Volume 12, Number 7
July 2016


WELCOME to Review of Ophthalmology's Retina Online e-newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

Ophthotech Completes Patient Recruitment in Phase III Trial
Ophthotech Corp. completed patient recruitment in its Phase III trial of Fovista (pegpleranib) anti-PDGF therapy in combination with Eylea (aflibercept) or Avastin (bevacizumab) for the treatment of wet age-related macular degeneration...

Eleven Biotherapeutics IND for EBI-031 Now in Effect
Eleven Biotherapeutics announced that the company's Investigational New Drug application for EBI-031, a humanized monoclonal antibody that potently binds interleukin-6 and inhibits all known forms of IL-6 cytokine signaling, for treatment of ocular diseases, is effective...

And More...

Differential Response to Anti-VEGF Regimens in AMD With Early Persistent Retinal Fluid

Researchers compared the effect of intravitreal aflibercept or ranibizumab drug type and frequency on visual acuity outcomes in eyes with neovascular age-related macular degeneration and early persistent retinal fluid after three initial monthly injections, as part of a post hoc analysis of eyes enrolled in VIEW 1 and VIEW 2, two similarly designed, randomized, Phase III trials sponsored by Regeneron and Bayer, collaborators in the development of aflibercept (Eylea). Several of the study’s authors are researchers at Regeneron.

A total of 1,815 eyes with NVAMD from VIEW 1 and VIEW 2 were included. Analyses included individuals with known fluid status at baseline, and weeks four, eight and 12 in three treatment groups: ranibizumab 0.5 mg every four weeks (Rq4) (n=595); intravitreal aflibercept injection (IAI) 2 mg every four weeks (2q4) (n=613); and IAI 2 mg every eight weeks (2q8) after three monthly injections (n=607).

Main outcome measures included mean BCVA change from baseline over weeks 16 to 52, and the proportion of eyes that gained ≥15 letters or lost ≥5 letters in eyes with and without persistent fluid (cystic intraretinal or subretinal fluid at all four initial visits). Visual outcomes also were assessed in eyes with persistent fluid, by fluid type (i.e., intraretinal and subretinal).

The proportion of eyes with persistent fluid was: 29.4 percent in the Rq4 group; 18.8 percent in the 2q4 group; and 20.3 percent in the 2q8 group. Mean BCVA gain from baseline to week 52 was greater in 2q4 compared with Rq4 (p<0.01) and 2q8 (p<0.05). Mean BCVA gain was similar in Rq4 and 2q8 (p=0.294). At week 52, similar proportions of eyes gained ≥15 letters (31.5 percent to 35.2 percent), while fewer eyes lost ≥5 letters in 2q4 compared with Rq4 and 2q8 (6.5 percent vs. 16.6 percent and 16.2 percent). The pattern of visual outcomes was similar regardless of fluid type. In eyes without persistent fluid, BCVA changes were similar across treatment groups.

Researchers concluded that, in individuals with early persistent fluid, 2q4 may provide additional clinical benefits over 2q8 or Rq4.

SOURCE: Jaffe GJ, Kaiser PK, Thompson D, et al. Differential response to Anti-VEGF regimens in age-related macular degeneration patients with early persistent retinal fluid. Ophthalmology 2016; June 28. [Epub ahead of print].

Reticular Pseudodrusen Not Predictive for Intravitreal Ranibizumab Response in nAMD

Investigators analyzed reticular pseudodrusen as a potential baseline factor predictive of a poor one-year response to intravitreal ranibizumab in eyes with neovascular age-related macular degeneration.

The retrospective, monocentric case series include 98 consecutive treatment-naive nAMD cases. Two graders assessed presence of RPD based on color, blue-light, fundus autofluorescence pictures; and spectral-domain optical coherence tomography. Researchers looked at the correlation between the presence of RPD and visual change. Other baseline characteristics studied in a monovariate and multivariate analysis included: age; gender; affected side; loading dose; type of neovascularization; presence of retinal pigment epithelial detachment >250 µm; subretinal or intraretinal fluid; blood over >50 percent of the lesion; and subfoveal choroidal thickness.

The presence of RPD was not associated with a visual change (p=0.96), but with a thin subfoveal choroidal thickness at baseline (p<0.0001). The monovariate analysis showed that presence of blood at baseline was associated with visual gain (p=0.007).

