KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema.

PURPOSE: To report the 100-week outcomes from the KESTREL and KITE trials. DESIGN: Two phase 3, double-masked, active-controlled, randomized trials. METHODS: Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N = 566) or 1:1 to BRO6 or AFL in KITE (N = 360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. RESULTS: At week 100, change from baseline in BCVA (letters) was +8.8 for BRO6 and +10.6 for AFL in KESTREL; and +10.9 for BRO6 and +8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid than AFL subjects. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE), of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. CONCLUSIONS: Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through year 2.

Anti-vascular endothelial growth factor dosing frequency and visual outcomes in macular oedema following branch retinal vein occlusion.

OBJECTIVES: To determine the relationship between treatment frequency with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes in eyes with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) in US clinical practice. METHODS: Study eyes that initiated anti-VEGF injections between January 2012 and May 2016 were followed for ≥1 year in a retrospective analysis of medical records (Vestrum Health database). Eyes were analysed in 2 cohorts by treatment duration (years 1 and 2) and then in 2 subcohorts by injection frequency (≤6 or ≥7 injections/year). RESULTS: Among 3099 eyes with MO secondary to BRVO, 1197 (38.6%) received ≤6 injections (mean injections, 4.6; baseline mean VA, 53 letters) and 1902 (61.4%) received ≥7 injections through 1 year (mean injections, 8.8; baseline mean VA, 52 letters). At year 1, mean VA gain from baseline was 10.4 versus 13.9 letters in eyes receiving ≤6 versus ≥7 injections (p < 0.001). At year 2, mean VA in eyes receiving ≤6 (n = 42) versus ≥7 injections (n = 227) was 64 versus 68 letters, respectively (p = 0.19). Mean VA change between the start and end of year 2 in eyes receiving ≥7 injections in year 1 and ≤6 in year 2 differed significantly from that of eyes receiving ≥7 injections in both years (-3.0 vs 0.7 letters, respectively; p < 0.001). CONCLUSIONS: In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with MO secondary to BRVO.

INCIDENCE OF NEW DIABETIC MACULAR EDEMA IN FELLOW EYES OF PATIENTS IN THE VISTA AND VIVID STUDIES.

PURPOSE: To characterize diabetic macular edema (DME) incidence in fellow eyes of patients treated for DME in the study eye. METHODS: This post hoc analysis of VISTA/VIVID data evaluated fellow eyes without DME at baseline through Week 100. Diabetic macular edema presence in the fellow eye was inferred by investigator-reported DME adverse events and use of DME treatments. RESULTS: Over 100 weeks, 44.9%, 44.2%, and 42.9% of fellow eyes developed DME in the intravitreal aflibercept injection 2 mg every 4 weeks (n = 245), intravitreal aflibercept injection 2 mg every 8 weeks (n = 258), and laser control (n = 252) groups, respectively. Mean time to DME development in combined treatment groups was ∼6 months. Multivariable regression analysis confirmed patients with shorter diabetes duration (hazard ratio per 10-year decrease, 1.16; 95% confidence interval, 1.03-1.30; P = 0.0160) and thicker baseline study eye central subfield thickness (hazard ratio per 10- µ m increase, 1.01; 95% confidence interval, 1.01-1.02; P = 0.0002) were at higher risk of developing DME in the fellow eye. CONCLUSION: Among patients with DME in one eye at baseline, almost half developed DME in the fellow eye over 2 years. Shorter duration of diabetes and thicker study eye central subfield thickness were predictors of DME development in the fellow eye.

Functional outcomes of sustained improvement on Diabetic Retinopathy Severity Scale with intravitreal aflibercept in the VISTA and VIVID trials.

