Publications by authors named "Peter K Kaiser"

205 Publications

Efficacy and Safety of Biosimilar FYB201 Compared With Ranibizumab in Neovascular Age-Related Macular Degeneration.

Ophthalmology 2021 May 3. Epub 2021 May 3.

Department of Ophthalmology, University of Bonn, Bonn, Germany;; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.

Purpose: This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD).

Design: This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study.

Participants: A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239).

Methods: Patients received FYB201 or ranibizumab 0.5 mg by intravitreal injection in the study eye every four weeks.

Main Outcome Measures: The primary end point was change from baseline in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks prior to the third monthly intravitreal injection. Biosimilarity of FYB201 to its originator was assessed via a two-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters.

Results: BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups.

Conclusions: FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.031DOI Listing
May 2021

Retinal Fluid and Thickness as Measures of Disease Activity in Neovascular Age-Related Macular Degeneration.

Retina 2021 May 3. Epub 2021 May 3.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA Retina Consultants of Houston; Retina Consultants of America; Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA Sierra Eye Associates, Reno, NV, USA; University of Nevada, Reno School of Medicine, Reno, NV, USA Byers Eye Institute, Stanford University, Palo Alto, CA, USA Novartis Pharmaceuticals, East Hanover, NJ, USA.

Purpose: Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration (nAMD), as evidenced by clinical trials that have used these features for inclusion criteria, re-treatment criteria, and outcome measures of the efficacy of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: A literature review of anatomical measures of disease activity was conducted.

Results: Treatment goals for nAMD include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. Change in retinal thickness has been found to correlate with change in visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity while the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice.

Conclusions: Retinal thickness and retinal fluid are common anatomical measures of disease activity in nAMD. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in nAMD.
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http://dx.doi.org/10.1097/IAE.0000000000003194DOI Listing
May 2021

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

Ophthalmol Retina 2021 Feb 27. 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
February 2021

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

Ophthalmol Retina 2021 Feb 26. 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
February 2021

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.

Ophthalmology 2020 Nov 15. Epub 2020 Nov 15.

Ophthalmic Consultants of Boston, Boston, Massachusetts. Electronic address:

Purpose: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).

Design: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).

Participants: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).

Methods: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.

Main Outcome Measures: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.

Results: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.

Conclusions: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.
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http://dx.doi.org/10.1016/j.ophtha.2020.11.011DOI Listing
November 2020

Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors.

Ophthalmol Retina 2020 Oct 12. Epub 2020 Oct 12.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Purpose: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center.

Design: Retrospective, institutional review board-approved study.

Participants: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016.

Methods: Intravitreal injection.

Main Outcome Measures: Complication occurrence within 15 days of injection.

Results: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications.

Conclusions: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.
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http://dx.doi.org/10.1016/j.oret.2020.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548755PMC
October 2020

The Efficacy of Conbercept in Polypoidal Choroidal Vasculopathy: A Systematic Review.

J Ophthalmol 2020 13;2020:4924053. Epub 2020 Aug 13.

Cole Eye Institute, Cleveland, OH, USA.

Methods: Thirty studies with 1308 eyes were identified and included in this study. The primary outcome measures were best-corrected visual acuity (BCVA), and secondary outcomes were optical coherence tomography characteristics and polyp regression rates. The pooled results were calculated by the random-effect or fixed-effect model according to the heterogeneity of the data.

Results: Despite a large standard deviation in means (SMD) improvement for BCVA and central retinal thickness (CRT) in the conbercept group, there was no statistically significant difference in the other outcomes compared to ranibizumab and aflibercept. However, there was a greater polyp regression rate in the conbercept group at 12 months.

Conclusions: This systematic review indicates that conbercept may achieve similar BCVA and CRT improvements as ranibizumab and aflibercept, with a superior rate of polyp regression at 12 months.
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http://dx.doi.org/10.1155/2020/4924053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442996PMC
August 2020

Twenty-Four-Month OCTA Assessment in Diabetic Patients Undergoing Fixed-Interval Intravitreal Aflibercept Therapy.

Ophthalmic Surg Lasers Imaging Retina 2020 08;51(8):448-455

Background And Objective: Evaluate capillary perfusion density (CPD) in patients with diabetic macular edema (DME) undergoing fixed intravit-real aflibercept injections (IAI) through 24 months.