Investigators concluded that presence of RPD at baseline was not associated with a poor one-year response to ranibizumab in eyes with nAMD. They suggested that studies with a longer follow-up period may be needed to assess the impact of RPD on the visual prognosis of eyes with nAMD.

SOURCE: Nghiem-Buffet S, Giocanti-Auregan A, Jung C, et al. Reticular pseudodrusen are not a predictive factor for the 1-year response to intravitreal ranibizumab in neovascular age-related macular degeneration. Retina 2016; July 1. [Epub ahead of print].


Ranibizumab vs. Bevacizumab for nAMD Degeneration With Incomplete Posterior Vitreous Detachment

Researchers aimed to compare the effects of ranibizumab to those of bevacizumab during the treatment of neovascular age-related macular degeneration with an incomplete posterior vitreous detachment.

A retrospective chart review was performed on treatment-naive nAMD subjects with an incomplete posterior vitreous detachment treated with either ranibizumab or bevacizumab over a 12-month period.

One-hundred-thirty subjects were analyzed, with 49 determined to have vitreous attachment to the fovea. Subjects with vitreous attachment to the fovea required a significantly greater number of injections during the study interval compared with those without (10.2 ±0.75 vs. 7.8 ±0.62; p<0.0001). In subjects with vitreous attachment to the fovea, the ranibizumab cohort had a greater improvement in visual acuity (0.18 ±0.1 vs. 0.04 ±0.11 logMAR; p=0.0176) and a greater reduction in macular thickness (93.4 ±32.2 μm vs. 30.3 ±28.3 μm; p=0.0064) compared with the bevacizumab cohort.

Researchers concluded that individuals with nAMD and vitreous attachment to the fovea may have better visual and anatomic outcomes when treated with ranibizumab compared with bevacizumab.

SOURCE: Rush RB, Rush SW. Ranibizumab versus bevacizumab for neovascular age-related macular degeneration with an incomplete posterior vitreous detachment. Asia Pac J Ophthalmol 2016;5:3:171-5.

Outer Retinal Tubulations in Eyes Switched from Intravitreal Ranibizumab to Aflibercept for Exudative AMD Treatment

Investigators evaluated changes in outer retinal tubulations as seen on spectral-domain optical coherence tomography in eyes with neovascular age-related macular degeneration where treatment was switched from intravitreal ranibizumab to intravitreal aflibercept.

Investigators conducted the prospective study of eyes at a single center (Pitié Salpetriere Hospital, Paris VI University) from January 2015 to July 2015. Researchers used SD-OCT to evaluate presence of ORTs before and after treatment was switched. Additional assessments included best-corrected visual acuity, fluorescein angiography and indocyanine green angiography. In addition, investigators noted changes in pigment epithelium detachments, and presence of intraretinal cysts and subretinal fluid.

Twenty-four eyes of 24 consecutive cases (15 females/nine males, mean age: 70 years) diagnosed with neovascular AMD previously treated with more than six intravitreal ranibizumab injections and switched to aflibercept were included. After receiving aflibercept, individuals were followed for a mean of 6.1 months. Prior to the treatment switch, 97 percent of eyes showed ORTs; after the treatment switch to aflibercept at the end of the study period, 75 percent had ORTs (p=0.219). BCVA changes (LogMAR) were not statistically significant (1.16 ±0.44 to 1.18 ±1.06, p=0.12); however, investigators noted a significant reduction in central macular thickness (406 ±112 μm to 263 ±68 μm, p=0.001); PED (70.8 percent to 41.7 percent, p=0.016); presence of intraretinal cysts (83.3 percent to 33.3 percent, p=0.002); and SRF (91.7 percent to 25 percent, p=0.001).

Investigators found that ORTs remained in 75 percent of eyes, and noted significant reductions in CMT, PED and SRF, along with presence of intraretinal cysts, after cases were switched from ranibizumab treatment to aflibercept.

SOURCE: Massamba N, Dirani A, Butel N, et al. Evaluation of outer retinal tubulations in eyes switched from intravitreal ranibizumab to aflibercept for treatment of exudative age-related macular degeneration. Graefe’s Arch Clin Exp Ophthalmol 2016; July 11. [Epub ahead of print].

