Macular Hole Surgery and Face-down Posturing
Is it really necessary in FTMH patients?
BY JERRY HELZNER, CONTRIBUTING EDITOR
■ Noting that the need for face-down posturing following surgery for full-thickness macular holes (FTMH) larger than 400 µm) remains “the focus of debate,” researchers from Southampton University Hospital in the United Kingdom conducted a retrospective analysis of 220 consecutive patients with FTMH.
All patients underwent vitrectomy, internal limiting membrane peel, and isovolumetric gas tamponade. Phakic patients underwent phacoemulsification and IOL, even in the absence of visually significant cataract. Patients were not asked to posture but were to avoid lying supine for a week. Demographics, as well as preoperative and postoperative complications, were recorded. The size of the hole and postoperative closure were assessed using OCT.
The mean age of patients was 70 years old (range 45-93), and 162 patients (74%) were female. Macular hole size was small (<250 mm) in 36 patients (16%), medium (250-400 mm) in 77 patients (35%), and large (>400 mm) in 107 patients (49%). Primary success (macular hole closed at 3 months after a single procedure) was achieved in 93.5% of patients. Primary success rate was significantly higher in holes <400 µm (97%) compared with holes >400 µm (90%). Success rate did not vary according to age or gender.
The researchers concluded that macular hole surgery is highly successful without face-down posturing. Even in holes larger than 400 mm, “primary success rates in our study are comparable to surgery with posturing.”
The researchers presented their findings at the recent ARVO meeting under the title “Posturing is not required after macular hole surgery.”
■ Tyrogenex studies oral treatment for wet AMD. Tyrogenex (West Palm Beach, FL) said it has initiated a phase 2 clinical trial for its X-82 anti-VEGF/anti-PDGF oral therapy for patients previously treated for wet AMD. The 132-patient, 52-week “APEX” study, to be conducted at 20 US and five UK sites, has dual endpoints of improved visual acuity and a reduction in anti-VEGF injections.
A recently completed phase 1 trial of the tyrosine kinase inhibitor X-82 showed that 24 of the 27 previously treated subjects who completed the 24-week study needed no anti-VEGF rescue during the study period. The majority maintained or improved their baseline visual acuity.
■ Allegro begins PVD-DR study for Luminate. Allegro Ophthalmics, LLC (San Juan Capistrano, CA), has begun enrolling patients in a phase 2 clinical trial to evaluate the safety and efficacy of its integrin peptide therapy candidate Luminate (ALG-1001) in inducing posterior vitreous detachment (PVD) in patients with nonproliferative diabetic retinopathy.
“We have already seen good evidence that Luminate can induce PVD in patients with diabetic macular edema,” said Baruch Kuppermann, MD, PhD, chief of the Retina Service and vice-chair of Academic Affairs at the Gavin Herbert Eye Institute, University of California Irvine School of Medicine. “This is an important study to broaden and confirm our understanding of this nonsurgical option for patients with mild to moderate nonproliferative DR who may potentially proceed to vision-threatening disease over time.”
Luminate is also being studied as a potential treatment for wet AMD, DME, and VMT.
■ Spark licenses Clearside microinjector technology. Spark Therapeutics, Inc. (Philadelphia) and Clearside Biomedical, Inc. (Alpharetta, GA) have entered into an option agreement under which Spark acquired exclusive rights to license Clearside’s microinjector technology to deliver gene therapies to the back of the eye. Under the agreement, the companies will explore the feasibility of using Clearside’s microinjector technology to deliver viral vectors to the choroid and the retina through the suprachoroidal space (SCS).
If successful, this technique could create a differentiated alternative to subretinal or intravenous administration for future gene therapy applications, potentially broadening the range of conditions treatable through gene therapy.
OCT Angiography Seen as Breakthrough Technology
A noninvasive method to detect eye abnormalities
■ New technology invented by researchers at Oregon Health & Science University’s Casey Eye Institute can improve the clinical management of the leading causes of blindness. The researchers say optical coherence tomography (OCT) angiography could largely replace current dye-based angiography in the management of these diseases. The research was published recently in the Proceedings of the National Academy of Sciences (PNAS).
OHSU researchers found that OCT angiography has considerable advantages over conventional techniques for the diagnosis and management of macular degeneration, diabetic eye disease, and glaucoma.
“This is a significant breakthrough technology that could fundamentally change the way ophthalmologists diagnose and care for patients with retinal vascular diseases that cause blindness,” said David Wilson, MD, director of the Casey Eye Institute. “It will also allow us to diagnose patients earlier, permitting more timely treatment to avoid irreversible loss of vision.”
