FDA Approves Glaukos iStent Inject

■ Glaukos has received premarket approval from the FDA for its next-generation iStent inject Trabecular Micro-Bypass System indicated for the reduction of IOP in adult mild-to-moderate primary open-angle glaucoma (POAG) patients undergoing concomitant cataract surgery. According to the company, the iStent inject is the smallest medical device ever approved by the FDA.

The iStent inject is designed to optimize the natural physiological outflow of aqueous humor by creating two bypasses through the trabecular meshwork, the main source of resistance in glaucomatous eyes, resulting in multi-directional flow through Schlemm’s canal. It includes two heparin-coated titanium stents preloaded into an auto-injection system that allows the surgeon to precisely implant stents into two trabecular meshwork locations through a single corneal entry point in a straightforward click-and-release motion. The iStent inject is based on the same fluidic method of action as the company’s first-generation pioneering iStent, which has been implanted in more than 400,000 eyes worldwide since its introduction in 2012.

The FDA approval is based on the iStent inject US IDE pivotal study, a prospective, randomized, multicenter clinical trial of 505 POAG patients randomized to receive iStent inject in combination with cataract surgery (n=387) or cataract surgery only (n=118). The trial data showed that the iStent inject achieved a statistically significant reduction in unmedicated diurnal IOP in patients undergoing cataract surgery at 24 months, as 75.8% of the iStent inject cohort achieved a 20% or greater reduction in unmedicated IOP and the mean unmedicated IOP reduction was 7.0 mmHg for the iStent inject cohort.

Sustained-Release Lumigan Shows Treatment Benefit

■ In a 594-patient phase 3 clinical trial, an investigational, sustained-release version of Allergan’s Lumigan (Bimatoprost SR), formatted as a biodegradable intracameral implant, demonstrated a major treatment benefit in patients with open-angle glaucoma or ocular hypertension. Patients receiving Bimatoprost SR experienced 30% lower IOP over the 12-week primary efficacy period when compared to patients receiving timolol eye drops, meeting the noninferiority endpoint while being well tolerated by most patients. Bimatoprost SR is designed to lower IOP for 4 months, freeing patients from daily eye drop regimens.

“Bimatoprost SR has the potential to be the first sustained-release option of a drop-free therapy for patients who are suffering from glaucoma. This is a real potential paradigm shift,” said Randy Craven, MD, associate professor at Johns Hopkins University School of Medicine, in a news release. Additional safety data from the study and topline results from a second phase 3 clinical trial will be reported in early 2019, with the possibility of a United States marketing application to be filed in the second half of 2019.

Genetic Variants Can Help Predict Glaucoma Risk

■ A study by researchers from King’s College London, University College London, Massachusetts Eye and Ear, and Harvard Medical School has identified 133 genetic variants that could help predict the risk of developing glaucoma. In the study, scientists evaluated 140,000 people drawn from the UK Biobank and EPIC-Norfolk. Eye pressure readings were taken, which were compared with a DNA analysis of each patient to assess how likely it was that they would develop the disease.

By comparing the pressure test results with a genetic analysis of the many common, small variations in DNA that contribute a tiny amount to overall eye pressure, the team identified 133 genetic variants in the DNA of those who had high pressure readings, and so were at highest risk of developing the condition. The genetic variations predicted whether someone might develop glaucoma with 75% accuracy.

“Knowing someone’s genetic risk profile might allow us to predict what risk of glaucoma he or she carries so that in the future we can focus scarce health care resources on those most at risk,” lead Author Dr. Pirro Hysi from King’s College London, said in a news release.

Neuron Protection Seen as Reducing Glaucoma Risk

■ To combat the incidence of glaucoma, researchers at Augusta University in Georgia want to help the neurons in our eyes better protect themselves and get better help from their friends. The researchers are working to see whether agents that activate the innate neuron protector sigma 1 receptor, or S1R, can do both. Kathryn Bollinger, MD, ophthalmologist, glaucoma specialist, and retinal cell biologist, has evidence that a good additional strategy would be directly enhancing protection of neurons in our eyes, called retinal ganglion cells, hopefully by directly activating S1R.

“We may be able to protect the retinal ganglion cells more long term,” says Dr. Bollinger, a faculty member in the Department of Ophthalmology at the Medical College of Georgia and recent recipient of a $1.5 million grant from the National Eye Institute.

