Jamie Reese

Intraoperative OCT Imaging of the Argus II Retinal Prosthesis System

BACKGROUND AND OBJECTIVE Optimal placement of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Sylmar, CA) is critical. Intraoperative optical coherence tomography (OCT) allows for intrasurgical visualization and confirmation of array placement. In this study, two different OCT systems were evaluated to assess the feasibility and utility of this technology during Argus II surgery. PATIENTS AND METHODS Intraoperative OCT was performed on five patients undergoing Argus II implantation at Cole Eye Institute from June 2015 to July 2016. The EnVisu portable OCT (Bioptigen, Morrisville, NC) and microscope-integrated RESCAN 700 (Zeiss, Oberkochen, Germany) intraoperative OCT systems were utilized. The EnVisu was used in three patients and the RESCAN 700 in three of the five patients. Following array tacking, intraoperative OCT was performed over the entire array including the edges and tack. RESULTS Intraoperative OCT allowed for visualization of the array/retina interface. Microscope integration of the OCT system facilitated ease of focusing, real-time feedback, surgeon-directed OCT scanning to the areas of interest, and enhanced image quality at points of interest. CONCLUSIONS Intraoperative imaging of the Argus II electrode array is feasible and provides information about electrode array-retina interface and distance to help guide a surgeon. Microscope integration of OCT appears to provide an optimal and efficient approach to intraoperative OCT during Argus II array placement. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:999-1003.].

OCT Angiography and Ellipsoid Zone Mapping of Macular Telangiectasia Type 2 From the AVATAR Study.

Purpose To evaluate alterations on optical coherence tomography angiography (OCT-A) and quantitatively assess alterations in the ellipsoid zone (EZ) in eyes with macular telangiectasia type 2 (MacTel type 2). Methods The Observational Assessment of Visualizing and Analyzing Vessels With Optical Coherence Tomography Angiography in Retinal Diseases study is an institutional review board-approved prospective, observational study investigating OCT-A in macular disease. Patients underwent spectral-domain (SD)-OCT and OCT-A imaging at a single visit. SD-OCT data were analyzed using a novel OCT EZ-mapping software to obtain linear, area, and volumetric measurements of the EZ-retinal pigment epithelium (RPE) complex across the macular cube. OCT-A retinal capillary density was measured using the Optovue Avanti split-spectrum amplitude-decorrelation angiography algorithm. EZ-RPE parameters were compared to age-matched, sex-matched controls. Results Fourteen eyes of seven patients (mean age, 59 ± 6.5 years) were analyzed. Mean visual acuity was 20/45 (range, 20/20–20/150). EZ-RPE central foveal mean thickness was 27.8 ± 6.7 μm, EZ-RPE central foveal thickness was 22.1 ± 21.6 μm, EZ-RPE central foveal area was 0.17 ± 0.04 mm2, and EZ-RPE central subfield volume was 0.017 ± 0.012 mm3. Each of these measurements was significantly inversely correlated with visual acuity (P < 0.02). In addition, all of these measurements were significantly reduced compared to controls (all P ≤ 0.005). OCT-A showed a reduced parafoveal vessel density of 50.8% temporally compared to 53.8% nasally (P = 0.01) in the superficial vascular plexus. In the deep vascular plexus, similar findings were noted with a parafoveal vessel density of 56.7% temporally and 58.8% nasally (P = 0.01). Conclusions Abnormalities in EZ-RPE thickness, area, and volume are correlated with visual acuity in MacTel type 2, and may provide quantitative markers to measure disease progression and treatment response. OCT-A was a useful adjunct for determining disease severity.