OCT angiography has been in development for several years in a few centers around the world. The key breakthrough achieved by Casey researchers Yali Jia, PhD, and David Huang, MD, PhD, was an algorithm called “split-spectrum amplitude-decorrelation angiography” (SSADA) that improved the quality of OCT angiography.
“We worked very hard to bring this new technology to clinical use only three years after its invention,” said Dr. Jia.
The OCT angiography used in the study is a noninvasive three-dimensional alternative to conventional angiography. It does not require injections and allows clinicians to measure vascular density and blood flow in vessels in a quantitative manner. This provides new information useful for clinical diagnosis and management.
Conventional dye-based angiography produces a two-dimensional image that cannot be evaluated quantitatively. It also is an invasive procedure that can cause nausea and vomiting and rarely anaphylaxis, a serious allergic reaction.
“The new OCT angiography will be much less invasive for patients. As a result, it is ideal for screening patients for disease and routine checkups to see if treatments are working,” said Dr. Huang. “I believe this technology will be used much more frequently than conventional dye-based angiography because it is faster, better, safer, and cheaper. This will also surely lead to better management of eye diseases.”
■ Ophthotech completes initial phase 3 recruitment. Ophthotech (New York, NY) said it has completed patient enrollment for the first of three large-scale phase 3 clinical trials in wet AMD. The initial trial will assess the efficacy of the company’s proprietary anti-PDGF agent Fovista in combination with Lucentis (ranibizumab, Genentech) compared to ranibizumab monotherapy.
The company said a second large-scale phase 3 trial of the Fovista/ranibizumab combination compared to ranibizumab should be fully recruited by the end of September. A third phase 3 study, currently recruiting, will assess the efficacy of Fovista and Eylea (aflibercept, Regeneron) versus aflibercept monotherapy.
■ Regeneron reports strong Eylea sales growth. Regeneron (Tarrytown, NY) said US sales of its Eylea intravitreal therapy for retinal diseases increased 51% on a year-over-year basis to $541 million in the first quarter of 2015. Worldwide sales of Eylea rose 44% to $833 million.
The company said it now expects US Eylea sales to grow by 30% to 35% for full-year 2015 when compared to 2014. It had previously estimated 2015 US sales growth at 25% to 30%.
■ Argus II has Saudi distributor. Second Sight Medical Products (Sylmar, CA) has signed an exclusive agreement with Gulf Medical to distribute and support the Argus II retinal prosthesis in Saudi Arabia.
Gulf Medical, which is one of the largest medical supply companies in the region, will be in charge of executing in-country management of all aspects of Second Sight’s technology, including programming, importation, supply, and surgical support.
Second Sight also says it implanted 19 Argus II devices in the first quarter of 2015, the highest number for any quarter in company history. Second Sight now has 25 implanting centers and says it continues to add more sites.
Lucentis Plus Dex Reduces AMD Retreatments
“Should be considered in selected cases.”
■ Researchers from the Medical University of Vienna set out to determine whether the addition of dexamethasone in the form of the Ozurdex (Allergan) implant could reduce the number of anti-VEGF retreatments in certain wet AMD patients.
The researchers selected 38 patients (40 eyes) who had been receiving regular anti-VEGF injections of ranibizumab (Lucentis, Genentech) for approximately one year. Half of these patients continued on ranibizumab monotherapy while the other half were given the dexamethasone implant in addition to their anti-VEGF injections.
At four weeks, 14 of the monotherapy patients met the criteria for retreatment while only seven of the patients on combination therapy met the same criteria. At eight weeks, 17 of the monotherapy patients had received retreatment while only eight of the patients on combination therapy required another anti-VEGF injection.
At 12 months, three patients from the overall study group required medication for increased IOP and four of the patients on combination therapy were referred for cataract surgery. Only one patient in the anti-VEGF monotherapy cohort was referred for cataract surgery.
The researchers concluded that the anti-VEGF and dexamethasone combination was effective in delaying the need for anti-VEGF retreatments and that the combination “should be considered in selected cases.”
The study was presented at the recent ARVO meeting under the title “Role of additional dexamethasone treatment for management of persistent neovascularization secondary to age-related macular degeneration.”
■ Ozurdex duration of efficacy study. Noting that the duration of action of the Ozurdex sustained-release dexamethasone (Allergan, Irvine, CA) has been “a subject of controversy,” researchers from the University of Udine (Italy) conducted a 40-eye study. They sought to determine the time period that a single implant remains effective in patients with macular edema associated with various forms of retinal vein occlusion.
Although individual responses varied, the researchers found that the mean effectiveness for the initial treatment was 190 days, and the mean effectiveness for retreatments was 150 days.
The researchers suggested that Ozurdex retreatment should be administered on a PRN basis, with monthly follow-ups beginning at month three.
