Volume 14, Number 29
Monday, July 21, 2014


In this issue: (click heading to view article)
######### Documented VF Improvements in a Glaucoma Treatment Study

######### Comparing Moderate Amblyopia Treatments: Atropine vs. Patching
######### Intravitreal Aflibercept for the Treatment of Macular Edema Due to CRVO
######### Aflibercept Treatment for Patients With Exudative AMD Who Were Incomplete Responders to Ranibizumab Injections
######### Briefly


Documented VF Improvements in a Glaucoma Treatment Study

The researchers in this prospective, comparative case series aimed to evaluate critical visual field improvement in participants in the Collaborative Initial Glaucoma Treatment Study.

The case series is based on a randomized clinical trial comparing trabeculectomy and topical medications in treating open-angle glaucoma. The researchers identified 607 subjects with newly diagnosed OAG for study. They obtained baseline and follow-up VF tests and analyzed mean deviation change from baseline over follow-up. Furthermore, they defined clinically substantial change (loss or improvement) as change from baseline of ≥3 decibels in MD. They also inspected baseline factors to determine their association with VF improvement in repeated measures regression models.

According to the study researchers, the percentage of participants showing substantial VF improvement over time was similar to that showing VF loss through five years after initial treatment, after which VF loss became more frequent. They also noted that measures of better intraocular pressure control during treatment were significantly predictive of VF improvement, including a lower mean IOP, a lower minimum IOP and lower sustained levels of IOP over follow-up. Other predictive factors included female sex (odds ratio=1.73), visits one year prior to cataract extraction (OR=0.11), and an interaction between treatment and baseline MD wherein surgically treated subjects with worse baseline VF loss were more likely to show VF improvement.

To conclude, in the CIGTS, substantial VF loss and improvement were comparable through five years of follow-up, after which VF loss became more frequent. Predictive factors for VF improvement included several indicators of better IOP control, which supports the postulate that VF improvement was real.

SOURCE: Musch DC, Gillespie BW, Palmberg PF, et al. Visual field improvement in the Collaborative Initial Glaucoma Treatment Study. Am J Ophthalmol. 2014;158(1):96–104.

Comparing Moderate Amblyopia Treatments: Atropine vs. Patching

While initial treatment for amblyopia of the fellow eye with patching and atropine sulfate eye drops improves visual acuity, long-term data on the durability of treatment benefit are needed.

The authors of the following multicenter clinical trial sought to report visual acuity at 15 years of age among patients who were younger than seven years when enrolled in a treatment trial for moderate amblyopia.

They randomly assigned 419 children with amblyopia (visual acuity, 20/40 to 20/100) to patching (minimum of six hours per day) or atropine sulfate eye drops, 1% (one drop daily) for six months. Treatment after six months was at the discretion of the investigator. Two years after enrollment, an unselected subgroup of 188 children were enrolled into long-term follow-up. Intervention consisted of initial treatment with patching or atropine with subsequent treatment at investigator discretion. Visual acuity at 15 years of age with the electronic Early Treatment Diabetic Retinopathy Study test in amblyopic and fellow eyes was the main outcome measure.

Mean visual acuity in the amblyopic eye measured in 147 participants at 15 years of age was 0.14 logMAR (approximately 20/25). The study authors noted that 59.9% of amblyopic eyes had visual acuity of 20/25 or better and 33.3%, 20/20 or better. They also reported that mean interocular acuity difference (IOD) at 15 years of age was 0.21 logMAR (2.1 lines); 48.3% had an IOD of two or more lines and 71.4%, one or more lines. Treatment (other than spectacles) was prescribed for nine participants (6.1%) aged 10 to 15 years. Mean IOD was similar at examinations at 10 and 15 years of age (2.0 and 2.1 logMAR lines, respectively; p=0.39). Better visual acuity at the 15-year examination was achieved in those who were younger than 5 years at the time of entry into the randomized clinical trial (mean logMAR, 0.09) compared with those aged 5 to 6 years (mean logMAR, 0.18; p<0.001). When the authors compared subgroups based on original treatment with atropine or patching, no significant differences were observed in visual acuity of amblyopic and fellow eyes at 15 years of age (p=0.44 and p=0.43, respectively).

They found that at 15 years of age, most children treated for moderate amblyopia when younger than 7 years have good visual acuity, although mild residual amblyopia is common. The outcome is similar regardless of initial treatment with atropine or patching. The results indicate that improvement occurring with amblyopia treatment is maintained until at least 15 years of age.

SOURCE: Repka MX, Kraker RT, Holmes JM, et al; for the Pediatric Eye Disease Investigator Group. Atropine vs. patching for treatment of moderate amblyopia. 2014;132(7):799–805.

Intravitreal Aflibercept for the Treatment of Macular Edema Due to CRVO

To evaluate the efficacy and safety of intravitreal aflibercept injection for the treatment of macular edema secondary to central retinal vein occlusion, this randomized, double-masked, Phase III trial included 188 patients with macular edema secondary to CRVO.

