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Patterns of Early & Delayed Visual Response to Ranibizumab for nAMD

Researchers examined patterns of visual and anatomical response to ranibizumab treatment, as part of a retrospective subanalysis of HARBOR (a Phase III, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (p.r.n.) in patients with subfoveal neovascular age-related macular degeneration).

A total of 1,097 individuals with nAMD were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (p.r.n.) with monthly monitoring. Of the 1,097 people, 1,057 were included in the analysis as early responders (best-corrected visual acuity obtained at baseline and month three), and 988 individuals were included in the analysis as delayed responders (BCVA obtained at baseline, month three and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015.

Subjects were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month three) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month three but did so at month 12). The main outcomes were change from baseline in BCVA and central foveal thickness (CFT).

In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 63 (24.0 percent) of 263 were early responders; 40 (16.3 percent) of 246 were delayed responders. In the 0.5-mg p.r.n. group, 65 (24.6 percent) of 264 were early responders; 31 (12.6 percent) of 247 were delayed responders. In the 2.0-mg monthly treatment group, 68 (25.7 percent) of 265 were early responders; 35 (14.1 percent) of 248 were delayed responders. In the 2.0-mg p.r.n. treatment group, 70 (26.4 percent) of 265 patients were early responders; 29 (11.7 percent) of 247 were late responders.

By month 12, early vs. delayed responders in the p.r.n. treatment groups received 7.5 vs. 7.4 ranibizumab injections, respectively (p=.84). More than 80 percent of early responders receiving p.r.n. treatment maintained 15-letter or greater gains at month 24. At baseline, early vs. delayed responders had worse BCVA (49.8 vs. 55.4 letters; p<.001) and greater CFT (374.9 vs. 339.0 µm; p=.02), although anatomical results were comparable by month three (CFT, 187.7 vs. 188.9 µm).

Improvement of 15 letters or more from baseline occurred in 266 (25.2 percent) of 1,057 individuals within three months of beginning ranibizumab treatment, whereas an additional 135 (13.7 percent) of 988 individuals achieved this gain by 12 months. The two cohorts had similar anatomical temporal response patterns. Researchers determined that p.r.n. treatment with monthly monitoring was effective in maintaining early vision gains and allowing delayed vision gains, suggesting that vision improvement can continue in some people after macular edema resolves and CFT decreases stabilize.

SOURCE: Stoller GL, Kokame GT, Dreyer RF, et al. Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2016 Mar 24. [Epub ahead of print].

Ranibizumab-treated AMD in ANCHOR, MARINA & HORIZON: Seven-year Outcomes

Investigators compared study and fellow eyes in subjects with age-related macular degeneration for seven-year outcomes arising from contrasting treatment histories and disease statuses, as part of a multicenter cohort study.

A total of 65 participants from the ranibizumab-treatment arms of the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR), Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the Treatment of Neovascular AMD (MARINA), and Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON) trials were recruited for an update evaluation from 14 study sites.

Seven-year visual outcomes and retinal imaging data were compared with the ANCHOR, MARINA and HORIZON databases. Under the ANCHOR and MARINA protocols, study eyes had received monthly ranibizumab injections for the initial two years, during which fellow eyes were prohibited from anti-VEGF treatments. Main outcome measures included: percentage of subjects with study eye vision better than fellow eye; vision change from baseline to year seven; and mean area of macular atrophy (MA). Fellow eyes with exudative AMD had received a mean 7.3 total injections of anti-VEGF agents in the mean 3.4 years off-study. For the 35 percent of subjects with exudative AMD in both eyes at baseline, within-subject comparisons at year seven showed better vision in the study eye in 82 percent, with better mean final vision in study eyes (54.7 vs. 27.3 letters in fellow eyes, p<0.001). Also in this subgroup, study eyes, which received two years of high-frequency ranibizumab, had less severe MA than fellow eyes at year seven in 88 percent of subjects (mean area ±standard deviation 2.8 ±2.2 mm² vs. 5.8 ±2.5 mm² in the fellow eyes, p=0.0013). Final fellow eye vision outcome was significantly correlated with MA severity (coefficient −6.95, p<0.001), and inter-eye vision difference corresponded to the degree of MA asymmetry.