AIMS: To assess time to, cumulative incidence of, and functional benefit of achieving sustained ≥2-step Diabetic Retinopathy Severity Scale (DRSS) improvement in diabetic macular oedema (DMO). METHODS: Post hoc analysis of VISTA/VIVID including eyes with DMO treated with intravitreal aflibercept injections (IAI), 2 mg q4 weeks (2q4, n = 250) or q8 weeks after 5 monthly doses (2q8, n = 249), or laser control (n = 249). Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated in sustained (≥2 consecutive visits) DRSS subgroups (≥1-step worsening, no change, ≥2-step improvement). RESULTS: Time to sustained ≥2-step DRSS improvement was shorter for both the IAI 2q4 and IAI 2q8 groups versus laser (both log-rank p < 0.001). Cumulative incidences of sustained ≥2-step DRSS improvement with IAI 2q4 and IAI 2q8 versus laser were 40.0% and 42.8% versus 15.5% (both p < 0.001) through week 100. Mean differences (95% CI) in BCVA gains from baseline at weeks 52 and 100 between eyes with sustained ≥2-step DRSS improvement versus sustained ≥1-step DRSS worsening were -3.0 (-8.9, 2.9) and 6.2 (0.2, 12.2) letters with laser, and 4.2 (0.8, 7.6) and 4.9 (1.3, 8.4) letters with IAI combined, respectively. Difference (95% CI) in CST reduction was significantly greater only with IAI combined at week 100 (-83.0 [-140.8, -25.3]). Correlations between BCVA and CST changes were weak. CONCLUSIONS: DMO eyes treated with IAI achieved sustained ≥2-step DRSS improvement significantly earlier and more frequently versus laser. This improvement was associated with greater BCVA gains, independent of CST reductions. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifiers: NCT01363440 and NCT01331681 .

KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema.

PURPOSE: To compare the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema (DME). DESIGN: Double-masked, 100-week, multicenter, active-controlled, randomized trials. METHODS: Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (n = 566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n = 360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by 12-week (q12w) dosing, with optional adjustment to every 8 weeks (q8w) if disease activity was identified at predefined assessment visits; aflibercept groups received 5 doses every 4 weeks (q4w) followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity (BCVA) change from baseline at Week 52; secondary endpoints included the proportion of subjects maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale score, and anatomical and safety outcomes. RESULTS: At Week 52, brolucizumab 6 mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 letters vs +9.4 letters; P < .001), more subjects achieved central subfield thickness (CSFT) <280 µm, and fewer had persisting subretinal and/or intraretinal fluid vs aflibercept, with more than half of brolucizumab 6 mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6 mg showed superior improvements in change of CSFT from baseline over Week 40 to Week 52 vs aflibercept (P = .001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE. CONCLUSION: Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME.

Rates of Suspected Endophthalmitis Following Intravitreal Injections in Clinical Practices in the United States.

BACKGROUND AND OBJECTIVE: To evaluate rates of suspected endophthalmitis following intravitreal injections of aflibercept, bevacizumab, ranibizumab (vial and pre-filled), dexamethasone implant, and triamcinolone in clinical practice. PATIENTS AND METHODS: Retrospective study of aggregated electronic medical records from the Vestrum Health Database. Eyes with a diagnosis of suspected endophthalmitis based on billing codes between January 2013 and June 2019 were included. RESULTS: Total number of injections, suspected endophthalmitis cases, and medication rate, respectively, were: aflibercept (1,412,699; 687; 0.049%); bevacizumab (1,467,722; 379; 0.026%); ranibizumab vial (884,061; 233; 0.026%), ranibizumab pre-filled (427,763; 96; 0.022%); dexamethasone implant (49,464; 53; 0.107%); and triamcinolone (75,038; 110; 0.147%). Rates were lower for bevacizumab and ranibizumab (vial and pre-filled) compared to aflibercept, dexamethasone implant, and triamcinolone (P < .05). Triamcinolone had a higher rate compared to all of the other medications (P < .05). CONCLUSIONS: Suspected endophthalmitis rates following anti-vascular endothelial growth factor injections in clinical practice were similar to reported rates in clinical trials. Rates of suspected endophthalmitis following steroid injections trended higher with significantly higher rates with triamcinolone. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:312-318.].

