and temporal quadrants. There were no significant differences between the left and right eyes in the three ACA parameters in all quadrants. The temporal angle was wider than the nasal and inferior angles. All parameters of the nasal, temporal angles had excellent inter-session and inter-operator reproducibility [intra-class correlation coefficient (ICC) 0.796-0.981], but these values were slightly lower for inferior angle measurements (ICC 0.662-0.892) in both open-angle and PACS groups. CONCLUSION: AS-OCT provides quantitative and reproducible assessment of ACA. Reproducibility was lower in the inferior angle compared with the nasal and temporal angles, perhaps because of variable placement of the scleral spur.

OCT technology development: where are we now? A commercial perspective.

The field of optical coherence tomography (OCT) has grown enormously since its inception in 1991 at MIT, encompassing many areas of imaging research. Improvements in the optical technology used in OCT systems, and in the design of the OCT interferometers and probes, has resulted in steadily improving image quality and more practical probe designs. Successful commercial application of OCT occurred first in retina imaging, and many further applications now appear ripe for translation from the laboratory to the marketplace. In this paper, I review this translation process from a commercial perspective, and attempt to draw helpful conclusions.

The use of intra-coronary optical coherence tomography for the assessment of sirolimus-eluting stent fracture.

Drug-eluting stents (DES) have made a tremendous impact on the practice of percutaneous coronary intervention. Recently however, long-term DES failures have become a focal point, particularly with restenosis and thrombosis. An uncommon, yet important cause of DES failure is stent fracture. Of the two established first generation DES, the sirolimus-eluting stent (SES) has been particularly linked to cases of stent fracture, likely as a result of its closed cell design compared with other DES employing an open cell system. We present 2 cases of SES fracture confirmed using high-resolution intravascular optical coherence tomography giving unique insights into the in-vivo appearance of this complication.

Resource use and costs associated with diabetic macular edema in elderly persons.

OBJECTIVE: To examine trends in resource use and the effect of incident diabetic macular edema (DME) on 1- and 3-year total direct medical costs in elderly patients. METHODS: We used a nationally representative 5% sample of Medicare beneficiaries from 2000 through 2004 to identify patients with incident DME and a control cohort of patients with diabetes mellitus but no history of retinal disease. We summed Medicare reimbursement amounts for all claims and applied generalized linear models to estimate the effect of DME on 1- and 3-year costs. We also examined the use of select imaging techniques and treatments. RESULTS: After adjusting for demographic characteristics and baseline comorbid conditions, DME was associated with 31% higher 1-year costs and 29% higher 3-year costs. There were significant shifts in the use of testing and treatment modalities. From 2000 to 2004, use of intravitreal injection increased from 1% to 13% of patients; use of optical coherence tomography increased from 2.5% to more than 40%. Use of laser photocoagulation decreased over time. CONCLUSIONS: After adjusting for demographic variables and baseline comorbid conditions, new-onset DME was a significant independent predictor of total medical costs after 1 and 3 years. Diagnostic and treatment modalities used for DME have changed significantly.