Fabiana Q. Silva

A single-arm, investigator-initiated study of the efficacy, safety, and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration previously treated with ranibizumab or bevacizumab (ASSESS study): 12-month analysis.

Summary statement In subjects with active exudative age-related macular degeneration, treating with a fixed intravitreal aflibercept injection dosing regimen for 12 months demonstrated improved anatomic and vision endpoints from baseline. Purpose Switching therapies in neovascular age-related macular degeneration (AMD) may offer an advantage for some patients. This study evaluates the efficacy of intravitreal aflibercept injection (IAI) in subjects previously treated with ranibizumab and/or bevacizumab. Methods Subjects (n=26) were given monthly 2 mg of IAI for 3 months, followed by 2 mg once in every 2 months for up to 12 months. The mean absolute change from baseline in central subfield thickness (CST) measured by optical coherence tomography and the mean change from baseline in best-corrected visual acuity (BCVA) early treatment in diabetic retinopathy study (ETDRS) letter score were obtained. Additionally, the percentage of subjects who gained or lost ≥15 letters of vision and the percentage of subjects who are 20/40 or better or 20/200 or worse were evaluated. Results There was a mean decrease in CST of −50.3 μm (P<0.001) and a mean increase in ETDRS BCVA of +9.2 letters (P<0.001). Twenty-seven percent of subjects experienced a ≥15-letter improvement in visual acuity, and no subject lost ≥3 lines of vision from baseline. Fifty percent of subjects were 20/40 or better, and 11.5% of subjects were 20/200 or worse at month 12. Conclusion Fixed IAI dosing regimen for 12 months demonstrated improved anatomic and vision endpoints in subjects with active exudative AMD.

Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice

Aim To determine the impact of initial visual acuity (VA) on anti-vascular endothelial growth factor (VEGF) treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice. Methods A retrospective study was conducted at a single academic institution to identify 177 treatment naïve patients with macular oedema secondary to branch retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO) and central retinal vein occlusion (CRVO) treated with intravitreal anti-VEGFs. Exclusion criteria included prior intravitreal injection or presence of active confounding ocular disease. Patients were stratified by initial VA; main outcomes measured were average change in VA and mean absolute change in central subfield thickness (CST) at 6 and 12 months. Results Patients with BRVO with initial VA of 20/40 or better had no significant changes in average letters gained and CST from baseline (+2.6 letters, p=0.42; −48.94 µm, p=0.12) compared with patients with initial VA between 20/50 and 20/300 (+13.2 letters, p<0.001; −98.20 µm, p<0.001) after 12 months. Patients with CRVO/HRVO with initial VA of 20/320 or worse had the most improvement in average letters gained and CST from baseline (+42.2 letters, p<0.001; −182.84 µm, p=0.004) with anti-VEGF therapy compared with patients with initial VA between 20/50 and 20/300 (+9.4 letters, p=0.016; −160.87 µm, p<0.001) and patients with initial VA of 20/40 or better (−9.6 letters, p=0.14; −47.92 µm, p=0.38). Conclusions For macular oedema secondary to retinal vein occlusion, anti-VEGF treatment can result in a greater improvement in average letters gained and in CST for those with poor initial VA compared with those with better initial VA.

Association of Disorganization of Retinal Inner Layers With Visual Acuity Response to Anti–Vascular Endothelial Growth Factor Therapy for Macular Edema Secondary to Retinal Vein Occlusion

