Publications by authors named "Jamie Reese"

41 Publications

Risk Classification for Progression to Subfoveal Geographic Atrophy in Dry Age-Related Macular Degeneration Using Machine Learning-Enabled Outer Retinal Feature Extraction.

Ophthalmic Surg Lasers Imaging Retina 2022 Jan 1;53(1):31-39. Epub 2022 Jan 1.

Background And Objective: To evaluate the utility of spectral-domain optical coherence tomography biomarkers to predict the development of subfoveal geographic atrophy (sfGA).

Patients And Methods: This was a retrospective cohort analysis including 137 individuals with dry age-related macular degeneration without sfGA with 5 years of follow-up. Multiple spectral-domain optical coherence tomography quantitative metrics were generated, including ellipsoid zone (EZ) integrity and subretinal pigment epithelium (sub-RPE) compartment features.

Results: Reduced mean EZ-RPE central subfield thickness and increased sub-RPE compartment thickness were significantly different between sfGA convertors and nonconvertors at baseline in both 2-year and 5-year sfGA risk assessment. Longitudinal change assessment showed a significantly higher degradation of EZ integrity in sfGA convertors. The predictive performance of a machine learning classification model based on 5-year and 2-year risk conversion to sfGA demonstrated an area under the receiver operating characteristic curve of 0.92 ± 0.06 and 0.96 ± 0.04, respectively.

Conclusions: Quantitative outer retinal and sub-RPE feature assessment using a machine learning-enabled retinal segmentation platform provides multiple parameters that are associated with progression to sfGA. .
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http://dx.doi.org/10.3928/23258160-20211210-01DOI Listing
January 2022

The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept.

J Pers Med 2021 Nov 1;11(11). Epub 2021 Nov 1.

Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44106, USA.

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline ( = 0.03) but increased by 59% from Year 1 ( = 0.04). Arm 2 decreased by 61% from Baseline ( = 0.008) and by 31% from Year 1 ( = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; < 0.001; 776 to 207; < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.
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http://dx.doi.org/10.3390/jpm11111126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619795PMC
November 2021

Vitreomacular Traction Surgery from the DISCOVER Study: Intraoperative OCT Utility, Ellipsoid Zone Dynamics, and Outcomes.

Ophthalmic Surg Lasers Imaging Retina 2021 10 1;52(10):544-550. Epub 2021 Oct 1.

Background And Objectives: To characterize the clinical and ellipsoid zone (EZ) integrity outcomes in surgical intervention for symptomatic vitreomacular traction (VMT), and to evaluate the utility of intraoperative optical coherence tomography (OCT) during VMT surgery.

Patients And Methods: This was a post-hoc analysis of eyes in the DISCOVER study undergoing pars plana vitrectomy (PPV) with intraoperative OCT for VMT-related macular disease. Data were collected prospectively on feasibility and utility of intraoperative OCT, with follow-up lasting 12 months.

Results: Forty-three eyes of 41 patients were included and mean visual acuity improved from 20/96 to 20/45 ( < .001). Intraoperative OCT provided information that impacted surgical decision-making in eight patients (18.6%). EZ integrity metrics significantly improved from baseline to 12 months and directly correlated with functional outcomes ( < .001).

Conclusions: Retinal function and morphology improved significantly following PPV for VMT. Intraoperative OCT provided surgeon-perceived valuable information in select cases. Further research is needed to determine whether this information impacts overall surgical outcomes. .
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http://dx.doi.org/10.3928/23258160-20210913-01DOI Listing
October 2021

Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial.

J Pers Med 2021 Sep 4;11(9). Epub 2021 Sep 4.

Retina Consultants of Texas, Retina Consultants of America, Houston, TX 77030, USA.

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% ( = 0.73) and 23.6% ( = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of (PRN) visits requiring IAI was significantly higher in year 2 versus 1 ( < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 ( < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.
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http://dx.doi.org/10.3390/jpm11090885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465170PMC
September 2021

Longitudinal Ellipsoid Zone and Outer Retinal Integrity Dynamics Following Epiretinal Membrane Surgery.

Retina 2021 Sep 17. Epub 2021 Sep 17.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland OH Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland OH.

Purpose: To quantify ellipsoid zone (EZ) changes in integrity following epiretinal membrane (ERM) surgery, correlate findings to visual acuity (VA), and determine predictors for prognosis.

Methods: A post-hoc analysis of eyes undergoing ERM surgery pooled from the prospective DISCOVER intraoperative optical coherence tomography (iOCT) study and eyes undergoing conventional ERM surgery without iOCT. Quantitative EZ features were extracted using a multi-layer machine learning enabled automated segmentation platform following image analyst review/correction for segmentation accuracy. VA and EZ integrity were quantitatively assessed and correlated before and after ERM surgery. Multiple linear regression was performed to assess pre-operative VA and EZ features as predictors for improvement in VA or EZ integrity.

Results: There were 177 eyes from 177 subjects that underwent ERM surgery from the DISCOVER and conventional arms. Improvement in VA and multiple EZ integrity features was noted after ERM surgery, including EZ partial attenuation and EZ-retinal pigment epithelium (RPE) volume (p<0.05). A reduction in EZ partial attenuation and increase in EZ-RPE central subfield thickness (EZ-RPE CST) was significantly correlated with improved VA after ERM surgery (p<0.05). More robust EZ-RPE CST at baseline predicted VA improvement after ERM peel in regression modeling (β=0.005, p<0.05).