Effect of Baseline Subretinal Fluid on Treatment Outcomes in VIVID-DME and VISTA-DME Studies.

PURPOSE: To evaluate the effect of baseline subretinal fluid (SRF) on treatment outcomes with intravitreal aflibercept injection (IAI) versus laser treatment in patients with diabetic macular edema (DME) in the VIVID and VISTA studies. DESIGN: Post hoc analysis of 2 randomized controlled trials. PARTICIPANTS: Eight hundred seventy-two patients with DME. METHODS: We randomized patients to receive IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser. MAIN OUTCOME MEASURES: Effect of presence or absence of baseline SRF on visual outcomes in the integrated dataset at weeks 52 and 100. RESULTS: Mean best-corrected visual acuity (BCVA) gains in the 2q4, 2q8, and laser arms at week 52 were +14.5, +11.0, and -2.3 letters, respectively, (those with baseline SRF) and +10.3, +10.6, and +2.5 letters, respectively, (those without). At week 100, mean gains were +13.5, +10.9, and -2.3 letters (those with baseline SRF) and +10.6, +10.0, and +2.7 letters (those without). The treatment effect for IAI versus laser from baseline to week 52 of 100 was greater for patients with baseline SRF versus those without (nominal P < 0.001, for interaction). The proportions of patients who gained 15 letters or more in the 2q4, 2q8, and laser arms at week 52 were 52.3%, 40.2%, and 8.9%, respectively, (those with baseline SRF) and 30.9%, 29.1%, and 8.2%, respectively, (those without) and at week 100 were 50.0%, 35.4%, and 12.9%, respectively, (those with baseline SRF) and 33.3%, 30.5%, and 12.5%, respectively, (those without). Time to first sustained SRF clearance seemed to be shorter in the IAI arms versus laser. The overall safety profile was similar in the IAI arms. CONCLUSIONS: This post hoc analysis demonstrated the visual outcome benefits of IAI over laser, regardless of baseline SRF status. A greater treatment effect of IAI was observed in patients with baseline SRF versus those without; however, no meaningful impact of baseline SRF status on treatment outcomes with IAI was demonstrated, indicating that the differential effects of laser might have been the driving force behind the different treatment outcomes in both groups.

Longitudinal Retinal Perfusion Status in Eyes with Diabetic Macular Edema Receiving Intravitreal Aflibercept or Laser in VISTA Study.

PURPOSE: To evaluate changes in retinal perfusion status with intravitreal aflibercept injection (IAI) and laser treatment in the phase 3 VISTA study of patients with diabetic macular edema (DME). DESIGN: Post hoc analysis of a double-masked, randomized, active-controlled, phase 3 trial. PARTICIPANTS: Patients with center-involved DME in the study eye. METHODS: VISTA randomized 466 patients to laser, IAI 2 mg every 4 weeks (2q4), or IAI 2 mg every 8 weeks after 5 monthly doses (2q8). One eye per patient was enrolled in the study. Retinal perfusion status was evaluated by fluorescein angiography based on the presence or absence of retinal nonperfusion (RNP) in quadrants intersecting at the optic nerve head by a masked independent reading center at weeks 24, 52, 72, and 100. Visual and anatomic outcomes were evaluated at all visits. In patients who received rescue treatment, data were censored from the time rescue treatment was given. MAIN OUTCOME MEASURES: Change in perfusion status from baseline through week 100. RESULTS: At week 100, the proportion of eyes with improvement in retinal perfusion (defined as a reduction from baseline in the total number of quadrants in which RNP is present) in the laser control, 2q4, and 2q8 groups was 14.6%, 44.7%, and 40.0%, respectively. The proportion of eyes that experienced worsening in retinal perfusion (defined as an increase from baseline in the total number of quadrants in which RNP is present) at week 100 in the laser control, 2q4, and 2q8 groups was 25.0%, 9.0%, and 8.6%, respectively. CONCLUSION: Post hoc analysis of the phase 3 VISTA study in patients with DME provides evidence that regular IAI dosing not only can slow worsening of retinal perfusion associated with diabetic retinopathy but also may be able to improve retinal perfusion in some cases by decreasing zones of RNP.