Importance Disorganization of retinal inner layers (DRIL) has demonstrated significant correlations with visual acuity (VA) in center-involved diabetic macular edema. In patients with retinal vein occlusion (RVO) and secondary macular edema, DRIL may be a useful biomarker in determining VA outcomes. Objective To examine whether DRIL at baseline and after treatment is associated with VA in RVO. Design, Setting, and Participants A retrospective review of records of 147 patients 18 years or older with treatment-naive branch RVO (BRVO), central RVO (CRVO), or hemispheric RVO (HRVO), with a minimum of 12 months of follow-up, who presented to a tertiary ophthalmic center from December 1, 2010, to January 1, 2016, was conducted. Data collection continued through January 2017. Exclusion criteria included active confounding retinal or ocular disease, history of pars plana vitrectomy, or prior intravitreal injections. Two masked graders calculated a DRIL score based on DRIL presence in 3 predefined regions on spectral-domain optical coherence tomography at baseline, 6 months, and 12 months. A third masked grader was used for discrepancies. Exposures Anti–vascular endothelial growth factor (AVF) therapy (ranibizumab, aflibercept, or bevacizumab) determined by the treating physician. Main Outcomes and Measures The DRIL score at baseline for determining VA outcomes and correlation of VA with changes in DRIL burden in response to AVF therapy. Results In the 147 patients (mean [SD] age, 68.9 [13.1] years; 75 [51.0%] female), baseline DRIL was seen in 91 eyes (61.9%). In the BRVO group but not the CRVO group, baseline DRIL was associated with lower baseline Early Treatment Diabetic Retinopathy Study (ETDRS) score (score of 66.7 for no DRIL vs 54.6 for DRIL, P = .002). Absence of DRIL at baseline in the CRVO/HRVO group correlated with greater VA gains at 6 months, adjusting for baseline VA (score change of 19.50 for no DRIL vs 12.72 for DRIL; P = .04). During 12 months, continued DRIL presence in BRVO was associated with less VA gain up to 6 months (score change of 6.2 for the DRIL increase group vs 18.6 for the DRIL decrease group vs 2.9 for the DRIL stable group; P = .02). Increasing DRIL scores in CRVO/HRVO were associated with reduced VA improvement at 6 months (score change of –0.12 for the DRIL increase group vs 16.90 for the DRIL decrease group vs 8.45 for the DRIL stable group; P = .002) and 12 months (score change of –1.91 for the DRIL increase group vs 17.83 for the DRIL decrease group vs 6.97 for the DRIL stable group; P < .001). Conclusions and Relevance Baseline DRIL presence and DRIL burden changes with AVF therapy for macular edema secondary to RVO may be useful biomarkers of ETDRS score improvements.

Comparison of ranibizumab and bevacizumab for macular edema secondary to retinal vein occlusions in routine clinical practice

BACKGROUND AND OBJECTIVE To determine outcomes of intravitreal ranibizumab (IVR) (Lucentis; Genentech, South San Francisco, CA) versus bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA) for treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) in routine clinical practice. PATIENTS AND METHODS A retrospective study identified treatment-naïve patients with ME secondary to RVO where treatment with either IVB or IVR was initiated. Retreatment criteria were based on ophthalmic examination and/or spectral-domain optical coherence tomography findings. RESULTS Central RVO/hemi-RVO cohort: At 12 months, change in visual acuity (VA) (IVR: +12.9 letters, IVB +6.9 letters; P = .53), central subfield thickness (CST) (IVR: -144.1 μm, IVB: -153.9 μm; P = .88), and number of injections (IVR: 5.40 injections, IVB: 5.64 injections; P = .70) were not different between groups. Branch RVO cohort: At 12-month follow-up, no differences in change in VA (IVR: +15.2 letters, IVB: +10.6 letters; P = .46), CST (IVR: -23.1 μm, IVB: -91.4 μm; P = .16), or number of injections (IVR: 5.93 injections, IVB: 5.13 injections; P = .15) were noted. CONCLUSION There is no notable difference in outcome between IVR and IVB when treating ME from RVO in routine clinical practice. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:465-472.].