Conclusions: Longitudinal assessment of EZ features demonstrate significant postoperative improvement in multiple EZ integrity metrics following ERM surgery. Improving EZ integrity was correlated to improving VA. EZ integrity and visual acuity were significant predictors in regression modeling and may have value in clinical prognostication.
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http://dx.doi.org/10.1097/IAE.0000000000003306DOI Listing
September 2021

Deep learning-enabled ultra-widefield retinal vessel segmentation with an automated quality-optimized angiographic phase selection tool.

Eye (Lond) 2021 Aug 9. Epub 2021 Aug 9.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.

Objectives: To demonstrate the feasibility of a deep learning-based vascular segmentation tool for UWFA and evaluate its ability to automatically identify quality-optimized phase-specific images.

Methods: Cumulative retinal vessel areas (RVA) were extracted from all available UWFA frames. Cubic splines were fitted for serial vascular assessment throughout the angiographic phases of eyes with diabetic retinopathy (DR), sickle cell retinopathy (SCR), or normal retinal vasculature. The image with maximum RVA was selected as the optimum early phase. A late phase frame was selected at a minimum of 4 min that most closely mirrored the RVA from the selected early image. Trained image analysts evaluated the selected pairs.

Results: A total of 13,980 UWFA sequences from 462 sessions were used to evaluate the performance and 1578 UWFA sequences from 66 sessions were used to create cubic splines. Maximum RVA was detected at a mean of 41 ± 15, 47 ± 27, 38 ± 8 s for DR, SCR, and normals respectively. In 85.2% of the sessions, appropriate images for both phases were successfully identified. The individual success rate was 90.7% for early and 94.6% for late frames.

Conclusions: Retinal vascular characteristics are highly phased and field-of-view sensitive. Vascular parameters extracted by deep learning algorithms can be used for quality assessment of angiographic images and quality optimized phase selection. Clinical applications of a deep learning-based vascular segmentation and phase selection system might significantly improve the speed, consistency, and objectivity of UWFA evaluation.
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http://dx.doi.org/10.1038/s41433-021-01661-4DOI Listing
August 2021

Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression.

Br J Ophthalmol 2021 Jun 7. Epub 2021 Jun 7.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, USA

Background: This study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME).

Methods: The IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response.

Results: Twenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (p<0.05). High baseline VEGF and IL-6 were associated with dramatic reduction in macular leakage (p<0.05).

Conclusions: Baseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761372PMC
June 2021

Longitudinal Higher-Order OCT Assessment of Quantitative Fluid Dynamics and the Total Retinal Fluid Index in Neovascular AMD.

Transl Vis Sci Technol 2021 03;10(3):29

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, OH, USA.

Purpose: The purpose of this study was to evaluate the feasibility of assessing quantitative longitudinal fluid dynamics and total retinal fluid indices (TRFIs) with higher-order optical coherence tomography (OCT) for neovascular age-related macular degeneration (nAMD).

Methods: A post hoc image analysis study was performed using the phase II OSPREY clinical trial comparing brolucizumab and aflibercept in nAMD. Higher-order OCT analysis using a machine learning-enabled fluid feature extraction platform was used to segment intraretinal fluid (IRF) and subretinal fluid (SRF) volumetric components. TRFI, the proportion of fluid volume against total retinal volume, was calculated. Longitudinal fluid metrics were evaluated for the following groups: all subjects (i.e. treatment agnostic), brolucizumab, and aflibercept.

Results: Mean IRF and SRF volumes were significantly reduced from baseline at each timepoint for all groups. Fluid feature extraction allowed high-resolution assessment of quantitative fluid burden. A greater proportion of brolucizumab participants achieved true zero and minimal fluid (total fluid volume between 0.0001 and 0.001mm3) versus aflibercept participants at week 40. True zero fluid during q12 brolucizumab dosing was achieved in 36.6% to 38.5%, similar to the 25.6% to 38.5% during the corresponding q8 aflibercept cycles. TRFI was significantly reduced from baseline in all groups.

Conclusions: Higher-order OCT analysis demonstrates the feasibility of fluid feature extraction and longitudinal volumetric fluid burden and TRFI characterization in nAMD, supporting a unique opportunity for fluid burden assessment and the impact on outcomes.

Translational Relevance: Detection and characterization of disease activity is vital for optimal treatment of nAMD. Longitudinal assessment of fluid dynamics and the TRFI provide important proof of concept for future automated tools in characterizing disease activity.
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http://dx.doi.org/10.1167/tvst.10.3.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995350PMC
March 2021

LONGITUDINAL ELLIPSOID ZONE DYNAMICS AFTER MACULAR HOLE REPAIR IN THE DISCOVER STUDY: Structure-Function Assessment.

Retina 2021 May;41(5):915-920

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.

Purpose: To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair.

Methods: This was a post-hoc analysis of eyes in the DISCOVER study undergoing vitrectomy repair for MH. Anatomical and functional data were collected through one year postoperatively. An automated retinal layer segmentation platform was used for the assessment of outer retinal metrics and volumetric reconstruction of MH. Association of longitudinal ellipsoid zone features and baseline MH height, width, and volume with VA outcomes were investigated.

