Read additional news stories:

• OpRegen Cell Therapy Has Positive Data in Geographic Atrophy
  Visual acuity gains were maintained up to 24 months.
• Gemini Geographic Atrophy Drug to Advance Into Phase 2 Trial
  Recombinant form of complement factor H met phase 1 endpoints.
• Wet AMD Patients Prefer PDS Implant Over Injections
  Patients underwent only 2 procedures in 40 weeks.
• Suprachoroidal Drug Delivery Scores Well in Study
  Physician users report the administration technique to be applicable to a range of anatomic and demographic variables.
• IRIS Registry Study Shows Severe Impact of Geographic Atrophy
  Data show that vision loss is often dramatic.
• Adverum Gene-derived Anti-VEGF Proves Highly Durable
  Wet AMD patient goes 92 weeks without retreatment.

IN BRIEF

Research and industry news in retina.

BY JERRY HELZNER, CONTRIBUTING EDITOR

Study Emphasizes Early Detection and Treatment of Wet AMD

■ A large-scale “real-world” study evaluating visual outcomes in patients with wet AMD based on their baseline visual acuity (VA) at time of initial treatment was reported in Ophthalmic Surgery, Lasers and Imaging Retina. Data were compiled from the American Academy of Ophthalmology’s IRIS Registry.

The retrospective analysis looked at 162,902 eyes. Of the eyes presented, 34.3% had 20/40 or better VA at diagnosis. Following treatment initiation, the data showed that the eyes with 20/40 or better VA at baseline maintained a mean VA of 20/40 or better for 2 years. The new data show that although early detection is essential for better visual outcomes, current methods are not detecting wet AMD early enough in more than 65% of patients to maintain functional vision through anti-VEGF therapy.

Ocular Therapeutix AMD Implant Effective in Phase 1

■ Interim data from the phase 1 study for wet AMD being conducted in Australia continues to demonstrate that the OTX-TKI axitinib intravitreal implant has been generally well tolerated with a favorable safety profile. Evidence of biologic activity is demonstrated across the 3 dose groups, as measured by a decrease in subretinal and/or intraretinal fluid. Durability has been seen up to 11 months in 1 subject without the need to rescue. OTX-TKI is a bioresorbable hydrogel implant incorporating axitinib, a small-molecule tyrosine kinase inhibitor with anti-angiogenic properties for the potential treatment of wet AMD and other retinal diseases.

Aura Biosciences Therapy Preserves Vision in Ocular Melanoma

■ Aura Biosciences said its 2-step, light-activated AU-011 intravitreal therapy for ocular melanoma has been shown in a phase 1b/2 trial to preserve an average of 91% of vision in 22 phase 3-eligible patients over a mean period of 13 months. Statistically significant tumor growth rate reduction compared to historical norms has also been achieved in these same patients.

Suprachoroidal administration of AU-011 has recently begun in a small number of patients with a favorable safety profile to date. Aura believes that suprachoroidal delivery will increase the number of treatable patients, reduce intraocular inflammation, and optimize treatment parameters.

Distinguishing Central Serous Chorioretinopathy From Wet AMD

■ Canadian researchers from the University of Alberta have developed a new set of quantitative criteria to differentiate central serous chorioretinopathy (CSR) from wet AMD, which they recently reported in the Journal of VitreoRetinal Diseases. A prospective, observational study was conducted of 56 eyes of patients with a new diagnosis of CSR, wet AMD, or indeterminate presentation. All patients underwent clinical assessment, axial length measurement, enhanced-depth imaging–optical coherence tomography, and intravenous fluorescein angiography. A final consensus diagnosis was derived following review of these factors.

Factors associated with CSR included age ≤70 years, subfoveal choroidal thickness ≥300 mm, dome-shaped neurosensory detachment, retinal pigment epithelial changes, subretinal hyperreflective material, and fibrovascular pigment epithelial detachment. A salient finding of the study is that choroidal thickness is increased in CSR when compared with wet AMD.

Anti-VEGF Highly Effective Against RVO-Related ME

■ Researchers led by Thomas Ciulla, MD, MBA, of the Indiana University School of Medicine, set out to assess visual acuity (VA) outcomes and anti-VEGF therapy intensity in retinal vein occlusion (RVO)-related macular edema (ME). A retrospective study was completed in 15,613 eyes of treatment-naïve patients with RVO-related ME from 2013 to 2019, using the Vestrum Health Retina Database.

In 6 months, in 8,876 eyes with branch retinal vein occlusion (BRVO)-related ME, after a mean of 4.5 anti-VEGF injections, VA increased by 9.4 letters from a baseline of 55.1 letters. In 6,737 eyes with central retinal vein occlusion (CRVO)-related ME, after a mean of 4.6 anti-VEGF injections over 6 months, VA improved by 9.2 letters from a baseline of 37.2 letters. In 1 year, VA gain was similar (BRVO: 7.4 injections, +8.1 letters; CRVO: 7.6 injections, +7.1 letters). In 6 months and 1 year, mean letters gained increased with number of anti-VEGF injections. Patient eyes with baseline VA of 20/40 or better tended to lose VA in 1 year.