Patients And Methods: Prospective, interventional, single-arm study enrolling 20 patients with persistent DME. Patients received IAI every 4 weeks until DME resolution followed by extension to every 8 weeks. Optical coherence tomography angiography was obtained at baseline, 6, 12, and 24 months.

Results: Sixteen of 20 eyes completed the study. Baseline mean central subfield thickness was 420 µm, which improved to 251 µm (P < .001). The mean best-corrected visual acuity (BCVA) improved by 5.5 letters (P = .042). The whole superficial CPD decreased by 5.3% (P = .001) and the deep CPD decreased by 4.4% (P = .009). Better BCVA correlated with less CPD loss within the superficial parafovea (r = +0.66 [0.23, 0.88]; P = .006) and whole (r = +0.60 [0.12, 0.85]; P = .017) areas.

Conclusion: Superficial and deep CPD decreased despite fixed IAI through 24 months. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:448-455.].
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http://dx.doi.org/10.3928/23258160-20200804-05DOI Listing
August 2020

Visual Acuity Variability: Comparing Discrepancies between Snellen and ETDRS Measurements among Subjects Entering Prospective Trials.

Ophthalmol Retina 2021 03 23;5(3):224-233. Epub 2020 Apr 23.

Retina Consultants of Houston, Retina Consultants of America, Houston, Texas; Blanton Eye Institute, Houston Methodist Hospital & Weill Cornell Medical College, Houston, Texas. Electronic address:

Purpose: To compare the variability between Snellen visual acuity (VA) and Early Treatment Diabetic Retinopathy (ETDRS) best-corrected VA (BCVA) measurements.

Design: Retrospective chart review.

Participants: Eyes from subjects entering 12 prospective retinal trials in a large, urban retina practice.

Methods: Eyes were included if a Snellen VA measurement was performed at the visit preceding trial screening and VA was better than counting fingers. Snellen VA and ETDRS BCVA were then converted to logarithm of the minimum angle of resolution (logMAR) units, and the variability between measurements was calculated.

Main Outcome Measures: Outcome measures include VA variability among disease states, absolute VA, and central subfield thickness (CST).

Results: A total of 773 eyes of 413 subjects were identified with a mean of 27.2 days (median, 19; 95% confidence interval [CI], 25.1-29.3) between measurements. Mean Snellen and ETDRS measurements were 0.40 (20/50) and 0.27 logMAR (20/40), respectively. Overall, mean ETDRS BCVA was 6.1 letters better than Snellen VA (median, 5.8; 95% CI, 5.3-7.0; P < 0.05); 76.6% of eyes had improved ETDRS. Restricting the number of days between measurements did not result in any meaningful differences from this directionality. Among eyes with worse VA, variation was more pronounced than among eyes with better VA; eyes 20/25 or better were a mean +1.9 letters better on ETDRS testing (P < 0.05) and eyes 20/160 or worse were a mean +12.6 letters better on ETDRS testing (P < 0.05). Subgroup analyses by disease state found statistically significantly better vision measurements with the ETDRS protocol compared with Snellen in 4 of the 5 disease states studied. Although lens status did not affect the extent of discrepancy between ETDRS and Snellen measurements, amount of retinal edema (CST) did: increased CST correlated with increased variability.

Conclusions: The ETDRS protocol BCVA measurement resulted in significantly better scores when compared with Snellen VA measurements. This difference was more pronounced among eyes with worse VA. Additionally, specific retinal disease states and anatomic variables such as extent of retinal edema (CST) may have a meaningful impact on the anticipated variability between ETDRS and Snellen VA measurement.
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http://dx.doi.org/10.1016/j.oret.2020.04.011DOI Listing
March 2021

Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date.

Clin Ophthalmol 2020 19;14:1349-1355. Epub 2020 May 19.

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

Age-related macular degeneration (AMD) is one of the leading causes of blindness in older adults worldwide. The advent of intravitreal neutralization of vascular endothelial growth factor (VEGF) has revolutionized the management of patients with neovascular AMD, but current anti-VEGF therapies carry a high threshold of patient burden. The ranibizumab port delivery system (PDS) is an implanted, refillable reservoir that continuously supplies the anti-VEGF medication ranibizumab directly into the vitreous, eliminating the need for frequent intravitreal injections. It has most recently been evaluated in the Phase II LADDER trial demonstrating the efficacy and safety of the PDS, with Phase III trials currently underway. This review presents both the promise and drawbacks of the PDS in the treatment of AMD from the current literature.
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http://dx.doi.org/10.2147/OPTH.S194234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245454PMC
May 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

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

Detection of Choroidal Neovascular Membrane Beneath Pigment Epithelial Detachment Using SD-OCTA.