Results: Eighty-four eyes with MH were included. The mean baseline VA was 20 of 114 and increased to 20 of 45 (P < 0.001) at postoperative Month 12 (N = 45). Successful MH closure was achieved in 98.8% of cases. Ellipsoid zone integrity metrics significantly improved from baseline (P = 0.002) and postoperative Month 1 (P < 0.001) to post-operative Month 12. Ellipsoid zone metrics independently correlated with VA at all follow-up visits (P < 0.05). Increased baseline MH width and volume negatively correlated with the VA at postoperative Month 12 (P < 0.001). Preoperative VA and EZ integrity on optical coherence tomography were predictors for postoperative VA.

Conclusion: Baseline MH volumetric parameters and EZ parameters were associated with VA outcomes after repair.
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http://dx.doi.org/10.1097/IAE.0000000000002983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074992PMC
May 2021

Epiretinal Membrane Surgery Using Intraoperative OCT-Guided Membrane Removal in the DISCOVER Study versus Conventional Membrane Removal.

Ophthalmol Retina 2021 Dec 27;5(12):1254-1262. Epub 2021 Feb 27.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: To provide a comparative assessment of clinical outcomes between patients undergoing intraoperative OCT (iOCT) and conventional surgery for pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peel.

Design: Case-control retrospective, comparative assessment.

Participants: Patients undergoing PPV with membrane peel for ERM with eyes pooled from the prospective Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery (DISCOVER) iOCT study and eyes undergoing conventional ERM surgery without iOCT.

Methods: Visual acuity and OCT assessment before ERM surgery and at 1-, 3-, 6-, and 12-month follow-up after standard small-gauge PPV with iOCT feedback (iOCT DISCOVER group) or PPV with compulsory internal limiting membrane (ILM) peeling (conventional group). Visual acuity, central subfield thickness (CST), reoperation rate, and ERM recurrence were determined by record review and post hoc assessment of clinical OCTs after ERM peel.

Main Outcome Measures: Visual acuity and ERM recurrence.

Results: A total of 262 eyes were included. Visual acuity (VA) improved 11.9 letters in the iOCT group (P < 0.0001) and 12.1 letters in the conventional group (P < 0.0001) at 12 months after ERM surgery. Visual acuity improvement did not differ between the iOCT and conventional groups at 1, 3, 6, or 12 months after surgery (P > 0.05 for each time point). Preoperative mean CST decreased in the iOCT group (P < 0.0001) and conventional group (P < 0.0001) with no difference between groups in CST reduction at 12 months (P = 0.36). No reoperations or visually significant recurrent ERMs occurred in either cohort.

Conclusions: Intraoperative OCT-guided ERM removal without mandated ILM peeling provided similar VA and anatomic results to conventional ILM peeling for ERM. Future randomized prospective studies are needed to assess fully the possible role of iOCT in ERM surgery and to evaluate the potential impact of nonfoveal ERM persistence or recurrence in comparison with conventional surgery.
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http://dx.doi.org/10.1016/j.oret.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390556PMC
December 2021

Longitudinal Assessment of Ellipsoid Zone Integrity, Subretinal Hyperreflective Material, and Subretinal Pigment Epithelium Disease in Neovascular Age-Related Macular Degeneration.

Ophthalmol Retina 2021 Dec 26;5(12):1204-1213. Epub 2021 Feb 26.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, Ohio; Center for Ocular Research and Evaluation, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: To assess longitudinally the effect of anti-vascular endothelial growth factor (VEGF) treatment on ellipsoid zone (EZ) integrity, subretinal hyperreflective material (SHRM), and the sub-retinal pigment epithelium (sub-RPE) compartment in eyes with neovascular age-related macular degeneration (nAMD).

Design: Post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase 2 study comparing brolucizumab 6 mg with aflibercept 2 mg over 56 weeks.

Participants: Participants with treatment-naïve nAMD at the initiation of the trial were included in the analysis.

Methods: Eyes were evaluated with spectral-domain OCT at 4-week intervals in the OSPREY trial (n = 81). Spectral-domain OCT scans collected from each visit were segmented automatically using a proprietary, machine learning-enabled higher-order feature-extraction platform for retinal layer, SHRM, and sub-RPE boundary lines, which were evaluated and corrected as needed by masked trained graders. The current analysis focused only on patients evaluated with the Cirrus (Zeiss) platform (n = 28).

Main Outcome Measures: Outcome measures included change from baseline in EZ-RPE (i.e., photoreceptor outer segment) volume, EZ-RPE central subfield thickness (CST), total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume. The correlation between each of these measures and best-corrected visual acuity (BCVA) at each visit was evaluated.

Results: EZ-RPE volume and EZ-RPE CST showed significant increases, and total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume showed significant decreases from baseline at each visit from weeks 4 through 56 (P < 0.05 at each visit). Ellipsoid zone integrity measures and SHRM volume correlated significantly with BCVA at most visits (P < 0.05). No significant correlation was found between total sub-RPE volume and BCVA.

Conclusions: EZ integrity, SHRM, and sub-RPE disease features in eyes with nAMD showed improvement as early as week 4 of anti-VEGF treatment. EZ integrity measures and SHRM volume were predictors of visual acuity over the first year of treatment.
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http://dx.doi.org/10.1016/j.oret.2021.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387490PMC
December 2021

Real-Time Photographic- and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy: Randomized PRIME Trial Outcomes.

Am J Ophthalmol 2021 06 30;226:126-136. Epub 2021 Jan 30.