Mean change in VA correlated with treatment intensity, but patients with better VA at presentation were susceptible to vision loss, reflecting a ceiling effect. Assessed with the same database, VA gains compared favorably with 1-year VA gains in wet AMD and DME, but exhibited a larger gap when compared with corresponding randomized controlled trials. Findings were reported in the British Journal of Ophthalmology.

Two Conditions That Render Anti-VEGF Ineffective

■ In an NEI prospective study of patients with wet AMD who were receiving both oral supplements (AREDS2 protocol) and anti-VEGF treatment, of the 594 eligible eyes, the number with BCVA ≤20/200 at 2 years was 56 (9.4%). Mean BCVA in this low-vision group was 14.9 letters (SD 12.3; 20/500), vs 70.1 letters (SD 12.8; 20/40) in the larger group.

Of the 55 eyes with color fundus photography (CFP) available at 2 years, 33 (60.0%) were assessed from CFP grading to have central macular atrophy as the principal cause for poor vision. The remaining 22 eyes (40.0%) were assessed to have central subretinal fibrosis. The group with poor BCVA had a higher proportion of non-White participants, lower BCVA 2 years earlier, higher proportion with macular atrophy 2 years earlier, higher proportion with macular hemorrhage, and fewer anti-VEGF injections.

BCVA data and CFP were obtained in a clinical trial environment but related to anti-VEGF therapy given in routine clinical practice. At 2 years after starting anti-VEGF therapy, almost 1 in 10 eyes had BCVA at the level of legal blindness. From CFP grading, the cause of poor vision appeared to be macular atrophy in 60% and subretinal fibrosis in 40%. These data may be useful in understanding the long-term limits to good vision in wet AMD. Findings were reported in the journal Ophthalmology Retina.

Regenxbio Begins DR Trial With Suprachoroidal Delivery

■ Regenxbio announced that the first patient has been dosed in ALTITUDE, a phase 2 trial to evaluate the suprachoroidal delivery of RGX-314 using the SCS Microinjector (Clearside Biomedical) for the treatment of diabetic retinopathy (DR).

“This is our second phase 2 trial using the in-office suprachoroidal delivery approach, which may allow physicians to treat patients with diseases like DR earlier in the disease course,” said Steve Pakola, MD, chief medical officer of Regenxbio, in a news release. “Long-term treatment with anti-VEGF injections has been shown to significantly reduce disease progression and severity of DR, even in patients who are asymptomatic, as well as prevent vision-threatening complications.”

“The SCS Microinjector is designed to provide targeted delivery of the gene therapy to the suprachoroidal space, with broad distribution to the back of the eye and into the retina through a one-time, in-office procedure, which could be an important alternative to current standard of care,” said trial investigator Charles Wykoff, MD, PhD, in a news release.

Novartis Acquires Gene Therapy Startup

■ Novartis has acquired Vedere Bio, adding a new platform for AAV-based delivery of gene therapies and a novel optogenetics program to help reimagine the treatment and prevention of vision loss and blindness. The technologies acquired include light-sensing proteins that can be delivered to cells in the retina and unique, adeno-associated virus (AAV) delivery vectors that enable treatment via intravitreal injection. Together, these assets could expand the number of patients who could be treated for vision loss due to photoreceptor death, including all inherited retinal dystrophies.

The acquired optogenetics technology is designed to work by delivering naturally occurring, light-sensing proteins to specific retinal cells, stimulating the targeted cells to sense and transmit information to the visual processing centers in the brain. This method bypasses photoreceptor cells that may have died in retinal degeneration. Additionally, the novel AAV capsids acquired in the deal allow the optogenetic therapies to be injected intravitreally into the eye. This could potentially be administered by an ophthalmologist in the clinic.

A Severity Score for ROP Based on Deep Learning

■ Researchers from the i-ROP consortium sought to develop a severity score scale for retinopathy of prematurity (ROP) based on deep-learning algorithms derived from 499 selected images. For deep-learning analysis, a total of 6,344 clinical examinations were analyzed. A higher deep-learning-derived vascular severity score (scale of 1-9) was associated with more posterior disease, higher disease stage, and higher extent of stage 3 disease. For a given ROP stage, the vascular severity score was higher in zone I than zone II or III. For a given number of clock hours of stage 3, the severity score was higher in zone I than zone II. Multivariable regression found zone, stage, and extent were all independently associated with the severity score.

The i-ROP group found that a vascular severity scale for ROP appears feasible for clinical adoption; corresponds with zone, stage, extent of stage 3, and plus disease; and facilitates the use of objective technology, such as deep learning, to improve consistency of ROP diagnosis. Findings were published in the journal Ophthalmology.

Lucentis Biosimilar Effective in Phase 3 Trial

■ Samsung Bioepis announced positive 1-year results from the phase 3 study on SB11, a proposed biosimilar to Lucentis (ranibizumab), in patients with wet AMD.

“The 52-week data confirm SB11 has equivalence in efficacy and pharmacokinetics as well as a comparable safety and immunogenicity profile with the reference product,” Hee Kyung Kim, senior vice president and clinical sciences division and regulatory affairs team leader at Samsung Bioepis, said in a news release.