Recalcitrant Cystoid Macular Edema After PPV

Scientists evaluated treatment outcomes for chronic cystoid macular edema after pars plana vitrectomy, as part of a retrospective review focused on eyes that developed chronic CME after PPV treated with intravitreal triamcinolone acetonide with or without the addition of anti-vascular endothelial growth factor.

Thirty-nine eyes of 37 individuals were included, with a median duration between PPV and onset of CME of five months (interquartile range, three to 12). In most eyes (66.7 percent), the main indication for surgery was for vitreomacular interface disorders, such as epiretinal membrane, vitreomacular traction and macular hole. With intravitreal TCA, a significant decrease in central foveal thickness could be found, compared with baseline at three months (p=0.0171), six months (p=0.0401) and 12 months (p=0.0024). Researchers noted a significant gain in vision at one month compared with baseline (p=0.0169), which wasn’t sustained at three months (p=0.4862), six months (p=0.9098) and 12 months (p=0.4312). The addition of bevacizumab to TCA didn’t provide additional benefit for central foveal thickness and visual acuity. Thirty-two eyes (82.1 percent) were started on prophylactic anti-glaucoma drops two weeks after a TCA injection, and no eyes needed lasers or surgery to control intraocular pressure.

The investigators wrote that chronic CME after PPV is recurrent and difficult to treat, and though intravitreal TCA was effective in reducing CME, only short-term VA improvements were found, even with continued reduction of central foveal thickness. IOP didn’t significantly rise with use of prophylactic antiglaucoma drops, even with repeated injections, the researchers also determined.

SOURCE: Alam MR, Arcinue CA, Mendoza Nadia, et al. Recalcitrant cystoid macular edema after pars plana vitrectomy. Retina 2016; June 15. [Epub ahead of print].

RVO Treated With Low-frequency Intravitreal Ranibizumab

Investigators assessed the clinical efficacy of low-frequency intravitreal ranibizumab to treat macular edema due to retinal vein occlusion, as part of a retrospective examination of cases that received intravitreal ranibizumab for untreated RVO over a period of 12 months.

Instead of the conventional three monthly injections, injections were given once during the introductory period. If the recurrence of macular edema was diagnosed during the monthly visit, additional injections were given as needed. Twenty-one eyes of 21 individuals with branch RVO, and 10 eyes of 10 subjects with central RVO were included. Parameters examined included the number of injections over the 12-month period, improvements in best-corrected visual acuity, and the central macular thickness. For BRVO, preinjection parameters that had an effect on the prognosis of BCVA after the 12-month period were also examined.

The total mean number of injections over the 12-month period was 3.4 for CRVO and 2.1 for BRVO. For CRVO, the BCVA in LogMAR changed from a pre-injection value of 0.80 µm to 0.55 µm at 12 months. For BRVO, the change was from 0.51 µm to 0.30 µm. For all diseases, BCVA improved after 12 months compared with the pre-injection values (p<0.05). CMT showed improvement, and CRVO changed from 765 µm at pre-injection to 253.5 µm 12 months later. BRVO changed from 524.1 µm to 250.1 µm, and pre-injection BCVA was associated with a prognosis of visual acuity after 12 months of the initial injection (p=0.0485).

Investigators found improvements in both visual acuity and CMT in RVO after 12 months, despite the low number of injections during the introductory period, indicating low-frequency intravitreal ranibizumab was an effective treatment.

Source: Sakanishi Y, Lee A, Usui-Ouchi A, et al. Twelve-month outcomes in patients with retinal vein occlusion treated with low-frequency intravitreal ranibizumab. Clin Ophthalmol 2016;10:1161-5.

Reduction of Intravitreal Bevacizumab Administrations With Sub-Tenon’s Injection of Triamcinolone Acetonide in Diffuse DME

To evaluate the effectiveness of posterior sub-Tenon’s injections of triamcinolone acetonide during treatment with intravitreal injections of bevacizumab in eyes with diffuse diabetic macular edema (DDME), scientists studied 40 eyes of 20 individuals with bilateral DDME with foveal thickness greater than 400 μm.