Retina Consultants of Texas, Houston, Texas, USA; Blanton Eye Institute (CCW), Houston Methodist Hospital, Houston, Texas, USA. Electronic address:

Purpose: To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME).

Design: Prospective, randomized phase 2 trial (PRIME).

Methods: A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI.

Results: Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P = .49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence.

Conclusions: The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.
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http://dx.doi.org/10.1016/j.ajo.2021.01.024DOI Listing
June 2021

Longitudinal assessment of quantitative ultra-widefield ischaemic and vascular parameters in sickle cell retinopathy.

Br J Ophthalmol 2020 Oct 31. Epub 2020 Oct 31.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA

Purpose: To evaluate longitudinal quantitative ischaemic and vasculature parameters, including ischaemic index, vessel area, length and geodesic distance in sickle cell retinopathy (SCR) on ultra-widefield fluorescein angiography (UWFA).

Methods: Optimal UWFA images from two longitudinal timepoints of 74 eyes from 45 patients with SCR were aligned and a common region of interest was determined. A deep-learning augmented ischaemia and vascular segmentation platform was used for feature extraction. Geodesic distance maps demonstrating the shortest distance within the vascular masks from the centre of the optic disc were created. Ischaemic index, vessel area, vessel length and geodesic distance were measured. Paired t-test and linear mixed effect model analysis were performed.

Results: Overall, 25 (44 eyes) patients with HbSS, 14 (19 eyes) with HbSC, 6 (11 eyes) with HbSthal and other genotypes were included. Mean age was 40.1±11.0 years. Mean time interval between two UWFA studies was 23.0±15.1 months (range: 3-71.3). Mean panretinal ischaemic index increased from 10.0±7.2% to 10.9±7.3% (p<0.005). Mean rate of change in ischaemic index was 0.5±0.7% per year. Mean vessel area (p=0.020) and geodesic distance (p=0.048) decreased significantly. Multivariate analysis demonstrated baseline ischaemic index and Goldberg stage are correlated with progression.

Conclusion: Longitudinal ischaemic index and retinal vascular parameter measurements demonstrate statistically significant progression in SCR. The clinical significance of these relatively small magnitude changes remains unclear but may provide insights into the progression of retinal ischaemia in SCR.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317241DOI Listing
October 2020

Automated Quality Assessment and Image Selection of Ultra-Widefield Fluorescein Angiography Images through Deep Learning.

Transl Vis Sci Technol 2020 09 17;9(2):52. Epub 2020 Sep 17.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.

Purpose: Numerous angiographic images with high variability in quality are obtained during each ultra-widefield fluorescein angiography (UWFA) acquisition session. This study evaluated the feasibility of an automated system for image quality classification and selection using deep learning.

Methods: The training set was comprised of 3543 UWFA images. Ground-truth image quality was assessed by expert image review and classified into one of four categories (ungradable, poor, good, or best) based on contrast, field of view, media opacity, and obscuration from external features. Two test sets, including randomly selected 392 images separated from the training set and an independent balanced image set composed of 50 ungradable/poor and 50 good/best images, assessed the model performance and bias.

Results: In the randomly selected and balanced test sets, the automated quality assessment system showed overall accuracy of 89.0% and 94.0% for distinguishing between gradable and ungradable images, with sensitivity of 90.5% and 98.6% and specificity of 87.0% and 81.5%, respectively. The receiver operating characteristic curve measuring performance of two-class classification (ungradable and gradable) had an area under the curve of 0.920 in the randomly selected set and 0.980 in the balanced set.

Conclusions: A deep learning classification model demonstrates the feasibility of automatic classification of UWFA image quality. Clinical application of this system might greatly reduce manual image grading workload, allow quality-based image presentation to clinicians, and provide near-instantaneous feedback on image quality during image acquisition for photographers.

Translational Relevance: The UWFA image quality classification tool may significantly reduce manual grading for clinical- and research-related work, providing instantaneous and reliable feedback on image quality.
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http://dx.doi.org/10.1167/tvst.9.2.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500112PMC
September 2020

Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.

Am J Ophthalmol 2021 02 5;222:328-339. Epub 2020 Sep 5.

Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Purpose: To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype.

Design: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial.

Methods: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers.

Results: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01).

Conclusions: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.
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http://dx.doi.org/10.1016/j.ajo.2020.08.047DOI Listing
February 2021

Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study.

Br J Ophthalmol 2021 08 22;105(8):1111-1115. Epub 2020 Aug 22.

The Tony and Leona Campane Center for Excellence in Image-guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, Ohio, USA

Background/aims: Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravital Afliberept for Retinal Nn-Perfusion in Proliferatie Diabtic etinopath(RECOVERY) study using an automated MA detection platform.

Methods: RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively.

Results: The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (-20.0% to -61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: -34.2%; p<0.001) and in zone 3 (mean -44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: -47.7%; p<0.001) and in zone 3 (mean: -59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group.

Conclusion: Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact.

Trial Registration Number: NCT02863354.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316952DOI Listing
August 2021

Implementation of the Addendum Guidelines for Peanut Allergy Prevention by US allergists, a survey conducted by the NIAID, in collaboration with the AAAAI.

J Allergy Clin Immunol 2020 10 1;146(4):875-883. Epub 2020 Aug 1.

Rho, Inc, Durham, NC.

