From the editors of Review of Ophthalmology:
APRIL IS SPORTS EYE SAFETY MONTH
In this issue: (click heading to view article)
Aqueous Humor Protein Dysregulation in PACG
To better understand the pathogenesis of primary angle-closure glaucoma, researchers undertook a comprehensive proteomic analysis of aqueous humor samples from PACG subjects and matched control donors to study pathogenic alterations in AH composition in disease.
They performed quantitative proteomic analyses in AH samples collected from subjects and a matched control cohort with cataracts.
The AH proteome included 1,363 distinct proteins, of which more than 50 percent were differentially expressed in PACG (773 total; 501 upregulated, 272 downregulated). AH from PACG was enriched in atypical collagens and fibronectins, suggesting that the composition of the trabecular matrix was significantly altered in disease. Pathway and cluster analyses revealed that AH protein modulation in PACG was closely associated with biological processes including platelet degranulation, cellular import/export mechanisms and control of protease activity. In addition, critical mediators of oxygen homeostasis and neuronal function in AH were significantly dysregulated in disease, strongly implicating oxidative stress responses in PACG-associated nerve damage.
Researchers wrote that altered AH proteomes in human PACG indicated oxidative stress in the neuronal damage that preceded vision loss. They suggested that identifying key mediators of PACG pathology could yield new prognostic biomarkers and novel targets for future therapeutic interventions.
SOURCE: Adav SS, Wei J, Qian J, et al. Aqueous humor protein dysregulation in primary angle-closure glaucoma. Int Ophthalmol 2019; Apr;39:4:861-71.
Reactivation in Type 3 Neovascularization After Initial Treatment
Investigators evaluated the long-term incidence and timing of reactivation in individuals with type 3 neovascularization who were treated with three monthly anti-vascular endothelial growth factor injections.
A total of 179 individuals (179 eyes) diagnosed with type 3 neovascularization with a dry macula after three monthly anti-VEGF loading injections were included in this retrospective study. After the initial treatment, individuals were followed up without further injection until the first reactivation. Investigators recorded the incidence and timing of the first reactivation and assessed factors predictive of early reactivation (≤ six months after the third anti-VEGF injection). Here were some of the findings:
• During a mean follow-up of 37.5 ±18.8 months, the first reactivation was noted in 145 subjects (81 percent) at a mean of 6.6 ±4.1 months after the third injection.
• In 94 eyes (64.8 percent), reactivation was noted two to six months after the third injection, while in 37 eyes (25.5 percent) it was noted seven to 12 months after the third injection; in 14 eyes (9.7 percent), reactivation was noted after this period of time.
• The incidence of early reactivation was higher in women (p=0.014) and individuals with a thicker choroid (p=0.026).
Investigators found that, in individuals with type 3 neovascularization, almost all reactivation was detected within 15 months of the third anti-VEGF injection, suggesting the need for close follow-up and detailed examinations during this period. They recommended that females with thick choroids be monitored more frequently during this early period.
SOURCE: Kim JH, Chang YS, Kim JW, et al. Long-term incidence and timing of reactivation in patients with type 3 neovascularization after initial treatment.
Graefes Arch Clin Exp Ophthalmol 2019; Apr 1. [Epub ahead of print].
Localization of Corneal Neovascularization Using OCTA
Scientists explored the application of optical coherence tomography angiography in assessing corneal neovascularization (CoNV), and investigated the features of CoNV in eyes with corneal transplantation, as part of a pilot, case series, observational study.
Individuals who underwent corneal transplantation, including penetrating keratoplasty and deep lamellar keratoplasty with or without additional keratolimbal allograft transplantation, were included. All subjects were followed with a series of ophthalmologic exams, including slit-lamp photography, and were imaged with the anterior segment OCTA. The study included 15 eyes of 14 individuals (12 men; mean age of 37.4 ±13.3 years), of which nine eyes had undergone PKP and six had undergone DLKP. Here were some of the findings:
• OCTA was able to clearly identify the features of CoNV in eyes with significant CoNV and to confirm the presence of CoNV in eyes suspected of having it.
• Four types of CoNV (superficial, stromal, fringe and recipient-bed CoNV) were discovered by OCTA based on their location and depth.
• Superficial CoNV was mainly discovered in eyes that had undergone PKP (88.9 ±11.1 percent), while the recipient-bed CoNV, once thought to be located in the host-graft interface, was discovered to grow in the host cornea only in eyes that had undergone DLKP (83.3 ±16.7 percent).
• Comparing the assessment by two masked observers revealed a kappa value of 0.94, indicating excellent agreement.
Scientists concluded that OCTA could be useful to visualize corneal neovascularization, which might be valuable in assessing corneal graft rejection.
SOURCE: Chan SY, Pan CT, Feng Y, et al. Localization of corneal neovascularization using optical coherence tomography angiography. Cornea 2019; Mar 19. [Epub ahead of print].
Port Delivery System with Ranibizumab for nAMD: Ladder Clinical Trial
Researchers analyzed the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration, as part of a Phase II, multicenter, randomized, active treatment-controlled clinical trial.
Participants included individuals diagnosed with nAMD within nine months, who had received ≥2 prior anti-vascular endothelial growth factor intravitreal injections and who were responsive to treatment.