Initially, both eyes of each subject received 1.25 mg/0.05 ml of IVB. One eye then received 20 mg/0.5 ml of STTA at the onset; and at 16, 32 and 48 weeks. For the control, the other eye was not treated with STTA. Individuals were treated with additional IVB when DDME recurred during the study to maintain the FT at <350 μm. Researchers measured the FT; logMAR visual acuity; and intraocular pressure monthly for 56 weeks. They also tallied the total number of IVB injections during the one-year follow-up.

STTA-treated eyes had significantly more regression of FT and improvement of VA at several time points during the study than did the controls. The mean (SD) required number of IVB injections in the STTA-treated eyes during the study was 5 ±1.75, which was significantly less than the 7.95 ±1.57 in the control eyes.

Scientists determined that adjunctive STTA therapy to IVB for the treatment of DDME not only improved the morphological and functional regressions but also reduced the frequency of IVB treatments.

SOURCE: Shimura M, Yasuda K, Minezaki T, et al. Reduction in the frequency of intravitreal bevacizumab administrations achieved by posterior subtenon injection of triamcinolone acetonide in patients with diffuse diabetic macular edema. Jpn J Ophthalmol 2016; June 15. [Epub ahead of print].


Ophthotech Completes Patient Recruitment in Phase III Trial

Ophthotech Corp. completed patient recruitment in its Phase III trial of Fovista (pegpleranib) anti-PDGF therapy in combination with Eylea (aflibercept) or Avastin (bevacizumab) for the treatment of wet age-related macular degeneration. Ophthotech also announced that it achieved a $30 million enrollment milestone from Novartis Pharma AG as part of the ex-U.S. licensing and commercialization agreement between the two companies focused on the treatment of wet AMD. The Fovista Phase III program consists of three clinical trials to evaluate the safety and efficacy of Fovista in combination with multiple anti-VEGF agents for the treatment of wet AMD. The company completed enrollment in its two other Phase III trials of Fovista in combination with Lucentis (ranibizumab) last year and expects to announce initial, topline data from these two studies in the fourth quarter of this year. Read more.

Source: Ophthotech Corp., June 2016

Eleven Biotherapeutics IND for EBI-031 Now in Effect

Eleven Biotherapeutics announced that the company's Investigational New Drug application for EBI-031, a humanized monoclonal antibody that potently binds interleukin-6 and inhibits all known forms of IL-6 cytokine signaling, for treatment of ocular diseases, is effective. As a result, Eleven is entitled to receive a $22.5 million payment from F. Hoffmann-La Roche Ltd. and Hoffmann-La Roche Inc. (Roche) pursuant to the terms of its license agreement with Roche. On June 13, 2016, Eleven announced that it had entered into an exclusive license agreement with Roche for the further development and commercialization of EBI-031 and all other IL-6 antagonist antibody technology owned by Eleven. Abbie Celniker, PhD, president and CEO of Eleven Biotherapeutics, said the company looks forward to Roche advancing EBI-031 into the clinical realm to explore its potential use for ocular diseases, such as diabetic macular edema. Read more.

Source: Eleven Biotherapeutics, July 2016

AiVita Awarded CIRM Grant for Development of 3D-Transplantable 'Retinas'

AiVita Biomedical announced that the California Institute for Regenerative Medicine approved the company to collaborate on an early translational research awards grant for development of stem cell-derived 3D-transplantable retinas to treat vision loss. The project is being conducted in collaboration with Assistant Professor Magdalene Seiler, PhD, at the Sue & Bill Gross Stem Cell Research Center at the University of California-Irvine. AiVita's role is to manufacture the 3D-retinal organoids and render the process clinically and commercially compliant using its GMP manufacturing, quality and regulatory systems. UCI's role is to test the product for safety and efficacy in relevant models of retinal degeneration. Read more.

Source: AiVita Biomedical, July 2016

RetroSense Named to MIT Technology Review’s 50 Smartest Companies

RetroSense Therapeutics announced that MIT Technology Review selected RetroSense as one of the 50 Smartest Companies in 2016. Editors at the publication conduct an annual search for the smartest companies with an innovative technology and a practical, yet ambitious, business model. RetroSense is developing a novel gene therapy application of optogenetics to treat retinitis pigmentosa. The company’s Investigational New Drug application for RST-001 received clearance from the U.S. Food and Drug Administration in 2015, and the clinical trial was initiated in early 2016. Read more.