Background: In 2017, the Addendum Guidelines for the Prevention of Peanut Allergy were published with recommendations on early introduction of peanut-containing foods based on infants' clinical history.

Objective: We sought to conduct a nationwide US survey to assess Guidelines implementation among allergists and immunologists who manage infants for food allergy.

Methods: Survey invitations were delivered to 3281 nonretired, US members of the American Academy of Asthma, Allergy & Immunology, board certified in allergy and immunology. The survey assessed awareness and implementation of the Guidelines and barriers to implementation. Descriptive statistics were generated.

Results: Twenty-nine percent (946 of 3281) of surveyed allergists/immunologists responded, and 87.1% (825 of 946) of responders met eligibility criteria. Among eligible responders, 97.1% were aware of the Guidelines. Of these, 64.5% reported full implementation of the Guidelines as published, 34.4% reported partial implementation, and 1.1% reported using none of the Guidelines. Barriers to Guidelines use included parental (47.6%) and self (21.8%) concerns about allergic reactions, lack of referrals (33.6%), parents uninterested in early feeding (28.2%), and lack of clinic time (20.9%). The 2 most common deviations from the Guidelines were considering additional factors not specified in the Guidelines such as family history (50.2%) and conducting skin prick testing in non-high-risk children (43.9%). Of respondents using the Guidelines, 45.7% indicated they needed more education or training.

Conclusions: Essentially all allergists/immunologists who responded to the survey reported full or partial Guidelines implementation. Parental concerns and lack of referrals are major identifiable barriers. Improved Guidelines messaging to parents and referring physicians is warranted.
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http://dx.doi.org/10.1016/j.jaci.2020.07.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590504PMC
October 2020

Assessment of Pediatrician Awareness and Implementation of the Addendum Guidelines for the Prevention of Peanut Allergy in the United States.

JAMA Netw Open 2020 07 1;3(7):e2010511. Epub 2020 Jul 1.

Rho Federal Systems Division Inc, Durham, North Carolina.

Importance: The 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States recommend that pediatricians assess infant peanut allergy risk and introduce peanut in the diet at age 4 to 6 months. Early introduction has the potential to prevent peanut allergy development.

Objectives: To measure the rates of guideline awareness and implementation and to identify barriers to and factors associated with implementation among US pediatricians.

Design, Setting, And Participants: This population-based study survey used a 29-item electronic survey instrument that was administered to pediatricians practicing across the United States from June 1, 2018, to December 1, 2018. Invitations to complete a survey were emailed to all pediatricians in the American Academy of Pediatrics vendor database. Eligible participants were nonretired US-based pediatricians providing general care to infants aged 12 months or younger.

Main Outcomes And Measures: The primary outcome was the prevalence of guideline implementation, which was measured by 1 survey item about awareness followed by a second item about implementation. Secondary outcomes included identification of guidelines-focused services provided by pediatricians, knowledge of the guidelines (measured with 3 clinical scenarios), barriers to guideline implementation, need for training, and facilitators of guideline implementation.

Results: A total of 1781 pediatricians were eligible to participate and completed the entire survey. Most respondents self-identified as white (1287 [72.5%]) and female (1210 [67.4%]) individuals. Overall, 1725 (93.4%; 95% CI, 92.2%-94.5%) pediatricians reported being aware of the guidelines. Of those pediatricians who had knowledge of the guidelines, 497 (28.9%; 95% CI, 26.8%-31.1%) reported full implementation and 1105 (64.3%; 95% CI, 62.0%-66.6%) reported partial implementation. Common barriers to implementation included parental concerns about allergic reactions (reported by 575 respondents [36.6%; 95% CI, 34.3%-39.1%]), uncertainty in understanding and correctly applying the guidelines (reported by 521 respondents [33.2%; 95% CI, 30.9%-35.6%]), and conducting in-office supervised feedings (reported by 509 respondents [32.4%; 95% CI, 30.1%-34.8%]). Many pediatricians (1175 [68.4%; 95% CI, 66.1%-70.5%]) reported a need for further training on the guidelines.

Conclusions And Relevance: This survey found that most pediatrician respondents appeared to know of the 2017 guidelines, but less than one-third of respondents reported full implementation. Results of this study may inform future efforts to eliminate barriers to guideline implementation and adherence, thereby reducing the incidence of peanut allergy in infants.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.10511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364336PMC
July 2020

iOCT-assisted macular hole surgery: outcomes and utility from the DISCOVER study.

Br J Ophthalmol 2021 03 6;105(3):403-409. Epub 2020 May 6.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland, Ohio, USA

Background/aims: This study aimed to characterise the clinical outcomes and utility of intraoperative optical coherence tomography (iOCT)-assisted macular hole (MH) repair.

Methods: This was a post hoc analysis of eyes in the etermination of feasibility of ntraoperative pectral domain microscope ombined/integrated CT isualization during n face etinal and ophthalmic surgery (DISCOVER) study undergoing surgical MH repair with use of iOCT. Functional and surgical outcome data were collected through 12 months postoperatively. MH closure rate, postoperative visual acuity (VA), percentage of cases in which iOCT provided valuable feedback and altered surgical decision making were measured.