Subjects were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/mL, 40 mg/mL and 100 mg/mL formulations, or monthly intravitreal ranibizumab 0.5 mg injections. Main outcome measures included time to first implant refill assessed when the last enrolled subject completed the nine-month visit, improvements in best-corrected visual acuity and central foveal thickness, and certain safety benchmarks.
The primary analysis population included 220 individuals, in the following breakdown: (using the PDS) 58 subjects in the 10 mg/mL arm, 62 subjects in the 40 mg/mL arm and 59 subjects in the 100 mg/mL arm; and 41 subjects in the monthly intravitreal ranibizumab 0.5 mg arm. Here were some of the findings:
• With the PDS, median time to first implant refill was 8.7 months in the 10 mg/mL arm, 13 months in the 40 mg/mL arm and 15 months in the 100 mg/mL arm.
• At month nine, the adjusted mean BCVA change from baseline was -3.2 Early Treatment Diabetic Retinopathy Study letters in the PDS 10 mg/mL arm, -0.5 ETDRS letters in the PDS 40 mg/mL arm, +5 ETDRS letters in the 100 mg/mL arm and +3.9 ETDRS letters in the monthly intravitreal ranibizumab 0.5 mg arm.
• At month nine, the adjusted mean CFT change from baseline was similar in the PDS 100 mg/mL and the monthly intravitreal ranibizumab 0.5 mg arms.
• The optimized PDS implant insertion and refill procedures were generally well-tolerated.
• After surgical procedure optimization, the postoperative vitreous hemorrhage rate was 4.5 percent (7/157; one event classified as serious).
• Researchers found no evidence of implant clogging.
Researchers determined in the Phase II Ladder trial that the PDS was generally well-tolerated and demonstrated a dose response across multiple endpoints in individuals with nAMD. They found that the PDS 100 mg/mL arm had visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5 mg injections, but with a reduced total number of ranibizumab treatments. Researchers wrote that the PDS had the potential to reduce treatment burden in nAMD while maintaining vision.
Source: Campochiaro PA, Marcus DM, Awh CC, et al. The port delivery system with ranibizumab for neovascular age-related macular degeneration: Results from the randomized phase 2 ladder clinical trial. Ophthalmology 2019; April 1. [Epub ahead of print].
B+L Launches Lotemax SM 0.38%
Bausch + Lomb began distributing its Lotemax SM (loteprednol etabonate ophthalmic gel) 0.38% to U.S. pharmaceutical distributors, after receiving final approval by the FDA on Feb. 22. The new gel drop formulation of loteprednol etabonate was designed with novel SubMicron technology for efficient penetration to key ocular tissues at a low preservative level and a pH close to human tears, the company says. It’s indicated for the treatment of postoperative inflammation and pain following ocular surgery. B+L says that Lotemax SM delivers a submicron particle size and provides two times greater penetration to the aqueous humor as compared with Lotemax Gel (loteprednol etabonate ophthalmic gel) 0.5%. In addition, the company says it was formulated with moisturizing ingredients, a pH close to that of human tears and the lowest BAK preservative percentage in a loteprednol etabonate formulation. Read more.
Oxurion Enrolls Patients for Phase II Trial Evaluating Combination of Anti-PlGF (THR-317) and Anti-VEGF (ranibizumab) for DME treatment
Oxurion announced that all patients were enrolled in its Phase II trial evaluating its THR-317, a humanized antibody against placental growth factor, in combination with anti-VEGF (ranibizumab) for the treatment of diabetic macular edema. A total of 70 individuals were enrolled in the study, ahead of schedule. Topline data from the study are expected by the third quarter of 2019. Read more.
Fera Pharmaceuticals Gets FDA Nod for Avaclyr
The FDA approved Fera Pharmaceuticals’ New Drug Application for Avaclyr (acyclovir ophthalmic ointment) 3% for the treatment of herpetic keratitis. Orphan drug exclusivity was also granted, providing seven years of marketing exclusivity for the product. Fera’s launch plans include finalizing its selection of a commercialization partner to provide physicians and patients access to its therapy. Read more.
RightEye Database Has One Billion Eye-tracking Data Points
RightEye has built an extensive database of more than one billion eye-tracking data points from more than 100,000 patient tests conducted using the RightEye system. Research and health institutions are using the company’s data to examine the eye-brain connection. The anonymized data is providing researchers with a new and deeper understanding of early indicators for neurological issues, which RightEye hopes will help in the development of new treatment options and interventions. Read more.
EyePoint Announces IPO of Common Stock
EyePoint Pharmaceuticals intends to sell shares of its common stock in an underwritten public offering, for which Guggenheim Securities is acting as the sole bookrunning manager. Among other things, EyePoint says it intends to use the net proceeds to fund the commercialization of DEXYCU (dexamethasone intraocular suspension) 9% and YUTIQ three-year treatment of chronic non-infectious uveitis. Read more.
Study: Light Therapy Might Help Premature Babies Avoid Vision Problems
Researchers at Cincinnati Children's Hospital Medical Center discovered a light-dependent molecular pathway that regulates how blood vessels develop in the eye. The findings in the April 1 online edition of Nature Cell Biology suggested that light therapy might help premature infants avoid vision problems. The novel molecular process called the opsin 5-dopamine pathway helps ensure blood-vessel development in the eye is appropriately balanced to prepare it for visual function. Researchers are looking for ways to prevent or treat retinopathy of prematurity and myopia in premature infants. Read more.
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