Factors Associated With Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema With Anti-Vascular Endothelial Growth Factor Therapy: An Exploratory Analysis of the Protocol T Randomized Clinical Trial.

Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial , Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95% CI, -3.0 to -1.2; P < .001) in the VA and 1.9 letters (95% CI, -2.4 to -1.3; P < .001) in the VA AUC analyses. For each 1% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95% CI, -1.5 to -0.5; P < .001) and 0.5 letters (95% CI, -0.9 to -0.2; P < .001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95% CI, 0.9-5.4; P = .007) and VA AUC (95% CI, 1.3-4.2; P < .001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 µm, P = .01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 µm, P = .01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.

LARGE SILICONE DROPLETS AFTER INTRAVITREAL BEVACIZUMAB (AVASTIN).

PURPOSE: Despite its off-label status, intravitreal bevacizumab is the most commonly used intraocular anti-vascular endothelial growth factor agent. Regulation of compounding pharmacies has recently increased to make compounded pharmaceuticals safer. Despite these changes, a marked increase in symptomatic, large silicone oil droplets following intravitreal bevacizumab injections was noticed. METHODS: Retrospective chart review was performed. Within a single private practice, patients who were noted to have large or symptomatic silicone oil bubbles after an intravitreal injection were reviewed. RESULTS: A recent, dramatic increase in the incidence of large or symptomatic silicone oil droplets was noted, with 23 cases noted in the past 5 months, compared with 1 in the previous decade. Patients frequently noted a circular floater consisting of a dark ring surrounding a bright central area immediately following an injection of intravitreal bevacizumab. All bevacizumab injections were from single-piece insulin syringes. B-scan ultrasonography produced a very characteristic reverberation pattern. No inflammation or visual acuity loss was noted because of the droplets; however, some patients were annoyed enough to consider vitrectomy. CONCLUSION: Patients should be carefully evaluated for this possibility, and the characteristic symptom of a round floater consisting of a dark ring surrounding a bright center, and the prominent reverberation pattern on B-scan ultrasonography may help increase detection. Changes in consent forms and discussion of this possibility are indicated while investigation into the cause of this increased incidence continues, especially if one is administering bevacizumab via the one-piece insulin syringes commonly used by compound pharmacies.

When and How to Incorporate Steroids for Persistent Diabetic Macular Edema: A Discussion of Real-World Treatment Optimization Strategies.

In the United States, diabetic macular edema (DME) is the leading cause of vision loss among people with diabetic retinopathy. Despite the availability of different therapies for DME, up to half of patients with DME show some persistent edema after anti-vascular endothelial growth factor (VEGF) treatment alone, leaving these patients at high risk for vision loss. However, dosing in a similar fashion to that of pivotal anti-VEGF trials is difficult because of real-life challenges faced in clinical practice. This is particularly true for DME, in that the frequency and burden of anti-VEGF injections are a major challenge to patient care. Research evaluating anti-VEGF therapies has shaped the treatment paradigms for patients with DME, and similar benefits have also been noted in clinical trials evaluating the use of intravitreal steroids. Treatment with a long-term intravitreal corticosteroid, which requires fewer injections than treatment with most short-acting therapies, has been found to reduce inflammation and improve vision in a percentage of patients. This roundtable discussion, which took place during the 2018 annual meeting of the Vit-Buckle Society, reviews the current treatment paradigms for DME and evaluates how to customize and optimize treatment strategies geared toward individualized patient care. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S15.].

Baseline Factors Affecting Changes in Diabetic Retinopathy Severity Scale Score After Intravitreal Aflibercept or Laser for Diabetic Macular Edema: Post Hoc Analyses from VISTA and VIVID.