Investigators found that exudative fellow eyes remained at risk for further vision decline in later years under management with low-frequency anti-VEGF therapy. In individuals with bilateral exudative AMD at baseline, final vision at year seven was significantly better in study eyes than in fellow eyes, and MA was less severe, investigators observed. In conclusion, they wrote, macular atrophy area correlated with final visual outcomes, determined inter-eye vision differences and was not attributable to high-frequency ranibizumab therapy.

SOURCE: Bhisitkul RB, Desai SJ, Boyer DS, et al. Fellow eye comparisons for 7-year outcomes in ranibizumab-treated AMD subjects from anchor, marina, and horizon (seven-up study). Ophthalmology. 2016; Mar 19. [Epub ahead of print].

Anti-VEGF Agents for nAMD

Scientists analyzed five-year results in treating neovascular age-related macular degeneration in individuals who initiated anti-vascular endothelial growth factor treatment before October 2009, via clinical practice data on visual/anatomical outcomes.

A total of 278 individuals met selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of individuals (71 percent) maintained stable VA throughout follow-up. At five years, mean central macular thickness remained substantially inferior to baseline (-96.6 µm), and 56 percent of people maintained dry retinas.

Scientists concluded that anti-VEGF therapy led to long-term visual stabilization in the majority of cases studied.

SOURCE: Pedrosa AC, Reis-Silva A, Pinheiro-Costa J, et al. Treatment of neovascular age-related macular degeneration with anti-VEGF agents: retrospective analysis of 5-year outcomes. Clin Ophthalmol. 2016;10:541-6.

mCNV Treated With Combined Ranibizumab & Dexamethasone

Researchers characterized the long-term outcomes of myopic choroidal neovascularization treated with combined ranibizumab and dexamethasone using multimodal imaging. A retrospective study of 20 eyes with mCNV treated with intravitreal ranibizumab and dexamethasone on an as-needed basis followed the cases for a mean period of 47 months (range 19 to 81 months).

The mean age was 55 ±16 years, with mean refractive error of -9.0 diopters. Subfoveal mCNV was seen in 11 eyes (52 percent); the other eyes were juxtafoveal. At the final visit, 13 individuals (65 percent) showed improvement, while four people (20 percent) had degradation in vision. The average number of ranibizumab and dexamethasone injections required was three ±1.7. Findings revealed a significant improvement in mean visual acuity; reduction of central retinal thickness; and expanding chorioretinal atrophy. The mean rate of increase in chorioretinal atrophy area was 0.05 ±0.09 mm²/month. Changes associated with active mCNV seen on optical coherence tomography included: disruption of the photoreceptor layer; fragmentation of the retinal pigment epithelium; and breaks in the Bruch’s membrane with a hyper-reflective lesion causing separation of the outer retinal layers.

Researchers reported that visual outcomes of mCNV treated with ranibizumab and dexamethasone on a treat-as-needed basis had favorable VA outcomes. They suggested that using multimodal imaging to monitor treatment response for chorioretinal atrophy should be used as an additional outcome measure to study the effect of combination treatment vs. monotherapy.

SOURCE: Tan ACS, Teo K, Guan OS, et al. Long-term outcomes of myopic choroidal neovascularisation treated with combined ranibizumab and dexamethasone characterised by multi-modal imaging. Graefe’s Arch Clin Exp Ophthalmol. 2016; Mar 12. [Epub ahead of print].

Intravitreal Injections of Ziv-Aflibercept for DME: A Pilot Study

Investigators evaluated the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of diabetic macular edema as part of a pilot study.

Seven consecutive individuals with DME were enrolled. A complete exam, including full-field electroretinography; visual acuity; central retinal thickness; and evaluation of systemic and ocular complications, was performed before and at 24 weeks after intravitreal injections of ziv-aflibercept. All subjects were submitted to six consecutive intravitreal injections of ziv-aflibercept with a four-week interval.