Ophthalmic Surg Lasers Imaging Retina 2019 10;50(10):620-626

Background And Objective: To identify choroidal neovascular membrane (CNVM) associated with spectral-domain optical coherence tomography (SD-OCT)-defined pigment epithelial detachment (PED) using SD-OCT angiography (SD-OCTA).

Patients And Methods: Sixty-nine patients with same-day OCT and OCTA imaging were reviewed, and 41 eyes of 29 patients with PEDs were included. OCTs were analyzed for PED type, fluid, and subretinal hyperreflective material (SHRM).

Results: Twenty-seven eyes (66%) demonstrated CNVM on OCTA beneath all subtypes of PED. Twenty-two eyes (75.9%) with fluid or SHRM demonstrated CNVM on OCTA (P = .036). Fluid corresponded in a statistically significant manner with treatment (P = .0032), whereas SHRM did not (P = .613). OCTA-defined CNVM showed borderline statistically significant correlation to treatment (P = .05). Increased choroidal flow signal seen in 50% of eyes did not demonstrate statistically significant correlation to the presence of fluid on SD-OCT (P = .2798) or treatment decision (P = .678). A subset of 14 untreated eyes with CNVM was analyzed, 21% of which required treatment at subsequent visits.

Conclusions: OCTA-defined CNVM was seen in all subtypes of PED in clinically active and inactive disease. The role of OCTA in predicting need for treatment remains to be established. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:620-626.].
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http://dx.doi.org/10.3928/23258160-20191009-04DOI Listing
October 2019

Higher-Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index.

Ophthalmol Retina 2019 12 6;3(12):1056-1066. Epub 2019 Jul 6.

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

Purpose: To investigate retinal fluid features and ellipsoid zone (EZ) integrity dynamics on spectral-domain OCT (SD-OCT) in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept injection (IAI) in the VISTA-DME study.

Design: A post hoc subanalysis of a phase III, prospective clinical trial.

Participants: Eyes received either IAI 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly doses (2q8).

Methods: All eyes from the VISTA Phase III study in the IAI groups imaged with the Cirrus HD-OCT system (Zeiss, Oberkochen, Germany) were included. The OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines that were manually corrected for assessment of change in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point.

Main Outcome Measures: The feasibility of volumetric assessment of higher-order OCT-based retinal parameters and its correlation with best-corrected visual acuity (BCVA).

Results: Overall, 106 eyes of 106 patients were included. Specifically, 52 eyes of 52 patients were included in the IAI 2q4 arm, and 54 eyes of 54 patients were included in the IAI 2q8 arm. Ellipsoid zone integrity metrics significantly improved from baseline to week 100, including central macular mean EZ to retinal pigment epithelium (RPE) thickness (2q4: 26.6 μm to 31.6 μm, P < 0.001; 2q8: 25.2 μm to 31.4 μm, P < 0.001). At week 100, central macular intraretinal fluid volume was reduced by >65% (P < 0.001) and central macular subretinal fluid volume was reduced by >99% in both arms (P < 0.001). Central macular retinal fluid index (RFI) significantly improved in both arms (2q4: 17.9% to 7.2%, P < 0.001; 2q8: 19.8% to 4.2%, P < 0.001). Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits.

Conclusions: Intravitreal aflibercept injection resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms and correlated with visual function.
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http://dx.doi.org/10.1016/j.oret.2019.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899163PMC
December 2019

Optical coherence tomography angiography characteristics of choroidal neovascularization requiring varied dosing frequencies in treat-and-extend management: An analysis of the AVATAR study.

PLoS One 2019 25;14(6):e0218889. Epub 2019 Jun 25.

The Tony and Leona Campane Center for Excellence in Image-guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.

Purpose: To evaluate optical coherence tomography angiography (OCTA) characteristics of choroidal neovascularization (CNV) in eyes requiring different treatment frequency of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (NVAMD).