Results: Eighty-four eyes were included in this study. The mean preoperative VA measured 20/114. The mean postoperative VA improved to 20/68 (p<0.001) at month 1, 20/48 (p<0.001) at month 3 and 20/45 (p<0.001) at month 12 or later. In 43 cases (51%), surgeons reported that iOCT provided valuable information (eg, confirming release of vitreomacular traction and identification of occult residual membranes). In 10 cases (12%), iOCT data specifically altered surgical decision making. Postoperative day 1 transtamponade OCT confirmed tissue apposition and apparent hole closure in 74% of eyes (21/26). All five open holes on postoperative day 1 closed following positioning. Single-surgery MH closure was achieved in 97.6% of cases. One persistent MH was successfully closed with a subsequent surgical repair for a final overall closure rate of 98.8%. Due to chronicity and MH size, additional repair was not recommended for the single remaining persistent MH.

Conclusion: This study suggests that iOCT may have important utility in MH surgery, including impacting surgical decision making. iOCT-assisted MH surgery resulted in significant improvement in VA and high single-surgery success rate.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316045DOI Listing
March 2021

Conventional Microscope-Integrated Intraoperative OCT Versus Digitally Enabled Intraoperative OCT in Vitreoretinal Surgery in the DISCOVER Study.

Ophthalmic Surg Lasers Imaging Retina 2020 04;51(4):S37-S43

Background And Objective: To compare conventional microscope-integrated intraoperative optical coherence tomography (iOCT) and digitally enabled microscope-integrated iOCT in vitreoretinal surgery.

Patients And Methods: In this post-hoc analysis of the DISCOVER prospective iOCT study, two surgical groups were compared: (1) conventional iOCT and (2) digitally enabled iOCT. Surgeon questionnaires were collected immediately following surgery.

Results: A total of 187 subjects were included in the study: 91 in the conventional iOCT group and 96 in the digitally enabled iOCT group. There were no differences in surgeon-perceived iOCT utility between the two groups. There was significantly higher surgical field-based visualization of the iOCT datastream in the digitally enabled iOCT group (67.7% vs. 3.3%; P < .0001). Reported significant back discomfort (1.0% vs. 18.7%; P < .0001) and headaches (5.2% vs. 20.9%; P < .002) were lower in the digitally enabled iOCT group.

Conclusions: Feasibility and utility of iOCT were similar in both groups. Digitally enabled iOCT datastream enabled increased attention on the surgical field during OCT review. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S37-S43.].
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http://dx.doi.org/10.3928/23258160-20200401-05DOI Listing
April 2020

Use of OCTA Capillary Perfusion Density Measurements to Detect and Grade Macular Ischemia.

Ophthalmic Surg Lasers Imaging Retina 2020 04;51(4):S30-S36

Background And Objective: To compare optical coherence tomography angiography (OCTA) capillary perfusion density (CPD) measurements of normal eyes and eyes with macular ischemia (MI).

Patients And Methods: AVATAR is an institutional review board-approved, prospective, observational imaging study using the Avanti RTVue XR HD. OCTA reports were reviewed for the presence of MI. Qualitative MI grading was performed, and CPD metrics in the superficial and deep fovea and parafovea were analyzed. A normal eye cohort was identified for comparative assessment.

Results: The MI and normal cohorts included 55 and 58 eyes, respectively. Compared to normal eyes, eyes with MI had significantly lower CPD values in all regions. There was a statistically significant correlation between qualitative MI grade and VA in the superficial (P = .003) and deep plexuses (P = .029). Only deep parafoveal CPD values demonstrated correlation with VA (P = .043).

Conclusions: Eyes with MI determined by masked qualitative OCTA grading demonstrated significantly reduced CPD values compared to normal eyes. Categorical assessment of MI severity correlated with VA. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S30-S36.].
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http://dx.doi.org/10.3928/23258160-20200401-04DOI Listing
April 2020

Intraoperative OCT-Assisted Retinal Detachment Repair in the DISCOVER Study: Impact and Outcomes.

Ophthalmol Retina 2020 04 9;4(4):378-383. Epub 2019 Nov 9.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: The purpose of this study is to evaluate intraoperative OCT (iOCT) utility and outcomes during retinal detachment (RD) repair.

Design: The Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) intraoperative OCT study is a prospective Institutional Review Board-approved study.

Participants: Participants in the DISCOVER study undergoing surgical repair for RD.

Methods: This was a post hoc analysis of eyes in the DISCOVER study undergoing surgical repair for RDs. Inclusion criteria included iOCT after perfluorocarbon liquid placement and at least 6 months follow-up. Exclusion criteria included severe retinal pathology unrelated to RD. Surgeons completed standardized questionnaires after each case evaluating the iOCT instrument's utility. Functional and surgical outcome data were collected at the latest available time point between 6 and 12 months. Outcomes were evaluated in 2 groups: uncomplicated primary and complex cases.

Main Outcome Measures: Intraoperative OCT utility, single-surgery success, and visual acuity outcomes.

Results: A total of 103 eyes were included in this study: 51 uncomplicated primary and 52 complex cases. Intraoperative OCT provided valuable information in 36% of cases. In 12% of cases, iOCT data directly altered surgical decision making. There was a significantly higher rate of valuable iOCT feedback in complex cases compared with primary cases (50% vs. 22%, P < 0.01). Among primary cases, 48 (94%) had successful single surgery repair with a mean postoperative visual acuity of 20/47 compared with the complex group's 75% single surgery success (n=39) and mean postoperative visual acuity of 20/92.

