From the editors of Review of Ophthalmology:
JUNE IS FIREWORKS EYE SAFETY & CATARACT AWARENESS MONTH
In this issue: (click heading to view article)
Five-year Treatment Outcomes Following IVR Injections for nAMD
Researchers assessed the real-world, five-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration as part of a retrospective, observational and open-label effectiveness study that included 295 eyes.
The participants included individuals with treatment-naïve neovascular AMD who received intravitreal ranibizumab monthly injections at least three times at the loading phase, followed by further injections pro re nata and follow-up assessments for five years. Outcomes were determined at least five years after the first ranibizumab injection. Here were some of the findings:
• Mean logMAR best-corrected visual acuity at baseline was 0.52.
• The mean BCVA significantly improved after three loading injections; however, it declined gradually.
• The BCVA at one year was significantly better than the baseline BCVA, while the three-year, four-year and five-year BCVA values were significantly lower than the baseline values.
• The average central foveal thickness improved significantly from 366 ±125 μm to 268 ±134 μm (p<
• Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization than in cases with other AMD (p=
Researchers concluded that IVR was well-tolerated in eyes with AMD although they noted that a PRN regimen for AMD might have limited real-world effectiveness for long-term maintenance of improved visual acuity. They added that macular atrophy might occur more frequently in classic CNV. To maintain good vision, researchers suggested that IVR treatment should be started early and performed continuously.
SOURCE: Wada I, Oshima Y, Shiose S, et al. Five-year treatment outcomes following intravitreal ranibizumab injections for neovascular age-related macular degeneration in Japanese patients. Graefes Arch Clin Exp Ophthalmol 2019; May 22. [Epub ahead of print].
Macular Vessel Density Before & After Anti-VEGF Therapy in DR
Investigators evaluated changes in macular vessel density following intravitreal anti-VEGF injection in individuals with diabetic macular edema and proliferative diabetic retinopathy in a retrospective case series.
Optical coherence tomography angiography images from 55 eyes of 35 individuals with either DME (46 eyes) or PDR (nine eyes) were included. Investigators calculated macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP), before and after anti-VEGF treatment. They analyzed longitudinal changes in vessel density following serial anti-VEGF treatment in a subset of eyes. Here were some of the findings:
• Vessel density in the SCP, DCP and TCP wasn’t found to be significantly different after one, two or three intravitreal injections (p>0.05 for all time points).
• Subgroup analyses revealed no significant changes in DME or PDR subgroups (all p>0.05).
• Multivariate analyses revealed no effect on VD measurements of injected anti-VEGF agent type or presence of previous treatment (all p>0.05).
• No correlation was found between the anatomic response of DME to treatment or VD measurements.
Investigators determined that macular vessel density remained statistically unchanged following up to three intravitreal injections of any of the anti-VEGF agents. They wrote that this finding indicated that there might not be an early effect of anti-VEGF treatment on macular vessel density and that anti-VEGF treatment’s effect on macular perfusion might not be directly related to a change in microvascular flow.
Sorour OA, Sabrosa AS, Yasin Alibhai A, et al. Optical coherence
tomography angiography analysis of macular vessel density before and after
anti-VEGF therapy in eyes with diabetic retinopathy. Int Ophthalmol 2019; May
22. [Epub ahead of print].
Changes in OCTA and Disease Activity in Type 3 Neovascularization After Anti-VEGF
Scientists evaluated disease activity in individuals with type 3 neovascularization undergoing anti-vascular endothelial growth factor treatment through image analysis using optical coherence tomography angiography.
Thirty-nine treatment-naive eyes with type 3 neovascularization were included in the retrospective analysis. All individuals were treated with three loading injections of an anti-VEGF agent, followed by further injections as needed. Changes in the type 3 lesion were analyzed through OCTA imaging during 12 months of follow-up. Here were some of the findings:
• The high-flow signal of type 3 neovascularization on OCTA images disappeared in 46.2 percent of eyes (19 of 39) and was persistent in 53.8 percent of eyes (20 of 39) after loading injections.