S1R stimulation has been shown to protect retinal ganglion cells in other disease models, but this appears to be the first work in glaucoma, Dr. Bollinger says of the protein that is expressed in both neurons and their astrocytes throughout our visual system. Her work over the past year has focused on the impact of activating S1R in the astrocytes.

The new grant is enabling her also to look at whether activating S1R, with existing drugs already used in patients for other reasons, enables neurons to better protect themselves. The high IOP that glaucoma produces inside the eye seems to transform astrocytes, a type of brain cell that provides nutrition and other support to the neurons, into a nemesis that instead releases toxically high levels of substances like nitric oxide and reactive oxygen species.

Dr. Bollinger’s team is further exploring the impact of activating S1R with known agonists like the pain reliever pentazocine and the antidepressant selective serotonin reuptake inhibitors. They are looking at their impact on neuron survival and function and the level of support from protective proteins like brain-derived neurotrophic factor, which aids neuron survival as well as new neuron growth.

MIGS Device Is Promising in Trial

■ iSTAR Medical SA, a medical device company developing novel ophthalmic implants for the treatment of glaucoma, has announced encouraging 6-month results of their first-in-human micro-invasive glaucoma surgery (MIGS) trial for the MINIject device in a standalone setting. Results show MINIject to be safe and highly effective in achieving significant IOP reduction in glaucoma patients. The trial showed that the implantation of MINIject resulted in an average 39% IOP reduction to a mean of 14.2 mmHg at 6 months. In addition, 87.5% of patients were able to discontinue topical medication usage and remained medication-free at 6 months. There were no serious ocular adverse events.

The trial is a prospective, open, international, multicenter study in which a MINIject was implanted in 25 patients with mild-to-moderate, primary open angle glaucoma uncontrolled by topical hypotensive medication. The aim of the study is to assess the safety and performance of the MINIject device measured by IOP reduction under medication from baseline to 6 months. Subsequent safety and performance will be measured up to 2 years post surgery.

iSTAR says the MINIject device provides a safe, effective and sustainable solution to significantly reduce IOP by enhancing aqueous humor outflow from the anterior chamber to the supraciliary space. The company says the MINIject takes a new approach to drainage, which represents a paradigm shift. Unlike other technologies, MINIject uses STAR material, a soft and flexible medical-grade silicone with a microporous, multichannel geometry. The proprietary STAR material has antifibrotic properties, which minimize scarring and maintain implant performance over time, according to the company.

Retina Drug Studied for Potential IOP Lowering

■ Tie2 dysfunction in the conventional outflow pathway has been implicated in glaucoma. Aerpio’s lead drug candidate, AKB-9778, is a small-molecule inhibitor of VE-PTP, a critical negative regulator of Tie2, that is in later-stage clinical development for the treatment of diabetic retinopathy. The purpose of this exploratory analysis was to assess the effect of subcutaneous administration of AKB-9778, compared to placebo, on IOP in patients with diabetic retinopathy.

Pretreatment baseline IOP assessment showed both the study eye and fellow eye of each treatment group to be normotensive and well balanced between treatment groups. Both active AKB-9778 treatment arms achieved statistically significant reductions in IOP in both the study eye and the fellow eye compared to baseline, whereas there was no change in IOP in the placebo arm. In the subgroup of patients with baseline IOP greater than 16 mmHg, a greater IOP reduction was achieved. These findings, presented at the recent ARVO meeting, support evaluation of Tie2 activation by AKB-9778 as a potential approach for IOP reduction in patients with open-angle glaucoma or ocular hypertension.

GonioPen Offers Easier Gonioscopy

■ Scientists at Nanyang Technological University (NTU), Singapore, with clinicians from the Singapore Eye Research Institute, have invented a new “pen camera” that makes it easier for doctors to diagnose patients with glaucoma. Called the GonioPEN, it could help tackle the eye disease with its ability to detect the type of glaucoma in a faster and cheaper manner. It causes negligible discomfort, unlike the current gonioscopes, which are glass scopes that must be pressed against the eye of the patient for clinicians to look at the eye’s drainage canal.

The GonioPEN allows physicians or trained technicians to capture more detailed images of the eye drainage canal with minimal contact at the side of the cornea. Physicians then use software that aids diagnosis to analyze the images. In a recent pilot study, all 20 patients found the GonioPEN more comfortable than the conventional handheld lens used with a microscope. GP