No significant differences were found in the amplitude or implicit time of any electroretinography component after intravitreal injections of ziv-aflibercept, and no systemic or ocular complication was observed. VA improvement was significant at 24 weeks (p<0.05). Central retinal thickness significantly decreased over 24 weeks.

Investigators concluded that intravitreal injections of ziv-aflibercept appeared to be a safe and effective treatment option for DME.

SOURCE: Andrade GC, Dias JR, Maia A, et al. Intravitreal injections of ziv-aflibercept for diabetic macular edema: a pilot study. Retina. 2016; Mar 16. [Epub ahead of print].

Review of Approved Pharmaceutical Agents for ME Secondary to RVO

According to researchers, three approved pharmaceutical agents exist to treat macular edema secondary to retinal vein occlusion: dexamethasone (a corticosteroid) implant, and ranibizumab and aflibercept (both antivascular endothelial growth factor agents). All agents show a superior ability to improve vision and reduce macular thickness in comparison with sham injections or macular grid laser treatment, researchers wrote, but prompt treatment with these agents may lead to a better outcome.

A review of randomized trials of injected aflibercept or ranibizumab revealed protocol variations, noted by researchers. They included “as-needed” injections until functional and anatomical changes were achieved, preceded by either one injection, or three to six monthly injections as loading doses. Ocular and systemic adverse effects of vascular endothelial growth factor antagonists for macular edema secondary to RVO were reportedly rarely severe. The antiedematous response to a single intravitreal dexamethasone implant was maximal one to three months post-injection, according to findings.

As a result of their review, researchers suggested that intraocular pressure elevation and cataract aggravation should be monitored after use of intravitreal dexamethasone implants. They noted that intravitreal dexamethasone implants and ranibizumab injections reduced not only macular edema, but also the risk of retinal ischemia and neovascularization in individuals with RVO.

SOURCE: Wang J-Kang. A review of randomized trials of approved pharmaceutical agents for macular edema secondary to retinal vein occlusion. Asia Pac J Ophthalmol. 2016;5(2):159-64.

Eradicating Helicobacter pylori in Acute CSCR Treatment

Scientists estimated the efficiency of Helicobacter pylori infection eradication in treatment of individuals with acute central serous chorioretinopathy.

Ninety-three people with acute CSCR participated in the study. They were divided into an experimental group (33 people positive for H. pylori who received eradication treatment) and two control groups that did not receive eradication treatment: 29 H. pylori-positive and 31 H. pylori-negative individuals. Research measurements included: best-corrected Snellen visual acuity, optical coherence tomography and fluorescein angiography. The follow-up period was two years.

Helicobacter pylori eradication decreased disease duration at three months (p=0.04); and resulted in recurrence frequency of 45.6 percent (p=0.03) and improvement of distant prognosis. After two years, VA increased from 0.91 ±0.07 to 0.99 ±0.02 (p=0.01); scotoma frequency decreased from 100 percent of eyes to 27.2 percent of eyes (p=0.001); and metamorphopsia frequency decreased from 57.6 percent of eyes to 39.4 percent of eyes (p=0.04).

Scientists concluded that Helicobacter pylori eradication assisted in treating individuals with acute central serous chorioretinopathy who were positive for H. pylori infections.

SOURCE: Zavoloka O, Bezditko P, Lahorzhevska I, et al. Clinical efficiency of Helicobacter pylori eradication in the treatment of patients with acute central serous chorioretinopathy. Graefe’s Arch Clin Exp Ophthalmol. 2016; Mar 16 [Epub ahead of print].

Visual Outcome & Prognostic Factors in Isolated Idiopathic Retinal Vasculitis

Scientists described the clinical course, visual outcome and prognosis of isolated, idiopathic retinal vasculitis.

Eighty subjects (150 eyes) were included. Demographic data; clinical data; complications at initial visit and during follow-up; fluorescein angiography; and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database from September 2005 to February 2015.