• A persistent high-flow signal on OCTA after treatment was found at the subretinal pigment epithelium in 65 percent of eyes (13 of 20), deep vascular plexus in 30 percent of eyes (six of 20), and outer neurosensory retina in 15 percent of eyes (three of 20).
• Eyes without lesions on OCTA images received significantly fewer injections (3.7 vs. 5.5; p=0.016) and showed a longer retreatment-free period (mean 7.57 vs. 4.07 months; p=0.002) during the 12-month follow-up than eyes with a persistent high-flow signal on OCTA.
• However, no significant between-group differences were observed in terms of improved visual acuity.
Scientists wrote that individuals with type 3 neovascularization who had no lesions on an OCTA scan after anti-VEGF treatment showed a lower recurrence rate and maintained visual acuity with fewer injections than those with persistent high-flow lesions on an OCTA scan. They wrote that OCTA might provide an additional biomarker for clinical guidance in the treatment and monitoring of disease activity in type 3 neovascularization.
SOURCE: Han JW, Cho HJ, Kang DH, et al. Changes in optical coherence tomography angiography and disease activity in type 3 neovascularization after anti-vascular endothelial growth factor treatment. Retina 2019; May 14. [Epub ahead of print].
OTX-101 Ophthalmic Solution 0.09% for the Treatment of Dry-eye Disease
Researchers evaluated the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of individuals with dry-eye disease, as part of Sun Pharmaceutical’s randomized, multicenter, vehicle-controlled, double-masked, Phase III clinical trial of the drug.
Participants included individuals 18 to 90 years of age with a history and clinical diagnosis of DED, a global symptom score of 40 or more (range: 0 to 100), and a lissamine green conjunctival staining score of three or more and nine or less (range: 0 to 12) in at least one eye.
Eligible subjects entered a run-in period of 14 to 20 days in which all individuals were administered the vehicle twice daily. Those who remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days.
Main outcome measures included efficacy assessments such as signs (unanesthetized Schirmer’s tear test, and corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary endpoint was the proportion of eyes with a clinically meaningful improvement (increase of ≥10 mm) in Schirmer’s test score at day 84. Safety evaluations included adverse events, visual acuity and and intraocular pressure monitoring; and slit-lamp, dilated ophthalmoscopy and fundus exams.
A total of 744 individuals were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). Here were some of the findings:
• The primary end point was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group achieved an increase of 10 mm or more in the Schirmer’s test score at day 84 (OTX-101 0.09% group: 16.6 percent; vehicle: 9.2 percent; p<0.001).
• Significant improvements relative to the vehicle also were observed for corneal (days 28, 56 and 84) and conjunctival (days 56 and 84) staining.
• The global symptom score was reduced from baseline in both treatment groups by approximately 30 percent; however, no significant separation between groups was observed.
• The OTX-101 0.09% formulation was well-tolerated.
• Treatment-emergent AEs were primarily mild in intensity.
The study doctors reported observing clinically and statistically significant improvements in tear production and ocular surface integrity in dry-eye patients treated with OTX-101 0.09%.
Source: Goldberg DF, Malhotra RP, Schechter BA, et al. A phase 3, randomized, double-masked study of OTX-101 ophthalmic solution 0.09% in the treatment of dry eye disease. Ophthalmology 2019; Apr 6. [Epub ahead of print].
Allergan, Sightsavers & the IAPB Announce Initiative to Address Glaucoma in Underserved Areas of The World
Allergan, Sightsavers and the International Agency for the Prevention of Blindness announced a joint initiative—Keep Sight—to prevent glaucoma-related vision loss by building up health-care capacity in low- and middle-income countries with the highest unmet need. The initiative will provide training for health-care professionals to screen at-risk populations, ensure early and accurate diagnosis, and provide appropriate treatment and long-term care in an effort to make a positive impact on people with glaucoma, the consortium says. The first program is due to launch at a high-volume hospital in Nigeria, with the goal of screening 5,000 people, treating 500 patients and providing surgery for 70 patients. Read more.