PURPOSE: To evaluate whether select baseline systemic and ocular factors influence ≥2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) score at week 100 in VISTA and VIVID. DESIGN: Post hoc analysis of 2 similarly designed phase 3 trials, VISTA and VIVID. PARTICIPANTS: Total of 456 patients with center-involved diabetic macular edema (DME). METHODS: VISTA and VIVID randomized 872 DME patients to receive intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation. This post hoc analysis evaluated the influence of select baseline factors on ≥2-step DRSS score improvement by logistic regression in an integrated VISTA and VIVID dataset using observed cases (n = 456) with patients in each treatment group divided into tertiles based on each characteristic. MAIN OUTCOME MEASURES: Proportion of patients with ≥2-step improvement in DRSS score from baseline at week 100 by age, duration of diabetes, hemoglobin A1c (HbA1c), body mass index (BMI), best-corrected visual acuity (BCVA), central subfield thickness (CST), and DRSS score. RESULTS: At week 100, 10.1%, 34.3%, and 37.6% of patients in the laser, 2q4, and 2q8 groups experienced a ≥2-step DRSS score improvement, respectively. Age, duration of diabetes, HbA1c, BMI, BCVA, and CST had no impact on the ability to achieve ≥2-step improvement in DRSS score. Initial DRSS score was the only factor significantly associated with ≥2-step DRSS score improvement in all treatment groups at weeks 24, 52, 76, and 100. Relatively higher proportions of IAI-treated patients with worse BCVA or thicker CST experienced ≥2-step DRSS score improvement compared with those with better BCVA or thinner CST, respectively, but these associations were not statistically significant. CONCLUSION: A strong association was present between baseline DRSS score and ≥2-step DRSS score improvement at week 100 for DME patients in VISTA and VIVID.

SYSTEMIC PHARMACOKINETICS AND PHARMACODYNAMICS OF INTRAVITREAL AFLIBERCEPT, BEVACIZUMAB, AND RANIBIZUMAB.

PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of aflibercept, bevacizumab, and ranibizumab in patients with neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO). METHODS: Prospective, open-label, nonrandomized clinical trial of patients with AMD, DME, or RVO who were antivascular endothelial growth factor (VEGF) naïve or had not received anti-VEGF for ≥4 months. Patients received 3 monthly intravitreal injections of aflibercept 2.0 mg, bevacizumab 1.25 mg, or ranibizumab (0.5 mg for AMD/RVO, 0.3 mg for DME). The main outcome measures were serum PKs and plasma free-VEGF concentrations after the first and third injections. RESULTS: A total of 151 patients were included. In AMD/DME/RVO, systemic exposure to each drug was highest with bevacizumab, then aflibercept, and lowest with ranibizumab. Ranibizumab cleared from the bloodstream more quickly than bevacizumab or aflibercept. Aflibercept treatment resulted in the greatest reductions in plasma free-VEGF relative to baseline levels, whereas ranibizumab treatment resulted in the smallest decreases in plasma free-VEGF. CONCLUSION: The three anti-VEGF treatments examined in this analysis demonstrated notable differences in systemic PKs. Generally, the reduction in plasma free-VEGF levels correlated with elevated levels of circulating anti-VEGF agents, with the reduction in free-VEGF levels greatest with aflibercept and least with ranibizumab.

Vascular Endothelial Growth Factor Inhibitors for Diabetic Retinopathy.

The prevalence of diabetes is growing at epidemic rates in the USA. Diabetic retinopathy develops in a large proportion of patients and is a leading cause of blindness worldwide. Systemic management of diabetic retinopathy has included glycemic, hypertension, and lipid control. Local ophthalmic treatment in the form of focal/grid or panretinal laser photocoagulation has been shown to prevent vision loss in diabetic edema and proliferative diabetic retinopathy, respectively. The introduction of anti-vascular endothelial growth factor for diabetic macular edema and retinopathy has provided clinicians with improved clinical outcomes with potentially less damaging effects than laser.