Seventy-five (93.7 percent) of individuals required treatment with immunomodulatory therapy. Of those people, 60 (75 percent) achieved durable remission. Factors that were independently significantly predictive of poor visual outcome were: lower initial visual acuity (OR: 3.78; 95 percent CI: 1.75-8.16; p=0.001); cystoid macular edema (OR: 5.54; 95 percent CI: 1.81-16.99; p=0.003); and macular ischemia (OR: 5.12; 95 percent CI: 1.12-23.04; p=0.036).

Scientists determined that the majority (67.25 percent) of individuals experienced a good visual outcome (most recent visit best-corrected visual acuity ≥20/40 and within one line or better from the baseline) with immunomodulatory therapy. CME; macular ischemia; and lower BCVA during the first consultation visit were found to be significant independent risk factors for poor visual outcome.

SOURCE: Maleki A, Cao JH, Silpa-Archa S, et al. Visual Outcome and Poor Prognostic Factors In Isolated Idiopathic Retinal Vasculitis. Retina. 2016; Mar 16. [Epub ahead of print].

Birdshot Chorioretinitis Lesions on ICG Angiography as a Disease Indicator

Researchers analyzed whether classical indocyanine green (IGC) angiography lesions in individuals with birdshot chorioretinitis could be used to monitor disease activity.

A retrospective case series was performed on 26 eyes in 26 consecutive individuals with birdshot chorioretinitis who had at least one IGC angiography performed during disease activity and another during disease quiescence. Using Adobe Photoshop, the mean number; area; and area per spot on IGC angiography were compared between disease activity and quiescence, using a paired ratio test.

During disease activity, the mean total lesion number was 75.27 spots, with 24,525 pixels and 364 pixels/spots. During disease quiescence, the mean total lesion number was 28.35 spots (p<0.01), with 7,411 pixels (p<0.01) and 279 pixels/spot (p=0.12).

A statistically significant decrease in the mean total area and number of lesions between the time of disease activity and quiescence (p<0.01) was observed. Researchers wrote that their results suggested that ICG angiography has a role, not only in diagnosis, but also in monitoring treatment effectiveness, since lesions could be reversible with treatment, and reappearance might indicate disease relapse.

SOURCE: Cao JH; Silpa-Archa S, Freitas-Neto CA., et al. Birdshot chorioretinitis lesions on indocyanine green angiography as an indicator of disease activity. Retina. 2016; Mar 14.

Small-gauge Valved Vs. Nonvalved Cannula PPV for Retinal Detachment Repair

To compare functional and anatomical outcomes and complication rates between valved vs. traditional nonvalved small-gauge cannula vitrectomy for retinal detachment repair, scientists conducted a retrospective case series of 163 eyes undergoing small-gauge valved vs. nonvalved vitrectomy with intraoperative perfluoro-n-octane for retinal detachment repair at a single academic institution.

A total of 104 eyes in the valved cannula group and 59 eyes in the nonvalved cannula group were included. The valved group had lower baseline, grade C-proliferative vitreoretinopathy (35 percent vs. 53 percent, p=0.031) and combined rhegmatogenous retinal detachment/tractional retinal detachment (3 percent vs. 12 percent, p=0.037), but both groups had otherwise comparable preoperative characteristics. Final postoperative best-corrected visual acuity was 1.01 LogMAR (Snellen 20/205) in valved and 1.27 (Snellen 20/372) in nonvalved cannula eyes (p=0.131). Single-surgery success was equivalent between the valved and nonvalved groups (88 percent vs. 86 percent; p=1.00). Final anatomical success was higher in the valved vs. nonvalved group (98 percent vs. 90 percent; p=0.027). Complication rates were not statistically different, including: postoperative day one intraocular pressure; postoperative day one anterior chamber fibrin; retained subretinal/intraocular perfluoro-n-octane; and epiretinal membrane peeling.

Scientists noted that valved cannulas, with improved fluidics, are an important addition to PPV, offering similar functional/anatomical success and no increase in complication rates compared with traditional nonvalved cannulas.

SOURCE: Oellers P, Stinnett S, Mruthyunjaya PM, et al. Small-gauge valved versus nonvalved cannula pars plana vitrectomy for retinal detachment repair. Retina. 2016;36(4):744-9.