REGENXBIO Completes Dosing for Phase I/IIa RGX-314 Trial
REGENXBIO completed dosing across all five cohorts in the Phase I/IIa clinical trial of RGX-314 for the treatment of wet age-related macular degeneration. The trial is designed to evaluate the safety and tolerability of RGX-314 as a one-time therapy for individuals with wet AMD who were previously treated with anti-vascular endothelial growth factor injections. REGENXBIO is planning to initiate a Phase IIb trial in wet AMD by the end of 2019 based on the Phase I/IIa trial data and file an Investigational New Drug application for the use of the drug in diabetic retinopathy in the second half of 2019. Read more.
Ocular Therapeutix Misses Primary Endpoint in Phase III OTX-TP Trial
Ocular Therapeutix’s drug-eluting insert to treat glaucoma—an intracanalicular insert that delivers a preservative-free formulation of the drug travoprost for the reduction of intraocular pressure in individuals with primary open-angle glaucoma or ocular hypertension—fell short of meeting the primary endpoint of its first Phase III trial. The OTX-TP intracanalicular insert aimed to reduce average intraocular pressure across a total of nine different time points. But compared with placebo, OTX-TP was only able to statistically meet eight of the nine time points, though the company says it lowered intraocular pressure by 3.27 to 5.72 mm Hg, with the highest levels of reduction seen earlier in the trial. Read more.
FDA Lifts Clinical Hold on Adverum Phase I ADVM-022 Trial
Adverum Biotechnologies announced that the FDA lifted its clinical hold on ADVM-022 for the second cohort in the company’s OPTIC Phase I trial for wet age-related macular degeneration, allowing dose escalation to 2 x 1012 vg/eye. This dose would be three times higher than the dose of 6 x 1011 vg/eye evaluated in the first cohort. However, based on the robust preliminary anatomical response observed to date in the first cohort (n=6), Adverum says it will begin dosing the second cohort at a lower dose of 2 x 1011 vg/eye, three times lower than the dose used in the first cohort. Read more.
Lacrivera Introduces Synthetic Absorbable Lacrimal Plugs
Lacrivera launched the Vera180 Synthetic Absorbable Lacrimal Plugs, designed to provide extended temporary occlusion lasting approximately 180 days. According to the company, the plugs are ideal for treatment of post-surgical dry eye and for treating the dry-eye components of various ocular surface diseases, including contact lens intolerance. Made of poly-p-dioxanone, they are available in sizes of 0.2 mm, 0.3 mm, 0.4 mm and 0.5 mm, and packaged in single-pair and 10-pair boxes (20 plugs). Learn more.
New Cleanser Available
Akorn Consumer Health recently released TheraTears SteriLid Antimicrobial Eyelid Cleanser and Facial Wash, which the company says is the first eyelid cleanser to be FDA-accepted as a medical device allowed to make antimicrobial claims. Akorn says the device’s 0.01% hypochlorous acid, 2-oz. formula kills 99.9 percent of bacteria within 30 seconds, but is pH-balanced to be gentle on the eyelids. The company says the product is available in retail stores such as Rite Aid, CVS and Walgreens, as well as through Amazon and U.S. eye-care professional offices. Read more.
Revenio (Icare) to Acquire Centervue
The Revenio Group signed an agreement to purchase CenterVue, a global supplier of ophthalmic devices. Revenio says CenterVue’s retinal imaging innovations will enable its product portfolio to expand beyond glaucoma into retinal diseases such as diabetic retinopathy and age-related macular degeneration. Read more.
Review of Ophthalmology® Online is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 11 Campus Boulevard, Newtown Square, PA 19073.
To subscribe to other JMI newsletters or to manage your subscription, click here.
To change your email address, reply to this email. Write "change of address" in the subject line. Make sure to provide us with your old and new address.
To ensure delivery, please be sure to add firstname.lastname@example.org to your address book or safe senders list.
Click here if you do not want to receive future emails from Review of Ophthalmology Online.
Advertising: For information on advertising in this e-mail newsletter or other creative advertising opportunities with Review of Ophthalmology, please contact sales managers James Henne or Michele Barrett.
News: To submit news or contact the editor, send an e-mail, or FAX your news to 610.492.1049