Intraoperative OCT-assisted Surgery for Proliferative Diabetic Retinopathy in the DISCOVER Study

Purpose To delineate the feasibility and role of intraoperative optical coherence tomography (iOCT) in surgical decision-making during vitreoretinal surgical interventions for proliferative diabetic retinopathy (PDR). Design Prospective, single-site, multi-surgeon consecutive case series. Participants Patients enrolled in the DISCOVER study who underwent vitreoretinal surgery for sequelae of PDR. Methods Subjects were identified from the first 2 years of the DISCOVER study that underwent vitreoretinal surgery for complications of PDR. Intraoperative imaging with a microscope-integrated iOCT system was performed at surgical milestones as determined by the surgeon. Data collected included clinical characteristics, image features, and survey-based surgeon feedback. Main Outcome Measures Main outcomes were 1) the percentage of cases with successful acquisition of iOCT (feasibility) and 2) the percentage of cases in which iOCT altered surgical decision-making (utility). Results Eighty-one eyes with PDR underwent vitreoretinal surgery in the DISCOVER study. Successful iOCT imaging was obtained for 80 of 81 eyes (98.8%). Of these, 36 (44.4%) were female and 44 (54.3%) were male. The surgeon preferred real-time feedback in 47 cases (58.6%), static review in 29 cases (36.3%), and was indeterminate in 4 cases (5%). Surgeons reported that in 2 cases (2.5%) the iOCT interfered with the surgery (e.g., microscope malfunction). In 41 of the 81 cases (50.6%), surgeons reported that iOCT provided valuable information (e.g., identification of dissection planes, identification of retinal hole). In addition, the iOCT data provided information that specifically altered the surgeons decision making (e.g., determination of peel completion, choice of tamponade) in 21 of 81 cases (26%). No adverse events were attributed to the iOCT system. Conclusions The results suggest that iOCT is feasible during complex vitreoretinal surgeries in patients with PDR using a microscope-integrated OCT platform. Utilizing intraoperative OCT, appears to frequently offer key information that may impact surgical decision-making and potentially patient outcomes.

Outcomes of Intraoperative OCT–Assisted Epiretinal Membrane Surgery from the PIONEER Study

Purpose To assess the retinal architecture changes which occur during epiretinal membrane (ERM) surgery, utilizing intraoperative optical coherence tomography (iOCT). Design Prospective multi-surgeon single center study. Subjects/Participants Subjects from the PIONEER iOCT study who underwent surgical intervention for management of ERM. Methods All subjects underwent vitrectomy with ERM peeling with optional internal limiting membrane (ILM) peeling. Preoperative, intraoperative, and postoperative quantitative and qualitative OCT assessments were performed. Clinical characteristics including visual acuity outcomes, central subfield thickness and complications including ERM recurrence and need for reoperation were assessed at 3, 6 and 12 months following surgery for membrane peeling, as available. Main Outcome measures Visual acuity outcomes, anatomic outcomes and complications including ERM recurrence. Microarchitectural alterations (i.e. retinal layer changes) following membrane peeling visualized with iOCT. Results Seventy-six were identified and included in this analysis of clinical outcomes and quantitative OCT assessment. Twenty-four eyes were excluded due to insufficient intraoperative OCT quality for quantitative assessment. The mean preoperative VA measured 20/63. The mean postoperative VA at 3 months was 20/41 (p<0.0001), at 6 months measured 20/36 (p < 0.0001), and at 12 months measured 20/33 (p < 0.0001). Preoperative mean central subfield thickness (CST) was 426 microns. At 3 months, the mean CST improved to 377 microns (p < 0.0001). The 6-month postoperative CST was 367 microns (p < 0.0001) and the 12-month postoperative CST measured 359 microns (p < 0.0001). Immediately following membrane peeling, the distance between the retinal pigment epithelium and the ellipsoid zone as well as the distance between the retinal pigment epithelium and the cone outer segment tips/interdigitation zone significantly increased (p < 0.001). iOCT identified occult residual membranes in 12% of cases and confirmed complete membrane peeling contrary to surgeon impression in 9% of cases. Reoperation was required for recurrent ERM in 1% of eyes. Conclusions iOCT-assisted ERM peeling resulted in significant improvement in visual acuity, reduction in macular thickness, and low recurrence rate. Additional research is needed with randomized clinical trials to better define the comparative success rates of image-guided ERM surgery to standard surgical visualization techniques.