A retrospective study of the influence of the vitreomacular interface on macular oedema secondary to retinal vein occlusion

Aims To compare anti-vascular endothelial growth factor (VEGF) treatment outcomes for macular oedema (ME) secondary to retinal vein occlusion (RVO) based on vitreoretinal interface (VRI) status. Methods This retrospective case series includes treatment-naive eyes diagnosed with RVO and treated with anti-VEGF injections. Eyes were stratified based on international VRI classification schema at baseline into three groups—vitreomacular traction (group A), no posterior vitreous detachment (PVD) (group B) and PVD without vitreomacular attachment (group C). Fifty-two eyes were identified based on inclusion/exclusion criteria. The primary endpoint was change in central subfield thickness (CST) on optical coherence tomography at 6 months. Results There were no statistically significant differences in baseline characteristics of patients with RVO when stratified by VRI subgroups. After 6 months of treatment, there was no statistically significant difference in the change in CST from baseline between VRI cohorts (p=0.11). There was a trend demonstrating the greatest improvement in CST in eyes in group A compared with eyes in groups B and C (−224.13 μm, −160.88 μm and −50.92 μm, respectively, p=0.11 between cohorts). Mean change in logarithm of the minimum angle of resolution visual acuity from baseline to month 6 in group A compared with groups B and C was −0.25, −0.14 and −0.13, respectively (p=0.64 between cohorts). Conclusions We did not identify an association between VRI status and treatment outcomes with anti-VEGF agents for ME secondary to RVO.

The Prevalence of Adverse Ocular Hemorrhagic Events in Patients Utilizing Oral Anticoagulant and Antiplatelet Therapy in Routine Clinical Practice

BACKGROUND AND OBJECTIVE Previous literature assessing ocular hemorrhagic complications of anticoagulant/antiplatelet medications in routine clinical practice is limited. This study evaluates the prevalence of spontaneous ocular hemorrhagic events associated with anticoagulation/antiplatelet therapy. PATIENTS AND METHODS A retrospective study was performed to identify patients taking anticoagulants (rivaroxaban [Xarelto; Janssen Pharmaceuticals, Beerse, Belgium], bivalirudin [Angiomax; The Medicines Company, Parsippany, NJ], lepirudin [Refludan; Bayer HealthCare Pharmaceuticals, Berlin, Germany], dabigatran [Pradaxa; Boehringer Ingelheim, Ingelheim am Rhein, Germany], and argatroban) and antiplatelet agents (clopidogrel [Plavix; Bristol-Myers Squibb, New York City, NY], prasugrel [Effient; Lilly Medical, Indianapolis, IN], and ticagrelor [Brilinta; AstraZeneca, Cambridge, UK]) who presented for an eye examination. Location of hemorrhage, relevant systemic and ocular comorbidities, baseline demographics, and concomitant aspirin use were noted. RESULTS A total of 44 patients with spontaneous ocular hemorrhage were identified. Thirty patients had a single episode, whereas 14 patients had multiple episodes (two or more hemorrhagic events). Prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%). CONCLUSION Prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:27-34.].

36-Month Evaluation of Intravitreous Aflibercept Injection for Wet Age-Related Macular Degeneration in Patients Previously Treated With Ranibizumab or Bevacizumab

BACKGROUND AND OBJECTIVE In the ASSESS study, patients with neovascular age-related macular degeneration transitioned from other anti-vascular endothelial growth factor therapies to intravitreous aflibercept (Eylea; Regeneron, Tarrytown, NY) injections (IAI). The purpose was to determine the 36-month outcomes following the change from a fixed 24-month IAI dosing regimen to a routine clinical practice regimen. PATIENTS AND METHODS Patients were treated with a fixed bimonthly regimen for the first 2 years. In the third year, patients were managed according to routine clinical practice. RESULTS A total of 18 patients completed the 36 months and were considered for statistical analyses. At 36 months, a nonsignificant decrease of -37.8 μm in central subfield thickness and a nonsignificant gain of 5.8 letters from baseline were observed. CONCLUSION Despite the significant visual and anatomical gains observed in the 2 years of fixed-dosing IAI, there was gradual decline in these improvements when patients were transitioned to a variable regimen. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:179-185.].