Design: Prospective observational case series.

Methods: Subjects who had undergone anti-VEGF treatment for NVAMD in the AVATAR study were subdivided into 3 groups depending on required anti-VEGF dosing: (i) treat-and-extend requiring every 4-6 weeks dosing (TEq4-6w), (ii) treat-and-extend requiring every 7-12 weeks dosing (TEq7-12w), (iii) eyes not requiring injection within last 12 months (PRN >12mo). OCTA images were evaluated for the morphological characteristics of CNV and the choriocapillaris flow void.

Results: Study consisted 40 eyes of 31 patients with a mean age of 79.9 ± 6.2 years. CNV morphology analysis on OCTA was feasible in 29 (73%) eyes. Ninety percent of CNVs in TEq7-12w group were irregular in shape involving foveal center, while 67% of CNVs in PRN>12mo group were circular in shape sparing foveal center. Among three groups, statistical difference was found in CNV shape (P = .012) and CNV location (P = .003), while no statistical difference was found in the CNV area (P = .14), vessel density (P = .19), presence of core vessels (P = .23), the presence of small margin loops (P = .20), large margin loops (P = .14), CNV maturity (P = .40), or the mean percentage of choriocapillaris area with flow void (P = .66).

Conclusion: The combination of CNV sparing the foveal center with higher circularity may suggest a clinically inactive CNV following initial anti-VEGF therapy. We found minimal distinguishing OCTA characteristics between those eyes that required ongoing therapy with the treat-and-extend regimen. More research is needed to identify specific CNV characteristics on OCTA that may become a useful tool for the management of NVAMD and timing of treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218889PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592566PMC
February 2020

Eplerenone for the treatment of chronic central serous chorioretinopathy: 3-year clinical experience.

Br J Ophthalmol 2020 02 11;104(2):182-187. Epub 2019 May 11.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA

Background/aims: The efficacy of mineralocorticoid receptor antagonist eplerenone to treat chronic central serous chorioretinopathy (CSCR) has been established. However, previous studies have been limited by small cohort size and short follow-up duration. This study aims to report 3-year clinical outcomes of patients treated with eplerenone for chronic CSCR.

Methods: Institutional review board-approved retrospective chart analysis at a single institution from 2012 to 2018. Baseline best-corrected visual acuity and anatomical measurements related to degree of subretinal fluid (SRF) were collected at eplerenone initiation. Follow-up data were collected at the closest date to 12, 24 and 36 months.

Results: Data were obtained for 100 eyes of 83 patients at 1-year (mean 11.18 ± 4.00 months), 49 eyes at 2-year (24.01 ± 3.33 months) and 33 eyes at 3-year (mean 35.5 ± 7.89 months) follow-up visits. The rate of complete SRF resolution was 31%, 28% and 33%, respectively. At final follow-up, logarithm of the minimum angle of resolution visual acuity change from baseline was +0.10 ± 0.24 (p = 0.130). Average change from baseline at final follow-up for central subfield thickness was -97 ± 140.6 µm (p < 0.001), cube volume was -1.07 ± 1.71 mm (p < 0.001), macular thickness -28. 5 ± 47.5 µm (p < 0.001), maximum SRF height was -95.6 ± 160.5 µm (p < 0.001) and maximum SRF diameter was -1169.0 ± 1638.7 µm (p = 0.008).

Conclusion: Anatomical improvement occurs primarily within the first year of eplerenone treatment for chronic CSCR.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314047DOI Listing
February 2020

Long-Term Assessment of Macular Atrophy in Patients with Age-Related Macular Degeneration Receiving Anti-Vascular Endothelial Growth Factor.

Ophthalmol Retina 2018 06 19;2(6):550-557. Epub 2017 Dec 19.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: Although intravitreal anti-vascular endothelial growth factor (VEGF) injection has become the mainstay treatment for neovascular age-related macular degeneration (nAMD), emerging studies suggest that anti-VEGF may be correlated with the development of macular atrophy (MA) in chronic therapy. The purpose of the current study is to determine the prevalence and progression of MA in nAMD treated with chronic anti-VEGF in a routine clinical practice.

Design: Retrospective cohort.

Participants: Patients with nAMD who were previously treatment-naïve and treated with anti-VEGF at the Cole Eye Institute for at least 4 years.