Outer retina reflectivity changes on sd-oct after intravitreal ocriplasmin for vitreomacular traction and macular hole.

PURPOSE: To report initial experience with intravitreal ocriplasmin (IVO) and to describe outer retina reflectivity changes observed on spectral domain optical coherence tomography (SD-OCT) after IVO injection in patients with vitreomacular traction (VMT) with or without macular holes (MHs). METHODS: A consecutive retrospective review of patients with VMT and MH who were treated with IVO was performed. Patients underwent complete ophthalmic evaluation, including nonstandardized Snellen visual acuity testing, and SD-OCT at baseline and follow-up visits. RESULTS: A total of 23 patients who received IVO for VMT and/or MH were included for analysis. Patient age ranged from 53 years to 93 years with a mean of 74 years. The mean follow-up was 174 days (range: 20-291 days). Vitreomacular traction release at Day 30 after IVO was achieved in 11 of 23 patients (47.82%), at an average of 14.54 days (range: 1-30 days) after treatment. The mean visual acuity improved from 0.50 to 0.38. At presentation, eight patients had MH associated with VMT. Closure of the MH with ocriplasmin was achieved in two patients, and six patients underwent pars plana vitrectomy for MH repair. Ten of 23 patients (43.47%) presented with changes in the outer retina reflectivity on SD-OCT after IVO, 4 patients of this group experienced a decrease in visual acuity. In 7 of these 10 patients (70%), VMT release was documented on OCT by Day 30 postinjection compared with 4 of 13 patients (30.76%) without outer retina changes post-IVO. Normalization of the outer retina reflectivity was achieved in all cases. CONCLUSION: In this case series of VMT/MH patients treated with ocriplasmin, changes in the SD-OCT outer retina reflectivity were relatively common. Within weeks, the outer retinal reflectivity on SD-OCT improved, as did the visual acuity. Further studies to investigate the association between outer retina reflectivity changes with the use of IVO and long-term visual acuity outcomes are warranted.

Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD.

BACKGROUND: Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking. METHODS: Fifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections. RESULTS: Following the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) VEGF levels with ranibizumab were largely unchanged, with mean trough level of 14.4 pg/mL compared with baseline of 17 pg/mL. CONCLUSIONS: There are notable differences in systemic pharmacokinetics and pharmacodynamics among anti-VEGF treatments after intravitreal administration. All three agents rapidly moved into the bloodstream, but ranibizumab very quickly cleared, whereas bevacizumab and aflibercept demonstrated greater systemic exposure and produced a marked reduction in plasma free VEGF. TRIAL REGISTRATION NUMBER: NCT02118831.

Trans-tamponade optical coherence tomography: postoperative imaging in gas-filled eyes.

PURPOSE: To investigate the feasibility of trans-tamponade optical coherence tomography and evaluate factors contributing to image quality and acquisition success. METHODS: Retrospective case series of eyes receiving Postoperative Day 1 optical coherence tomography imaging after vitrectomy and gas tamponade. The quality of the scans was graded by three independent expert readers. Clinical and surgical variables were recorded and correlated with scan quality. RESULTS: Eighty eyes were included in the study. An image quality classification scheme was developed (0-4, 0 = no image and 4 = comparable quality to trans-fluid optical coherence tomography). In 51 scans (64%), visualization of the inner retina and retinal pigment epithelium was achieved (Grades 2-4) but with variable image quality of the retinal layers. Twenty-nine scans (36%) achieved visualization of all retinal layers (Grades 3-4). Only 9 scans (11%) were of comparable quality to fluid-filled eyes (Grade 4). Pseudophakia (P = 0.0001), shorter operative times (P = 0.007), and macular surgery (P = 0.002) correlated with scan quality. An optimum scan protocol was developed to facilitate maximum quality images. CONCLUSION: Successful trans-tamponade optical coherence tomography through gas on Postoperative Day 1 is possible but significant variability exists in scan quality.