Non-Mydriatic Ultra-Widefield Imaging Compared With Single-Field Imaging in the Evaluation of Peripheral Retinal Pathology

BACKGROUND AND OBJECTIVE To report clinical feasibility of non-mydriatic ultra-widefield (NMUWF) imaging and determine the prevalence of peripheral retinal pathology in comparison to standard single-field imaging in a primary care setting. PATIENTS AND METHODS Six hundred and thirty-two subjects (1,260 eyes) who underwent NMUWF imaging during annual health screening from October 2015 through March 2016 were retrospectively identified. An automated algorithm processed the raw images into: (1) NMUWF image with mask/grid outline that delineates the center 45° field simulating standard single-field photograph and (2) single-field image comprising 45° posterior pole extracted from the corresponding NMUWF image. RESULTS Mean age of patients was 59.6 years ± 7.5 years. Of the 1,260 eyes, 1,238 eyes (98.3%) were considered optimum for grading. NMUWF images detected peripheral retinal pathology in 228 eyes (18.4%) that were not visible on corresponding single-field images. CONCLUSIONS NMUWF imaging is feasible in a primary care setting, allows improved visualization of peripheral retinal pathology, and may therefore be useful for telemedicine screening. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:962-968.].

Long-Term Outcomes of Anti-VEGF Therapy in Patients With Macular Edema Secondary to Retinal Vein Occlusion:

Purpose: To evaluate long-term visual and anatomical outcomes of anti–vascular endothelial growth factor (VEGF) therapy for macular edema (ME) secondary to retinal vein occlusion (RVO) in routine clinical practice. Methods: Patients with ME secondary to hemi-RVO (HRVO), central RVO (CRVO), or branch RVO (BRVO) after initiating anti-VEGF therapy were followed for at least 36 months. Main outcomes were change in best visual acuity (BVA) and mean absolute change in central subfield thickness (CST) at 12, 24, 36, and 48 months. Results: Patients with BRVO showed significant increases in BVA that were maintained after 12, 24, 36, and 48 months (+11.03, +12.06, +10.71, and +9.26 letters, respectively; P < .05). CST significantly decreased after 12, 24, 36, and 48 months (−83.51, −67.93, −97.52, −127.85 µm, respectively; P < .05). In patients with CRVO/HRVO, significant improvements in BVA were seen at 12 and 24 months (+9.39 and +8.54 letters, respectively; P = .023). At 36 and 48 months, the visual gain was not significant (+2.64 and +3.42 letters, respectively; P > .05). For CST changes, there were significant decreases at 12, 24, and 36 months (−146.23, −149.54, and −166.44 µm, respectively; P < .05). At 48 months (−97.66 µm, P = .130), changes in CST were not significant. Conclusions: In routine clinical practice, visual and anatomical benefits of anti-VEGF agents in patients with BRVO were sustained at 36 and 48 months. For patients with CRVO/HRVO, anatomical improvements were maintained for 36, but not 48 months, while visual improvements were no longer maintained by 36 months.

Evaluation and Referral of Diabetic Eye Disease in the Endocrinology and Primary Care Office Settings

BACKGROUND AND OBJECTIVE The purpose of this study was to identify whether endocrinologists and primary care physicians (PCP) adequately screen for ophthalmic symptoms/signs within office visits and provide timely ophthalmology referrals in patients with diabetes. PATIENTS AND METHODS Patients between the ages of 18 years and 80 years with diabetes who underwent an office visit with an endocrinologist or a PCP between January 1, 2014, and December 31, 2014, were identified. Demographics, ophthalmic assessments, and referral information were collected. RESULTS A total of 1,250 patient records were reviewed. Providers asked about ophthalmic symptoms/signs in 95.5% and 71% of endocrinology and primary care office encounters, respectively (P < .0001). Past and/or future ophthalmology appointments were verified in 86.1% and 49.7% of patients during endocrinology and PCP visits, respectively (P < .0001). CONCLUSIONS Ophthalmic complications from diabetes are not adequately screened, especially within the primary care setting, and further quality improvement measures may improve adherence to recommended screening protocols. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:930-934.].