Methods: This is chart review on anti-VEGF treated patients with nAMD with baseline and yearly follow-up spectral domain-OCT for at least 4 years. Retinal pigment epithelium subillumination analysis was used to automate identification of atrophy. Segmentation errors were manually corrected by 4 expert raters using a standardized grading protocol to quantify MA size. Patient baseline characteristics and treatment course were analyzed to identify predictive factors for the development of MA.

Main Outcome Measures: MA growth rate and prevalence in cohorts with and without baseline atrophy.

Results: A total of 79 eyes from 66 patients (79.8±7.4 years, 63% were female) with nAMD and 4 years of follow-up with anti-VEGF injections were identified. The mean baseline visual acuity was 0.48±0.25 logarithm of the minimum angle of resolution (20/60 Snellen equivalent), and the mean final visual acuity was 0.48±0.49 logarithm of the minimum angle of resolution (20/44 Snellen equivalent, P = 0.23). The average number of injections was 19.8±9.8. MA was observed in 12.7% of eyes at baseline with an average annual growth rate of 0.7±0.5 mm. In eyes without baseline MA, atrophy developed in 53.6% eyes by year 4 with a growth rate of 0.2±0.4 mm per year. Multiple linear regression analysis revealed that the progression of MA was positively correlated with age (R = 0.02, P = 0.009).

Conclusions: More than half of patients with nAMD treated with anti-VEGF injections for 4 years developed new MA. Atrophy progression was most strongly correlated with age, which suggests that baseline disease characteristics may be more predictive of MA progression than cumulative anti-VEGF treatment.
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http://dx.doi.org/10.1016/j.oret.2017.10.010DOI Listing
June 2018

Systemic pharmacokinetic/pharmacodynamic analysis of intravitreal aflibercept injection in patients with retinal diseases.

BMJ Open Ophthalmol 2019 20;4(1):e000185. Epub 2019 Mar 20.

Bayer Pharma, Berlin, Germany.

Objective: Explore relationships between systemic exposure to intravitreal aflibercept injection (IAI) and systemic pharmacodynamic effects via post hoc analyses of clinical trials of IAI for neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DME).

Methods And Analysis: Adults from VGFT-OD-0702.PK (n=6), VGFT-OD-0512 (n= 5), VIEW 2 (n=1204) and VIVID-DME (n=404) studies were included. Validated ELISAs were used to measure concentrations of free and bound aflibercept (reported as adjusted bound) in plasma at predefined time points in each study. Non-compartmental analysis of concentration-time data was obtained with dense sampling in VGFT-OD-0702.PK and VGFT-OD-0512. Sparse sampling was used in VIEW 2 and VIVID-DME. Blood pressure or intrarenal function changes were also investigated.

Results: Following intravitreal administration, free aflibercept plasma concentrations quickly decreased once maximum concentrations were achieved at 1-3 days postdose; pharmacologically inactive adjusted bound aflibercept concentrations increased over a longer period and reached plateau 7 days postdose. Ratios of free and adjusted bound aflibercept decreased over time. There were no meaningful changes in systolic/diastolic blood pressure over the duration of each study at all systemic aflibercept exposure levels. For all treatment arms in VIEW 2, there was no clinically relevant change in mean intrarenal function from baseline at week 52. Overall, incidence of systemic adverse events in VIEW 2 and VIVID-DME was low and consistent with the known safety profile of IAI.

Conclusion: IAI administration was not associated with systemic effects in patients with nAMD or DME as measured by blood pressure or intrarenal function, two known pharmacologically relevant effects of anti-vascular endothelial growth factor.
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http://dx.doi.org/10.1136/bmjophth-2018-000185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440611PMC
March 2019

Ocriplasmin Treatment Leads to Symptomatic Vitreomacular Adhesion/Vitreomacular Traction Resolution in the Real-World Setting: The Phase IV ORBIT Study.

Ophthalmol Retina 2019 01 25;3(1):32-41. Epub 2018 Jul 25.

California Retina Consultants, Santa Barbara, California; California Retina Research Foundation, Santa Barbara, California.

Purpose: To evaluate clinical outcomes and safety up to 12 months after ocriplasmin injection for the treatment of patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction (VMT) in a real-world setting.