Implanting Ozurdex is an office-based procedure. A number of patients have received multiple Ozurdex implants for a range of serious retinal diseases, including macular edema, DME, and edema due to noninfectious posterior uveitis.
The researchers presented their findings at the recent ARVO meeting under the title “Ozurdex for macular edema due to retinal vein occlusion: what is the duration of action?”
■ Wide range of responses to anti-VEGF therapy. Three retina specialists from Northwestern University Medical Center (Chicago, IL) assessed the responses of 331 eyes to multiple injections of anti-VEGF therapy over a four-year period from July 2010 to July 2014. Their aim was to identify subgroups of patients with wet age-related macular degeneration and their response to treatment with anti-VEGF agents.
During the study period, 170 eyes maintained vision within two lines of baseline, 56 eyes lost more than two lines, and 66 eyes gained more than two lines.
Of the eyes that gained more than two lines, 16 received fewer than five injections and 17 eyes received more than 20 injections. Of the eyes that lost more than two lines, 21 received more than 20 injections.
The researchers concluded that a broad range of individual responses to anti-VEGF therapy is possible, which poses “a significant challenge” to physicians planning treatment.
The study was presented at the recent ARVO meeting under the title “Patterns of response to anti-VEGF treatment in a large urban cohort of patients with neovascular age-related macular degeneration.”
Neurotech’s Sustained-release Shows Promise
Best gains were in double-implant cohort.
■ One of the first sustained-release treatments to be studied in wet AMD is the NT-503 encapsulated cell therapy implant from Neurotech (Cumberland, RI), which delivers a continuous therapeutic dose of a VEGF receptor for up to two years.
In a multinational dose-escalation study involving researchers from the United States, Mexico, and Israel, 26 patients received a single NT-503 implant and 21 patients received two NT-503 implants.
At 20 months, the median BCVA increase in the double-implant group was 10 letters, with a median improvement in macular thickness of 170 µm. Improvement in the single-implant group was not as great, with 11 of the 26 patients in that cohort requiring rescue therapy. Only four of the 21 patients in the double-implant group required rescue. No patients discontinued treatment.
The research was presented at the recent ARVO meeting under the title: “Interim results of a dose-escalation study of NT-503 encapsulated cell therapy for the treatment of choroidal neovascularization in AMD.” RP
■ Safety of resident-performed intravitreal injections. Researchers at the Penn State Milton S. Hershey Medical Center set out to investigate the safety profile of intravitreal injections performed by ophthalmology residents.
To do so, they reviewed a retrospective consecutive series of 500 intravitreal injections performed between September 2009 and March 2014 at the Lebanon Veterans Affairs Medical Center by ophthalmology residents for patients with wet AMD, diabetic macular edema, or macular edema associated with retinal vein occlusion.
No patient in this study developed endophthalmitis, traumatic cataract, uveitis, retinal tears, vitreous hemorrhage, or retinal detachments.
Three patients (2.4%) with preoperative pigment epithelial detachments developed retinal pigment epithelial tears following intravitreal injection. All three patients developed RPE tears within three months of receiving intravitreal injection. These results are similar to those reported in the literature.
The researchers concluded that, with appropriate training and supervision, ophthalmology residents can perform intravitreal injections with a similar safety profile to that reported in series of intravitreal injections performed by retina specialists. They said larger studies are warranted to confirm these preliminary findings.
The study was presented at the recent ARVO meeting under the title “Safety of intravitreal injections performed by ophthalmology residents.”
■ Looking for the “ideal” vitreoretinal surgeon. At the annual Massachusetts Eye and Ear Vitrectomy Course, 27 vitreoretinal surgical attendings and 20 first-year vitreoretinal surgical fellows were asked to fill out a survey listing 24 positive characteristics that a vitreoretinal surgeon could possess.
The fellows were asked to pick the five most important positive characteristics that a fellow could possess (ranked 1 to 5) and also the five most important positive characteristics that an attending could possess (ranked from 1 to 5). The attendings were only asked to list the five most important positive characteristics that a fellow could possess.
Interestingly, the fellows saw the top two positive qualities for attendings to be “passionate about work” and “skillful communicator,” while the attendings considered the top two ideal qualities for fellows to be “good judgment” and “passionate about work.” Fellows listed the top two qualities for themselves as “integrity” and “professionalism.” They ranked “patience” as high on their list as positive qualities for attendings.
The answers indicated that the fellows prized teaching skills in their evaluation of attending physicians, while attendings praised fellows who are capable of making sound decisions.
The survey results were presented at the recent ARVO meeting under the title “Qualities of the ideal surgical retina fellow and attending.”