Patients received IAI 2 mg (IAI 2Q4) (n=114) or sham injections (n=74) every four weeks up to week 24. During weeks 24 to 52, patients from both arms were evaluated monthly and received IAI as needed, or pro re nata (IAI 2Q4 + PRN and sham + IAI PRN). During weeks 52 to 100, patients were evaluated at least quarterly and received IAI PRN. The primary efficacy endpoint was the proportion of patients who gained ≥15 letters in best-corrected visual acuity from baseline to week 24. This study reports week 100 results.

The proportion of patients gaining ≥15 letters was 56.1% vs. 12.3% (p<0.001) at week 24, 55.3% vs. 30.1% (p<0.001) at week 52, and 49.1% vs. 23.3% (p<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean change from baseline BCVA was also significantly higher in the IAI 2Q4 + PRN group compared with the sham + IAI PRN group at week 24 (+17.3 vs. –4.0 letters; p<0.001), week 52 (+16.2 vs. +3.8 letters; p<0.001), and week 100 (+13.0 vs. +1.5 letters; p<0.0001). The mean reduction from baseline in central retinal thickness was 457.2 vs. 144.8 µm (p<0.001) at week 24, 413.0 vs. 381.8 µm at week 52 (p=0.546), and 390.0 vs. 343.3 µm at week 100 (p=0.366) in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean number (standard deviation) of PRN injections in the IAI 2Q4 + PRN and sham + IAI PRN groups was 2.7 ± 1.7 vs. 3.9 ± 2.0 during weeks 24 to 52 and 3.3 ± 2.1 vs. 2.9 ± 2.0 during weeks 52 to 100, respectively. The most frequent ocular serious adverse event from baseline to week 100 was vitreous hemorrhage (0.9% vs. 6.8% in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively).

It was determined that the visual and anatomic improvements after fixed dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52 were diminished after continued PRN dosing, with a reduced monitoring frequency from weeks 52 to 100.

SOURCE: Heier JS, Clark WL, Boyer DS, et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion. Ophthalmology. 2014;121(7):1414–1420.

Aflibercept Treatment for Patients With Exudative AMD Who Were Incomplete Responders to Ranibizumab Injections

Investigators conducted the following prospective, open-label, single-arm clinical trial to determine the efficacy of 2.0 mg aflibercept in the management of patients with recalcitrant exudative age-related macular degeneration.

They saw patients monthly and administered mandatory 2.0 mg aflibercept at baseline and at months one, two and four. They also performed pro re nata retreatment at months three and five upon evidence of disease on spectral domain-optical coherence tomography. End point at month six was mean change in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity and central subfield thickness, mean number of aflibercept injections, percentage of p.r.n. injections required, patients with no fluid on SD-OCT and patients losing >15 letters.

At baseline, the investigators found that 46 patients with a mean of 42 prior anti-vascular endothelial growth factor-A intravitreal treatments had a mean of 74.2 letters (Snellen equivalent 20/32) and mean CST of 347 µm. They also noted that ETDRS letters remained stable throughout the trial; at month six, mean BCVA change was +0.2 letters (range –10 to +13, p=0.71). Anatomically, mean CST improved significantly from baseline at each study visit including –23.6 µm at month one and –27.3 µm at month six (p=0.018). Seventy-one of 90 (79%) possible p.r.n. injections were required and a mean of 5.6 aflibercept injections out of the maximum six were administered. Moreover, 10 of 45 (22%) patients had no retinal fluid on SD-OCT at month six and no patient lost >15 letters.

The study investigators concluded that aflibercept 2.0 mg treatment maintained mean visual acuity improvements previously achieved with high-dose 2.0-mg ranibizumab injections in recalcitrant wet AMD patients. Aflibercept 2.0 mg treatment led to significant anatomic improvement and was required monthly in most patients.

SOURCE: Wykoff CC, Brown DM, Maldonado ME, Croft DE. Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial). Br J Ophthalmol. 2014;98(7):951–955.

  • AERIE INITIATES PHASE III REGISTRATION TRIALS OF GLAUCOMA DRUG. Dosing of the first patients enrolled in Aerie Pharmaceuticals Inc.'s Phase III registration clinical trials of Rhopressa commenced on July 11th. Rhopressa is a novel, once-daily, triple-action eye drop being tested for its ability to lower intraocular pressure in patients with glaucoma or ocular hypertension. Aerie anticipates total enrollment of roughly 1,300 patients in three Phase III registration trials of Rhopressa that will measure efficacy over three months and safety over 12 months. The primary efficacy endpoint of the trials will be to demonstrate noninferiority of IOP lowering for Rhopressa compared to timolol. There will be two trials conducted in the United States, named “Rocket 1” and “Rocket 2,” and one safety-only study in Canada, named “Rocket 3.” Pending success of the studies and regulatory approval, Aerie expects Rhopressa to compete against PGA products as an initial therapy for patients with IOPs of 26 mmHg or below at the time of diagnosis. Pending successful advancement of the Phase III registration studies, three-month efficacy results are expected to be released in mid-2015. If the trials are successful, Aerie expects to submit a New Drug Application filing by mid-2016. Want to know more? Click here.