Design: The Phase IV Ocriplasmin Research to Better Inform Treatment (ORBIT) trial (NCT02079883) was a Phase IV multicenter, prospective, observational study.

Participants: Patients aged ≥18 years with symptomatic VMA/VMT treated with ocriplasmin.

Methods: Patients received a single 0.125 mg intravitreal injection of ocriplasmin. All assessments and treatment decisions were at the discretion of the treating physician. Spectral-domain OCT (SD-OCT) images were analyzed by an independent central reading center (CRC). All enrolled patients were included in demographic, baseline characteristics, and safety analyses. Patients with symptomatic VMA/VMT at baseline determined by CRC were included in baseline ocular characteristics and efficacy analyses.

Main Outcome Measures: Clinical outcomes were measured up to 12 months and included resolution of symptomatic VMA, closure of full-thickness macular hole (FTMH), mean change from baseline in best-corrected visual acuity (BCVA), incidence of vitrectomy, and time to first vitrectomy. Safety outcomes included the incidence and timing of onset of adverse drug reactions (ADRs).

Results: Of the 539 patients enrolled, 480 were determined to have symptomatic VMA/VMT at baseline post-CRC assessment. After treatment with ocriplasmin, the rate of VMA/VMT resolution was 45.8% (95% confidence interval [CI], 41.3-50.4) at month 1 and 59% (95% CI, 54.4-63.4) at months 10 to 12. The rate of FTMH closure was 30.5% (95% CI, 22.4-39.7) at month 1 and 32.2% (95% CI, 23.9-41.4) at months 10 to 12. Mean (standard deviation) change from baseline in BCVA was 1.5 (11.19) letters at month 1 and 5.2 (13.60) letters at months 10 to 12. Vitrectomy was performed in 28.5% of patients, with a median time to vitrectomy of 63 days. Adverse drug reactions were reported by 30.6% of patients; 5.2% experienced a serious ADR.

Conclusions: Results from the ORBIT study demonstrate that treatment with ocriplasmin is effective and well tolerated in patients with symptomatic VMA/VMT in a real-world setting. The percentage of patients with VMA/VMT resolution at month 1 was higher than previously reported in well-controlled clinical trials. No new safety signals were identified.
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http://dx.doi.org/10.1016/j.oret.2018.07.011DOI Listing
January 2019

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

Ophthalmol Retina 2018 Nov 14;2(11):1107-1117. Epub 2018 Jun 14.

Ophthalmic Imaging Center, Cleveland Clinic, 2022 E 105 St, Cleveland, OH 44106.

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; = 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; = 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.
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http://dx.doi.org/10.1016/j.oret.2018.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335035PMC
November 2018

An efficacy comparison of anti-vascular growth factor agents and laser photocoagulation in diabetic macular edema: a network meta-analysis incorporating individual patient-level data.

BMC Ophthalmol 2018 Dec 27;18(1):340. Epub 2018 Dec 27.

Cole Eye Institute, Cleveland, OH, USA.

Background: This was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laser photocoagulation in patients with diabetic macular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment.

Methods: An updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2 mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5 mg as-needed (PRN), ranibizumab 0.5 mg treat-and-extend (T&E), and laser photocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with ≥10 and ≥ 15 ETDRS letter gains/losses at 12 months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network).

Results: Thirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90-8.52 ETDRS letters), ≥15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12-4.20), and ≥10 ETDRS letter loss (OR 0.25, 95% CrI 0.05-0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26-10.61 ETDRS letters) (IPD and aggregate random-effects model).

Conclusions: This NMA, which incorporated IPD to improve analytic robustness, showed evidence of superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5 mg PRN. These results were irrespective of adjustment for baseline BCVA.
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http://dx.doi.org/10.1186/s12886-018-1006-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307247PMC
December 2018

Surgical Repair of Traumatic Macular Holes With Extreme Macular Pathology Using an Internal Limiting Membrane Flap Technique.