The DISCOVER Study 3-Year Results: Feasibility and Usefulness of Microscope-Integrated Intraoperative OCT during Ophthalmic Surgery

PURPOSE To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. DESIGN Prospective, consecutive case series. PARTICIPANTS Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. METHODS The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. MAIN OUTCOME MEASURES Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. RESULTS Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%-98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%-49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%-33.0%). CONCLUSIONS The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

A Prospective Randomized Comparative Dosing Trial of Ranibizumab in Bevacizumab-Resistant Diabetic Macular Edema: The REACT Study

Purpose To assess the efficacy of ranibizumab for persistent diabetic macular edema (DME) previously treated with bevacizumab and compare monthly vs treat-and-extend (TAE) dosing. Design 12-month, open-label, prospective randomized comparative dosing study. Participants 27 participants with persistent foveal-involving DME recently treated with bevacizumab. Methods All subjects were to receive three initial monthly 0.3 mg ranibizumab injections before randomization to monthly (n=15) or TAE (n=12) injection protocols over 12 months. Treatment interval was extended by two weeks up to a maximum interval of 12 weeks in the TAE group if central subfield thickness (CST) was ≤ 300 μm or complete absence of intraretinal or subretinal fluid on the macular cube was observed. Follow-up interval was decreased by 2 weeks if CST increased above 300 μm with associated intraretinal and/or subretinal fluid. Main Outcome Measures Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), CST, adverse events. Results Prior to study enrollment, subjects received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by + 5.3 letters (p<0.05) and mean CST decreased by -99.6 μm (p<0.01) in all patients. At study exit, 18.5 % of subjects gained ≥ 3 lines of vision and 3.7% of subjects lost ≥ 3 lines. Patients treated via the TAE protocol gained +8.4 letters and decreased CST by -120.2 μm whereas those treated by monthly injection gained +2.7 letters and decreased CST by -83.1 μm at month 12. Conclusions Following conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab, significant functional and anatomic improvements were noted. Visual and anatomical outcomes were similar in TAE and monthly treatment protocols.

Assessment of inner and outer retinal layer metrics on the Cirrus HD-OCT Platform in normal eyes

Purpose Ellipsoid zone (EZ) and outer retinal integrity are strongly linked to visual prognosis, but quantitative normative data is lacking. This study evaluates the EZ, outer retina, and inner retina in eyes without macular disease across a wide age spectrum. Methods An IRB-approved study was performed for eyes without macular pathology undergoing Spectral Domain Optical Coherence Tomography (SD-OCT) scans on the Cirrus HD-OCT system (Carl Zeiss Meditec, Oberkochen, Germany). Scans were analyzed using a previously described automated EZ mapping tool with line-by-line manual verification. Segmentation included internal limiting membrane (ILM), outer nuclear layer/Henle fiber layer complex (ONL/HFL), EZ, and the retinal pigment epithelium (RPE). The output included metrics for the inner retina (ILM-OPL/HFL), outer retina (ONL/HFL-RPE), EZ-RPE area and volume, and en face EZ mapping. EZ-RPE attenuation on en face mapping was defined as EZ-RPE thickness < 20 um, and total attenuation was 0 um. Imaging parameters were assessed for the group and compared to age, sex, visual acuity and spherical equivalent. Results 167 eyes from 167 subjects were included. Mean age was 49.7 years (range 10–84 years). The mean foveal retinal thickness was 200.58 ± 19.22 um. Mean inner retinal thickness was 21.47 ± 13.60 um. Mean outer retinal thickness was 179.11 ± 18.52 um. Mean EZ-RPE thickness was 50.58 ± 6.01um. The mean EZ-RPE volume was 1.20 ± 0.10 mm3. Mean EZ attenuation percentage per macular map area was 0.87% ± 1.13% and mean percentage total attenuation was 0.12% ± 0.14%. Total and inner retinal thickness metrics decreased with age. Mean outer retinal thickness increased with age. EZ-RPE parameters were unchanged with age. However, EZ attenuation was negatively correlated with age. Conclusion This study provides important information for inner and outer retinal parameters. Future research on quantitative EZ integrity can utilize this data for comparison.