Conclusions: This study affirms the potential impact of iOCT in assisting select cases of RD repair, particularly with complex pathology. The single surgery success rate was good with more than 80% of cases successfully repaired with 1 surgery.
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http://dx.doi.org/10.1016/j.oret.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150644PMC
April 2020

Impact of Drusen Burden on Incidence of Subclinical CNV With OCTA.

Ophthalmic Surg Lasers Imaging Retina 2019 12;51(1):22-30

Background And Objective: To evaluate the impact of drusen burden on the detection of subclinical choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) in nonexudative age-related macular degeneration (AMD).

Patients And Methods: A subanalysis of the AVATAR study, subjects diagnosed with nonexudative AMD without subfoveal atrophy were included. Subclinical CNV was assessed using OCTA software, and drusen burden was graded utilizing the advanced retinal pigment epithelium (RPE) analysis.

Results: Among eligible 58 eyes, 26 eyes (45%) had high drusen burden. Of the three eyes (5%) that demonstrated subclinical CNV, only one eye had high drusen burden, and all three eyes had neovascular AMD in the fellow eye. Extrafoveal RPE atrophy (odds ratio [OR] = 20.0; 95% confidence interval [CI], 1.53-261) and older age (OR = 1.27; 95% CI, 1.01-1.59) were predictive factors for subclinical CNV.

Conclusion: Extrafoveal RPE atrophy, older age, and fellow-eye CNV were significant risk factors for underlying subclinical CNV in nonexudative AMD. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:22-30.].
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http://dx.doi.org/10.3928/23258160-20191211-03DOI Listing
December 2019

RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY.

Retina 2020 Nov;40(11):2175-2183

Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Purpose: Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept.

Methods: Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated.

Results: Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34).

Conclusion: Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing.

Trial Registration: RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.
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http://dx.doi.org/10.1097/IAE.0000000000002727DOI Listing
November 2020

Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease after Aflibercept Therapy: The PERMEATE Study.

Ophthalmol Retina 2020 02 10;4(2):154-163. Epub 2019 Sep 10.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address:

Purpose: To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAIs).

Design: Prospective open-label study (clinicaltrials.gov identifier, NCT02503540).

Participants: Thirty-one treatment-naive eyes with foveal-involving retinal edema secondary to DME and RVO.

Methods: Participants received 2 mg IAI every 4 weeks for the first 6 months, followed by 2 mg every 8 weeks. Ultra-widefield fluorescein angiography (UWFA; California Optos [Optos, Dunfermline, United Kingdom]) and spectral-domain OCT (Cirrus; Zeiss, Oberkochen, Germany) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events also were collected.

Main Outcome Measures: The primary end point was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA.

Results: Mean age was 67.1 years. At month 12, visual acuity significantly improved by a mean of 18.4±21.4 letters (P < 0.0001), and central subfield thickness also improved significantly, with a mean reduction of 301.3±250.3 μm (P < 0.0001). Mean panretinal leakage index improved significantly, decreasing from 3.4% at baseline to 0.5% at month 6 (P <0.0001) and 0.4% at month 12 (P < 0.0001). Panretinal ischemic index did not demonstrate any significant change but showed a nonsignificant increase from 5.5% at baseline to 6.1% at month 6 (P = 0.315) and 8.7% at month 12 (P = 0.193). Eyes with DME showed a decrease in leakage index from 3.5±2.7% at baseline to 1.6±0.8% at month 12 (P = 0.018) and overall stability in ischemic index from 5.0±4.1% at baseline to 4.7±3.5% at month 12 (P = 0.689). Participants with RVO showed a decrease in leakage index from 3.3±1.1% at baseline to 0.02±0.03% at 12 months (P < 0.0001) and a nonsignificant increase in ischemic index from 5.9±4.5% at baseline to 12.6±9.8% at month 12 (P = 0.172).

Conclusions: Intravitreal aflibercept injections resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended toward worsening.
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http://dx.doi.org/10.1016/j.oret.2019.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024601PMC
February 2020

Quantitative Ultra-Widefield Angiographic Features and Associations with Diabetic Macular Edema.

Ophthalmol Retina 2020 01 28;4(1):49-56. Epub 2019 Aug 28.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms.

Design: Retrospective image analysis study.

Participants: Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography.

Methods: OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated.

Main Outcome Measures: Factors associated with the presence and severity of DME.

Results: A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P = 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P = 0.0002 and P = 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P = 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01).

Conclusions: Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.
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http://dx.doi.org/10.1016/j.oret.2019.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944750PMC
January 2020

Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count.

Ophthalmology 2019 11 8;126(11):1527-1532. Epub 2019 Jun 8.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count.

Design: Retrospective image analysis study.

Methods: Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history.

Main Outcome Measures: Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count.

Results: Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity.

Conclusions: Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.
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http://dx.doi.org/10.1016/j.ophtha.2019.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810836PMC
November 2019

Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography.

Br J Ophthalmol 2020 04 18;104(4):500-503. Epub 2019 Jul 18.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Instute, Cleveland, Ohio, USA

Background/aimsUltra-widefield fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The present study assesses the consistency/repeatability of an automated assessment platform for the characterisation of retinal vascular features, quantification of microaneurysms (MA) and leakage foci in UWFA images.

Methods: An Institutional Review Board-approved retrospective image analysis study was performed on UWFA images. For each eye, two arteriovenous-phase images and two late-phase images were selected. Automated assessment was performed for retinal vascular features, MA identification and leakage segmentation. Panretinal and zonal assessment of metrics was performed.