Gene Therapy Trial for XLRP Promising at 12 Months

■ The Janssen Pharmaceutical Companies of Johnson & Johnson announced new and positive 12-month data from the ongoing phase 1/2 trial of its investigational gene therapy for inherited retinal disease X-linked retinitis pigmentosa (XLRP). The data showed that low and intermediate doses were well tolerated and continued to demonstrate statistically significant sustained or increased vision improvement across multiple metrics and modalities.

The primary endpoint of the trial is safety, with secondary endpoints assessing changes in visual function at prespecified post-treatment timepoints. In the dose-escalation phase, at 12 months, 6 of 7 patients in the low (n=3) and intermediate (n=4) doses demonstrated improvement or stability in retinal sensitivity in the treated eye as measured by full-field static perimetry and mesopic microperimetry.

Safety data to date have demonstrated ocular and systemic safety profiles that are anticipated and manageable. In the high-dose cohort (n=3), inflammation was evident in 2 of 3 adults, and measures of visual function were not improved.

Large Breath Shields Best Antivirus Protection

■ New research released during the 2020 virtual annual meeting of the American Academy of Ophthalmology confirms that breath shields offer effective protection, allowing ophthalmologists to safely examine patients during a pandemic. And, size matters: larger shields offer better protection.

The researchers used spray dye to visualize droplets spread when someone coughs or exhales with and without a shield. Researchers tested 3 options: a large breath shield (45 cm x 44 cm), a standard small shield (11 cm x 11 cm), and no breath shield. Large breath shields offered the best protection, stopping droplets from spreading when coughing or breathing. Small shields did not provide adequate protection against droplet spread from a cough.

“We hope that the findings will further encourage the universal use of larger breath shields as an important part of a health care provider’s infection control measures,” said lead researcher Mong-Loon Kuet, MBBChir, FRCOphth, in a news release. The team of researchers conducted a related study in May 2020 using a particle counter, which detects aerosols that are not visible to the naked eye. Both studies suggest larger breath shields are most effective at reducing infectious particle spread.

Janssen Acquires Hemera’s Gene-derived GA Therapy

■ Janssen Pharmaceuticals, Inc., a Johnson & Johnson company, has acquired the rights to Hemera Biosciences, LLC’s investigational gene therapy HMR59, administered as a one-time, outpatient, intravitreal injection to help preserve vision in patients with geographic atrophy. Patients with AMD often have low levels of CD59, a protein that protects the retina from damage caused by an essential part of the body’s natural immune response called “complement.” In geographic atrophy, an overactivity of complement destroys cells in the macula, and results in a relentless progression to blindness. HMR59 is designed to increase the ability of retina cells to make a soluble form of CD59, helping to prevent further damage to the retina and preserve vision.

“Our aim with this novel, single-administration gene therapy is to use our development expertise and deep heritage in vision care to help improve patient outcomes by intervening early, halting the progression to blindness, and preserving more years of sight,” said James F. List, MD, PhD, Janssen’s global therapeutic area head of cardiovascular and metabolism.

A 17-patient phase 1 study of HMR59 for patients with geographic atrophy is complete. A second phase 1 study exploring HMR59 in patients with wet AMD is under way.

Leiters and ECI to Collaborate on Ophthalmic Networking

■ Leiters, an FDA-registered 503B outsourcing provider of hospital and ophthalmology compounded sterile preparations and pharmacy services, has entered into a corporate partnership with EyeConnect International (ECI) in support of its newly created digital ophthalmic clinical networking platform. EyeConnect International’s mission is to create an interactive, online worldwide community of ophthalmologists dedicated to the advancement of the ophthalmology practice and the improvement of patient care.

Norlase Gets Approval for LION Green Laser System

■ Norlase announced the 510(k) clearance from the FDA and the immediate commercial launch of Norlase LION, a green laser photocoagulator fully integrated into a Keeler indirect ophthalmoscope. Unlike other laser indirect ophthalmoscopes that require a fiberoptic connection to a laser source, LION has no fiber tether, is powered by a battery, and utilizes an advanced wireless interface with voice control of parameters. With the new LION, ophthalmologists can experience an untethered, lightweight, and portable laser treatment solution in nearly any setting.

Ocular Therapeutix Gets CPT Code for Drug-eluting Inserts

■ Ocular Therapeutix announced that its application for a Category I CPT procedure code has been granted by an AMA panel. The permanent Category I CPT procedure code will replace the current Category III CPT code (0356T) for the administration of drug-eluting intracanalicular inserts, including Dextenza (dexamethasone ophthalmic insert) for inflammation and pain following ophthalmic surgery. Category I codes normally have a standardized Medicare physician fee schedule, and as a result are anticipated to improve coverage and payment across all payers for procedures performed in both the ASC and physician office settings.

“This is an important milestone toward establishing an appropriate coding and reimbursement environment for our intracanalicular products and in realizing our goal of replacing eye drops for certain conditions,” said Antony Mattessich, president and CEO of Ocular Therapeutix. “The recognition by the AMA that a separate code should be available for the placement of these inserts affirms this novel route of administration.” RP