Source: RetroSense Therapeutics, June 2016

Topcon Selected for IBM Global Medical Imaging Collaborative

IBM, which is forming the Watson Health medical imaging collaborative, named Topcon Corp., to be among the collaborative’s 16 partners. The group includes academic medical centers, health systems, ambulatory radiology providers and imaging technology companies. As part of this global effort, members will engage IBM's "augmented intelligence" platform, known as Watson, to extract insight from structured and unstructured data sources including medical imaging data, electronic health records, radiology and pathology reports, laboratory results, doctors' progress notes, medical journals, clinical care guidelines and published outcomes studies. Watson, a cognitive computing system, understands natural language, and can reason and learn over time. Topcon will leverage its family of imaging devices to facilitate and optimize the Watson training process, and accelerate development of products and services that improve the diagnosis and treatment of eye diseases. Read more.

Source: Topcon, June 2016

Bausch + Lomb & Nicox Publish Phase III Study Results

Bausch + Lomb and Nicox announced that the results of a Phase III study for latanoprostene bunod (LBN) ophthalmic solution 0.024% were published in the American Journal of Ophthalmology. The results of the LUNAR study demonstrated that LBN 0.024% administered once daily in the evening was not only non-inferior to timolol maleate 0.5% dosed twice daily in subjects with OAG or OHT over three months of treatment, but also provided significantly greater IOP reduction (p≤0.025) at all but the earliest time point evaluated. Read more.

Source: Bausch & Lomb, July 2016

European Research Offers Potentially Improved Vision for Healthy Eyes

Irish-based research published in Investigative Ophthalmology & Visual Science holds the prospect of sharper vision for individuals who already have good eyesight. While most research in this area has focused on corrective action for those who’ve already suffered vision loss as a result of eye disease, the new study concentrated on those with healthy eyesight, and still found marked improvements in vision among those receiving specific dietary supplements over a year. The CREST (Central Retinal Enrichment Supplementation Trials) study was conducted by the Macular Pigment Research Group at Nutrition Research Centre Ireland, part of the School of Health Sciences at Waterford Institute of Technology. Read more.

Source: Waterford Institute of Technology, June 2016

Eyenuk Announces CE Mark and Commercial Launch of EyeArt 2.0

Eyenuk announced receipt of the CE Mark and launch of the second generation of its fully automated diabetic retinopathy screening software. The company plans to roll out EyeArt 2.0 to select eye-care centers in Europe over the next few months. The commercial launch is supported by a new study of the technology demonstrating 98.3-percent sensitivity in identifying potentially treatable patients with severe nonproliferative or proliferative DR, and/or the presence of surrogate markers for clinically significant macular edema. Read more.

Source: Eyenuk, June 2016

Apple & Donate Life America Enable Eye Organ Donor Registration on iPhone

Apple and Donate Life America announced that iPhone users will be able to sign up to be an organ, eye and tissue donor from the Apple Health app with the release of iOS 10. Through a simple sign-up process, iPhone users can learn more and take action. All registrations submitted from iPhone are sent directly to the National Donate Life Registry managed by Donate Life America. Read more.

Source: Apple, July 2016

New Global AMD Therapeutics Report Released

Research and Markets announced the addition of the “Age Related Macular Degeneration - Pipeline Review, H1 2016” report to its offerings. The report provides comprehensive information on the therapeutic development for AMD, complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action, route of administration and molecule type, along with the latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for AMD and special features on late-stage and discontinued projects. Read more.

Source: Research and Markets, May 2016

Retina Implant AG Announces Change in Leadership

Following 12 years of successful development at Retina Implant AG, Dr. Walter-G. Wrobel, CEO of the company, announced his resignation by mutual consent, to take effect September 30, 2016. Dr. Wrobel's departure, along with recent CE-approval of the new Retina Implant Alpha AMS, indicates a new era for the company that will be heavily influenced by navigating the challenges of distribution. Reinhard Rubow, who has been on the board for 13 years, will step up to lead Retina Implant AG as sole executive director, starting October 1, 2016. Read more.

Source: Retina Implant AG, July 2016


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