Results: There was a significant correlation between paired time points for retinal vessel area and vessel length on early images (Pearson r=0.92, p<0.0001; Pearson r=0.94, p<0.0001) and late images (Pearson r=0.92, p<0.0001; Pearson r=0.92, p<0.0001, respectively). Panretinal and zonal MA counts demonstrated high repeatability between images (all p<0.0001). Similarly, panretinal leakage area and zonal leakage areas were highly correlated (all p<0.001).

Conclusion: This automated algorithm demonstrated very strong intrastudy correlation between paired time points in the same phases of the angiogram for quantifying retinal vascular characteristics, MA count and leakage parameters in UWFA images. These findings suggest significant flexibility in the platform for consistency in evaluating metrics over time and is encouraging for longitudinal assessment opportunities.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314416DOI Listing
April 2020

Longitudinal ellipsoid zone and subretinal fluid mapping following ocriplasmin injection in the prospective observational ORBIT trial.

Br J Ophthalmol 2020 03 27;104(3):410-415. Epub 2019 Jun 27.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States

Background: Ocriplasmin is approved for the treatment of symptomatic vitreomacular traction (VMT). However, several retrospective reports have identified ellipsoid zone (EZ) alterations on spectral domain optical coherence tomography (SDOCT) after ocriplasmin injection. This report quantitatively analysed outer retinal changes after intravitreal ocriplasmin.

Methods: Ocriplasmin Research to Better Inform Treatment is a prospective, observational phase IV clinical study where subjects received a single intravitreal injection of ocriplasmin for symptomatic VMT. Macular cube scans were imported into a semiautomated EZ mapping and fluid feature extraction software for SDOCT analysis. Change in visual acuity, VMT release, macular hole (MH) closure, EZ integrity/volume and subretinal fluid (SRF) volume on SDOCT macular cube scans were recorded and analysed.

Results: This analysis included 55 participants with 6 months of follow-up. Intravitreal ocriplasmin injection caused VMT release in 67% and MH closure in 82% of participants. Visual acuity improved by 4.5 letters (p<0.05) in the whole cohort and by 6.0 letters (p<0.05) in participants with VMT release. EZ volume was reduced by 23.4% at week 1 (p<0.001) and recovered to baseline by between months 3 and 6. EZ volume loss at week 1 did not correlate with ETDRS acuity at final visit.

Conclusion: Ocriplasmin treatment resulted in VMT release, MH closure and visual acuity gains in a significant portion of eyes. EZ volume was significantly reduced at week 1, but recovered to baseline levels by final follow-up and was not associated with final visual acuity.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314142DOI Listing
March 2020

Intraoperative OCT Features and Postoperative Ellipsoid Mapping in Primary Macula-Involving Retinal Detachments from the PIONEER Study.

Ophthalmol Retina 2019 03 18;3(3):252-257. Epub 2018 Oct 18.

The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: Intraoperative OCT (iOCT) has enabled visualization of subtle structural details during surgical interventions, including retinal detachment repair. The purpose of this study was to evaluate iOCT findings during retinal detachment repair and to assess their impact on anatomic and functional outcomes, including outer retinal integrity.

Design: The PIONEER Intraoperative and Perioperative OCT Study is a prospective cohort, institutional review board-approved study.

Participants: Participants in the PIONEER undergoing surgical repair for primary macula-involving retinal detachment.

Methods: This was a post hoc analysis of all eyes in the PIONEER undergoing surgical repair with primary macula-involving retinal detachments. Inclusion criteria included iOCT after perfluorocarbon liquid (PFO) placement, visualization of the foveal center on iOCT, and images of sufficient quality for quantitative assessment of submacular fluid volume. Exclusion criteria included recurrent retinal detachment, proliferative vitreoretinopathy, and a lack of postoperative OCT data after gas bubble resolution. Subretinal fluid volume on iOCT imaging was quantified. Qualitative review of iOCT images was performed for visualization of outer retinal bands, fluid, and retinal corrugations. Postoperative OCT images were analyzed using an ellipsoid zone (EZ) mapping platform to evaluate and quantify outer retinal metrics. Postoperative OCT images also were reviewed qualitatively for persistent subretinal fluid. Associations between various anatomic and functional outcomes were assessed.

Main Outcome Measures: Presence of intraoperative subretinal fluid under PFO tamponade, postoperative persistent subretinal fluid, postoperative visual acuity at 1 year, and EZ integrity at 1 year.

Results: Fifteen eyes of 15 patients were analyzed. All 15 eyes (100%) showed subretinal fluid on iOCT. All eyes demonstrated spontaneous fluid resolution on follow-up OCT imaging. Increased intraoperative subretinal fluid volume under PFO tamponade trended toward significantly worse visual acuity outcome (P = 0.07). Postoperative quantitative EZ integrity at 12 months directly correlated with visual outcome (P = 0.01).

Conclusions: Intraoperative subretinal fluid persists under PFO tamponade with high frequency in eyes undergoing retinal detachment repair, but this fluid does not seem to be associated with persistent postoperative subretinal fluid. Postoperative EZ integrity is associated with visual acuity outcome, and intraoperative subretinal fluid volume under PFO tamponade also may be linked to visual outcomes.
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http://dx.doi.org/10.1016/j.oret.2018.10.006DOI Listing
March 2019
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