Optical Coherence Tomography Angiography in Eyes with Indeterminate Choroidal Neovascularization: Results from the AVATAR Study

Objective To evaluate the use of optical coherence tomography angiography (OCTA) to detect choroidal neovascularization (CNV) in eyes with indeterminate CNV features on conventional imaging. Design The AVATAR study is a prospective observational study of OCTA in patients undergoing routine spectral-domain optical coherence tomography (SD-OCT) for macular disease. Participants Subjects enrolled in the AVATAR study for which CNV was considered as part of a differential diagnosis based on clinical exam and/or prior imaging, but in whom the presence of CNV was not definitive on SD-OCT and fluorescein angiography (FA) imaging. interventions All patients were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA) and the Cirrus HD-OCT (Zeiss, Oberkochen, Germany) systems. Main Outcome Measures OCTA scans were assessed for the presence or absence of CNV. SD-OCT scans were assessed for the presence of fluid, hyperreflective material, serous pigment epithelial detachment (PED), shallow irregular PED, vitreomacular adhesion, epiretinal membrane, retinal pigment epithelium atrophy and central subfield retinal thickness. Univariate and multivariate logistic regression analyses were performed to identify features on SD-OCT associated with the presence of CNV on OCTA. Results Twenty-nine eyes of 29 patients met the criteria for inclusion. A CNV lesion was detected on OCTA in 8 (28%) eyes; 21 (72%) eyes were negative for CNV. After adjusted for age, gender and central subfield retinal thickness, the presence of shallow irregular PED [odds ratio, 148; 95% confidence interval, 3.22-6830; p = 0.011], as well as the combinations of intraretinal fluid and sub-retinal pigment epithelium material [odds ratio, 16.8; 95% confidence interval, 1.43-198; p = 0.025] on SD-OCT were significantly associated with the presence of CNV on OCTA. Conclusions OCTA enabled the identification of CNV that was otherwise indeterminate with prior imaging in select eyes. The presence of a shallow irregular PED as well as intraretinal fluid combined with sub-retinal pigment epithelium material were both associated with the presence of CNV. OCTA may be a valuable adjunct to conventional SD-OCT and FA imaging in the detection and surveillance of CNV, particularly in diagnostic dilemmas.

Comparison of OCT Angiography Review Strategies to Identify Vascular Abnormalities in the AVATAR Study

Purpose To compare review strategies for optical coherence tomography angiography (OCT-A) for multiple disease features found in common diseases of the choroid and retina. Design Prospective, observational study. Participants Patients with macular disease undergoing routine spectral-domain optical coherence tomography (SDOCT). Methods Eyes were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA), and the split-spectrum amplitude decorrelation angiography (SSADA) algorithm software was utilized for OCT-A performance. Scans were reviewed by 2 masked expert reviewers. A third masked reviewer was utilized in cases of reviewer disagreement. A single report using automated segmentation within the Avanti software to represent the superficial retina capillary plexus, deep retina capillary plexus, outer retina, and choroid capillary layer was generated. A continuous slab descent video export was also reviewed for each OCT-A scan. This video consisted of a continuous (e.g., line-by-line) review of the en face OCT- data. Each dataset was reviewed for the presence of three pathologic features: choroidal neovascularization, microaneurysms, and macular ischemia. Main Outcome Measures Comparison of identification rates of retinal and choroidal microvascular abnormalities using different review strategies. Results Four hundred twenty-one eyes were included in the study. Of those, 350 eyes had reports that were deemed sufficient quality for interpretation and analysis by both reviewers. Identification rates of choroidal neovascularization, microaneurysms, and macular ischemia on the report were 90.5%, 84.5%, and 95.4% respectively compared to the overall presence. Likewise, rates of identification in the continuous slab descent review video were 88.1%, 96.4%, and 95.4% for choroidal neovascularization, microaneurysms, and macular ischemia respectively compared to the overall presence. Cohens kappa values ranged from 0.80 to 0.96, corresponding to very good agreement between the report and continuous slab descent review for each variable. Conclusions Defining an optimal reporting strategy for OCT-A is important for diagnostic accuracy and optimizing workflow in retina clinics. In this study, OCT-A report using automated segmentation was comparable to continuous slab descent review for identifying microvascular abnormalities of the retina and choroid.