Amy Babiuch

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.

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

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

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.].

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

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

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.