Ophthalmic Surg Lasers Imaging Retina 2018 10;49(10):e143-e146

This report describes the use of inverted internal limiting membrane (ILM) flap technique as a treatment option for traumatic macular holes (MHs) with severe macular pathology. An interventional case series of two patients who experienced blunt trauma is reported. One patient developed two adjacent MHs and the second patient a MH with focal tissue avulsion in the fovea. Each patient underwent pars plana vitrectomy with ILM flap creation and intraocular gas tamponade. The ILM flap technique was successfully used for closure of MHs in one patient with a traumatic double MH and another patient with MH with foveal tissue avulsion. Visual acuity and symptoms improved in both patients. The ILM flap technique is a useful option for patients even with advanced pathologic findings subsequent to traumatic MH formation. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e143-e146.].
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http://dx.doi.org/10.3928/23258160-20181002-17DOI Listing
October 2018

Budget impact analysis of ocriplasmin for the treatment of symptomatic vitreomacular adhesion in the USA.

J Comp Eff Res 2018 12 23;7(12):1195-1207. Epub 2018 Oct 23.

Navigant Consulting, Inc., 101 California Street, Suite 4100, San Francisco, CA 94111, USA.

Background: Vitreomacular traction (VMT) treatment options include watchful waiting, vitrectomy and intravitreal ocriplasmin injection (Jetrea). This analysis used results from the recently completed OASIS randomized clinical trial to evaluate the 2-year budget impact of ocriplasmin injection availability for treatment of Stage I or II VMT without epiretinal membrane formation in a modeled US health plan.

Materials & Methods: VMT prevalence, treatment patterns and disease resolution rates were from literature, a US retinal-specialist survey and the OASIS trial. Medicare payment rates were applied and a national scenario analysis was conducted.

Results: With ocriplasmin available, vitrectomy use and complications-related costs decreased. Budget impact of ocriplasmin to the health plan was US$143,599 over 2 years or US$0.0060 per-member per-month.

Conclusion: Ocriplasmin was projected to be minimally cost-additive at US$0.0060 per-member per-month over 2 years.
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http://dx.doi.org/10.2217/cer-2018-0057DOI Listing
December 2018

The Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration (DREAM) study: an open-label phase II trial.

Br J Clin Pharmacol 2019 02 25;85(2):347-355. Epub 2018 Nov 25.

Bayer AG, Division Pharma, Berlin and Wuppertal, Germany.

Aims: This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD).

Methods: Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml ) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best-corrected visual acuity (BCVA) from baseline to weeks 4 and 12.

Results: In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) -0.61, 2.97] and -2.4 (90% CI -4.18, -0.54) letters at weeks 4 and 12, respectively. Ocular treatment-emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab).

Conclusions: The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).
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http://dx.doi.org/10.1111/bcp.13794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339971PMC
February 2019

Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study.

Am J Ophthalmol 2019 01 24;197:156-167. Epub 2018 Aug 24.

Department of Ophthalmology, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China. Electronic address:

Purpose: Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5 mg conbercept, a new anti-vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients.

Design: A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial.

Methods: Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group.

Intervention: The conbercept group received intravitreal injections of conbercept (0.5 mg) once monthly for the first 3 months, then once quarterly until month 12 (3 + Q3M). The sham group received first 3 monthly sham injections and then 3 monthly injections of conbercept (0.5 mg) followed by quarterly administrations until month 12.

Main Outcome Measures: The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3.

Results: A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were +9.20 letters in the conbercept group and +2.02 letters in the sham group, respectively (P < .001). At 12 months, the mean changes from baseline in BCVA letter score were +9.98 letters in the conbercept group and +8.81 letters in the sham group (P = .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure.

Conclusions: A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.
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http://dx.doi.org/10.1016/j.ajo.2018.08.026DOI Listing
January 2019

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

Ophthalmol Retina 2018 Jun;2(6):606-612

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

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 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. Cohen's 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.
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http://dx.doi.org/10.1016/j.oret.2017.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053057PMC
June 2018

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

Ophthalmol Retina 2018 Apr;2(4):263-267

Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.

Purpose: To assess the retinal architecture changes which occur during epiretinal membrane (ERM) surgery, utilizing intraoperative optical coherence tomography (OCT).

Design: Prospective multi-surgeon single center study.

Subjects/participants: Subjects from the PIONEER OCT 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). OCT 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: OCT-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.
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http://dx.doi.org/10.1016/j.oret.2017.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891156PMC
April 2018

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

Ophthalmology 2018 07 2;125(7):1014-1027. Epub 2018 Mar 2.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

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.
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http://dx.doi.org/10.1016/j.ophtha.2017.12.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015779PMC
July 2018