  • ALCON TO LICENSE GOOGLE “SMART LENS” TECHNOLOGY. In a recent press release, Novartis announced that its eye-care division, Alcon, has entered into an agreement with a division of Google Inc. to in-license its “smart lens” technology for all ocular medical uses. The transaction with Google[x] remains subject to anti-trust approvals. Under the agreement, Google[x] and Alcon will collaborate to develop a smart lens that has the potential to address ocular conditions. The smart lens technology involves non-invasive sensors, microchips and other miniaturized electronics that are embedded within contact lenses. Novartis's interest in this technology is focused on helping diabetic patients manage their disease and on those living with presbyopia who can no longer read without glasses.

  • ZEISS UNVEILS DIGITAL LENS TO MEET THE NEEDS OF MOBILE DEVICE USERS. For those born in the 1980s and 1990s, digital technology plays a part in almost every aspect of life—and consequently has a significant impact on vision. Fortunately, Zeiss is taking a new approach to addressing the vision needs of this first generation born into digital technology with the Zeiss Digital Lens as well as a consumer marketing approach designed to raise awareness and drive demand for the product. Digital eye strain affects young and old eyes alike, and according to a Vision Council survey, roughly 70% of U.S. adults experience symptoms as a result of digital device use. The Zeiss Digital Lens is a free-form, customized design that integrates the wide, clear distance view that single-vision wearers demand, with a digital boost of focusing power ranging from +0.50 to +1.25. According to Zeiss, this digital viewing area is optimized for digital devices and is reached with minimal head and eye movement. Get additional details here.

  • FDA CLEARS VICTUS FEMTOSECOND LASER PLATFORM FOR LENS FRAGMENTATION PROCEDURE. Valeant Pharmaceutials International Inc.'s wholly owned subsidiary, Bausch + Lomb, has received 510(k) clearance from the FDA for the Victus Femtosecond Laser Platform for laser-assisted lens fragmentation during cataract surgery. The Victus platform offers a number of different lens fragmentation patterns depending on the cataract grade and user preference. It has also received additional CE marks for Intracor treatment used for flapless intrastromal correction, corneal incisions, penetrating keratoplasty and the creation of intrastromal channel incisions for intracorneal ring segments. For more information, click here.

  • U.S. PATENT COVERS BROMFENAC FORMULATIONS IN DURASITE. The United States Patent and Trademark Office has issued a U.S. Patent No. 8,778,999 covering Bromfenac Non-Steroidal Ophthalmic Compositions Formulated in DuraSite. The allowed patent contains both composition and method of treatment claims that will broadly cover all of InSite's bromfenac product candidates, including BromSite (bromfenac 0.075% ophthalmic solution formulated in DuraSite, ISV-303) for the treatment of inflammation and prevention of pain post cataract surgery. Additionally, bromfenac-containing products in InSite's pipeline covered under this patent include: ISV-101 (bromfenac 0.01%—0.04% ophthalmic solution formulated in DuraSite) for the treatment of dry-eye disease, back-of-the-eye BromSite indications, such as the prevention of cystoid macular edema, as well as the combination of bromfenac and dexamethasone-containing products. InSite has successfully completed two Phase III clinical trials of BromSite and plans to file a New Drug Application with the FDA in the second half of 2014. Visit www.insitevision.com to learn more.
  • NOVABAY ANNOUNCES LAUNCH OF I-LID CLEANSER. NovaBay Pharmaceuticals Inc. recently reported that it will initiate a major marketing campaign and commercialization effort for its new product, i-Lid Cleanser. The campaign will target both optometrists and ophthalmologists, and explain why i-Lid Cleanser is a significant advance in the care of dry eye and blepharitis.
  • ABBOTT TO SELL DEVELOPED MARKETS BRANDED GENERICS PHARMACEUTICALS BUSINESS TO MYLAN. In a statement to the press, Abbott reported that it will sell its developed markets branded generics pharmaceuticals business to Myan for equity ownership of a newly formed entity that will combine Mylan's existing business and Abbott's developed markets pharmaceuticals business, and will be a publicly traded company. The business to be sold operates in Europe, Japan, Canada, Australia and New Zealand and includes approximately 3,800 employees. Abbott does not expect to be a long-term shareholder in Mylan and will retain its branded generics pharmaceuticals business and products in emerging markets. The transaction is expected to close in the first quarter of 2015.
  • NICOX'S MARKETING RIGHTS FOR SJÖ EXPANDED IN NORTH AMERICA. Nicox S.A. has acquired the extension of the rights to market Sjö, an advanced diagnostic panel for early detection of Sjögren's syndrome, to all health-care practitioners in North America. This builds on a June 2013 agreement with Immco Diagnostics Inc. to promote Sjö to eye-care specialists in the United States, Canada, Mexico and Puerto Rico. Under the terms of the expanded agreement, Nicox will have exclusive rights to promote Sjö to all health-care practitioners in North America. Nicox will be responsible for all marketing activities using its existing team, while Immco will carry out the test in its CLIA-approved laboratory in Buffalo, N.Y., and be responsible for regulatory activities and reimbursement. To read more, visit www.mynicox.com/sjo.

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