Surgical Techniques for Managing PARD

Researchers compared the visual and anatomical outcomes of four surgical techniques to manage pseudophakic and aphakic retinal detachment (PARD) in a multicenter randomized clinical trial.

A total of 211 eyes of 211 people with PARD and proliferative vitreoretinopathy grade B or less were randomly assigned to one of four treatment groups: scleral buckling (SB): 50 eyes; vitrectomy without band: 51 eyes; vitrectomy with encircling band (EB): 58 eyes; and triamcinolone acetonide (TA)-assisted vitrectomy: 52 eyes. Individuals were followed for 12 months after the surgery. The best-corrected visual acuity and retinal reattachment rate at each follow-up time point were primary outcome measures. PVR, macular pucker, and cystoid macular edema were secondary outcomes.

Visual improvement was achieved in all treatment groups relative to the baseline at all time points (p< 0.001). No statistically significant differences were detected among the groups with regard to BCVA changes. However, significant differences were found in the slope of visual improvement curve: The SB group had a more rapid visual improvement compared to the vitrectomy with buckle group at month 12 (p= 0.032). The retinal reattachment rates at month 12 were: 75 percent in SB; 64.7 percent in vitrectomy without buckle; 68.5 percent in vitrectomy with EB; and 66.7 percent in TA-assisted vitrectomy groups (p>0.99). No statistically significant differences in adverse events were found among the groups.

Researchers determined that SB; TA-assisted vitrectomy; and vitrectomy with and without buckle had comparable outcomes in managing PARD.

SOURCE: Moradian S, Ahmadieh H, Faghihi H, et al. Comparison of four surgical techniques for management of pseudophakic and aphakic retinal detachment: a multicenter clinical trial. Graefe’s Arch Clin Exp Ophthalmol. 2016; Mar 12. [Epub ahead of print].

Preoperative OCT Parameters & Visual Outcome Post-vitrectomy

Investigators examined the effect of preoperative optical coherence tomography features on postoperative visual acuity after epiretinal membrane surgery.

The retrospective, consecutive case series involved individuals with symptomatic idiopathic ERMs who underwent vitrectomy and membrane peel between 2008 and 2013. The main outcomes were postoperative letter score and change in letter score. The association between visual acuity and OCT features was estimated using linear regression, correcting for important baseline covariates. OCT features included: central foveal thickness; maximum retinal thickness; retinal cross-sectional area; central photoreceptor thickness; central epiretinal membrane; intraretinal cyst presence and location; retinal contraction; foveal ellipsoid zone and external limiting membrane integrity; and pseudoholes.

A total of 79 subjects were included in the study. Mean VA was 65.0 letters preoperatively and 68.9 letters postoperatively, with average follow-up of 92 days. Better postoperative VA was associated with presence of preoperative retinal contraction (6.4 letters p=0.027) and lower preoperative maximum retinal thickness values (0.34 letters per 10 μm reduction, p=0.003). Change in VA was associated with preoperative foveal ellipsoid zone attenuation (6.6 letters more improvement when present, p=0.013). Preoperative pseudoholes were associated with a smaller change in VA (7.4 letters less improvement, p=0.034). No other OCT features were significant, including intraretinal cyst presence and location. Better preoperative VA was associated with better postoperative acuity, but less change in VA.

Investigators found that preoperative maximum retinal thickness and retinal contraction were predictive of better postoperative VA, while individuals with a preoperative attenuated foveal ellipsoid zone were most likely to improve. Those with preoperative pseudoholes reportedly had slightly worse VA postoperatively. Although better preoperative vision was associated with better postoperative vision, it was also associated with less VA change. Investigators said the findings emphasized the importance of clinicians carefully considering their desired surgical goals before advising surgery for ERM.

SOURCE: Sheales MP, Kingston ZS, Essex RW. Associations between preoperative OCT parameters and visual outcome 3 months postoperatively in patients undergoing vitrectomy for idiopathic epiretinal membrane. Graefe’s Arch Clin Exp Ophthalmol. 2016;Mar 30. [Epub ahead of print].