Intravitreal injections up — so are endophthalmitis cases

By René Luthe, senior editor

The use of intravitreal injections as treatment for retinal disease has increased in recent years, and with it, the prevalence of endophthalmitis. The authors of a study in OM’s sister publication, Retinal Physician, review which practices prevent the problem (and have the data to prove it) and which don’t (www.retinalphysician.com/issues/2018/march-2018/reducing-endophthalmitis-risk-following-intravitre ).

IT DOESN’T HAVE TO BE INEVITABLE

The treatment of exudative macular degeneration, retinal vein occlusions, choroidal neovascularization and diabetic retinopathy all are treated with intravitreal agents, note study authors Matthew R. Starr, MD, and Sophie J. Bakri, MD (guest editor for OM’s July issue).

And, while the incidence of endophthalmitis following intravitreal injections is low, its prevalence is growing due to the sheer volume of intravitreal injections administered now compared to 10 years ago.

Drs. Starr and Bakri review what the literature shows regarding the efficacy of precautions taken before, during and after injection. Their findings include the following:

PRE-INJECTION MANAGEMENT

Regarding the use of topical antibiotics before intravitreal injection, they note recent research that the practice does not decrease the incidence of endophthalmitis following the injection. Further, the practice may even foster drug resistance in the host flora.

As for the setting in which the injection occurs, investigators find no significant difference in endophthalmitis rates between an office setting vs. OR. The greater convenience for both patient and physician, as well as the lower cost associated with the office setting, make it the preferable setting for many.

Although patients frequently mistake irritation and contact dermatitis as allergy, the authors point out that there has never been a reported case of anaphylaxis following conjunctival application of povidone-iodine before an intravitreal injection.

Because povidone-iodine is critical to preventing endophthalmitis following intravitreal injections, physicians must use caution when determining whether patients have a true allergy.

DURING THE INJECTION

At this point, the authors say, some aspects of the sterile technique are not supported by data. There is limited evidence for the use of sterile gloves or a sterile drape, for instance.

The data seem to support the use of a mask, however, and prohibitions on speaking during the procedure. As for antibiotic use, the authors note that it is no more warranted than it is in the pre-injection setting. They cite the Diabetic Retinopathy Clinical Research Network’s finding that there is no reduced risk of endophthalmitis with topical antibiotics during or after an intravitreal injection.

Ocular-surface preparation with povidone-iodine has a consensus of providers endorsing it as “the most important step in preventing endophthalmitis following an intravitreal injection.” There is no consensus, however, for the best method of povidone-iodine application.

Also reviewed is the use of lid scrubs and speculums to prevent the lids and lashes from touching the injection site. The article includes a table of guidelines from a 2014 expert panel on intravitreal injection technique and endophthalmitis prevention. OM

EyeGate awaits FDA’s verdict on amended IDE

By OM staff

EyeGate Pharmaceuticals will know soon whether it can start a second pilot study of EyeGate OBG, or ocular bandage gel. In April, the FDA accepted its amended investigational device exemption (IDE).

The agency asked for more information regarding manufacturing processes, specifically about sterility; clarification on some earlier submitted data; and changes to documents regarding the manufacturing process. EyeGate has begun addressing the questions and anticipates submitting a second amendment in July. The agency then has 30 days to respond. If approved, the company plans to initiate this second pilot study in PRK patients in Q3 with top-line data reported in Q4. The gel, a cross-linked thiolated carboxymethyl hyaluronic acid (CMHA-S) platform, is designed to accelerate re-epithelization of large corneal epithelial flaws and weaknesses.

The company says the high concentration (0.75%) of crosslinked HA serves as a hydrating protectant and lubricant that facilitates acceleration of corneal re-epithelialization. In the anticipated pilot study, patients will receive the gel after undergoing PRK.

EyeGate has already conducted a pilot study to evaluate the gel’s safety and efficacy. In a randomized, open-label, prospective study, 39 subjects receiving bilateral PRK had both eyes randomized to either OBG alone, administered QID; OBG (QID) and a bandage contact lens (BCL); or a BCL with artificial tears. Patients treated with OBG in arm 1 had a faster recovery time compared to the comparison and control groups. OBG demonstrated accelerated wound healing vs standard of care in roughly 55% more patients as measured as wounds closed on Day 3.

Based on this pilot PRK study, the company says this HA eyedrop could expand the number of options now available for improving ocular wound care, healing and regenerative medicine for a variety of corneal injuries.¹ OM

REFERENCE

1. Durrie DS, Wolsey D, Thompson V, et al. Accelerating Re-Epithelialization After Photorefractive Keratectomy With an Ocular Bandage Gel. J Cataract Refractive Surgery. Accepted and in press 2018.

pSivida, Icon Bioscience, merge as EyePoint Pharmaceuticals

By Robert Stoneback, associate editor

In an eventful March for pSivida Corp., the company acquired Icon Bioscience, Inc., manufacturer of Dexycu (dexamethasone intraocular suspension) 9%; learned that the FDA accepted its new drug application for Durasert; and rebranded itself as EyePoint Pharmaceuticals, Inc.

And in February, the FDA approved Dexycu, which, according to EyePoint, is the first long-acting intraocular product designed for treatment of postoperative inflammation. Dexycu is delivered via Icon’s proprietary Verisome drug-delivery platform, which allows for a single injection that releases over time.

EyePoint’s focus is on inflammatory disease states; extended-release treatments; and strategic mergers and acquisitions. It has relationships with Alimera Sciences, Bausch + Lomb and Nicox.

Last year, EyePoint signed an agreement with a pharma house, as of yet unnamed, to develop two glaucoma therapies using EyePoint’s sustained release technology.

“A key focus … during 2017 [was] to expand the number of development collaboration agreements with other drug manufacturers, and this is the second such agreement during 2017,” said Nancy Lurker, president and CEO in a prepared statement.

Dexycu was the subject of a placebo-controlled Phase 3 trial designed to assess the percentage of patients achieving total anterior chamber cell (ACC) clearance by day 8 postsurgery. The result: 60% of the active group achieved total clearance, while 20% of the placebo group achieved total clearance.

The most commonly reported adverse reactions to Dexycu, in up to 15% of participants, included increases in IOP, cornea edema and iritis.

In other developments for EyePoint, the FDA accepted its new drug application in March for its Durasert micro-insert for treatment of noninfectious posterior segment uveitis. Its Prescription Drug User Fee Act (PDUFA) date is Nov. 5. If approved, EyePoint expects to launch Durasert, designed to last three years, in the first half of 2019.

A Phase 3 trial for Durasert involved 153 patients with posterior segment uveitis; it found a mean increase of IOP of 2.0 and 0.0 mm Hg at 12 months over a baseline IOP of 13.3 and 13.1 mm Hg for Durasert and sham, respectively.

Patients requiring IOP-lowering therapy at any time during the first 12 months of follow-up were 50.5% for Durasert and 51.9% for sham. Only one patient, assigned to Durasert, required IOP surgery during the first 12 months of follow-up. This was the second, positive-results Phase 3 trial for Durasert, the company says. OM

Cataracts, refractive error, top global causes of blindness and vision impairment

Uncorrected refractive error and cataracts top the global causes of vision impairment and blindness, according to an analysis published in The Lancet.

The following charts compare the numbers in the most recent research, including statistics from 1990 and projections for 2020,¹ to a previous Lancet study that measured causes of impairment and blindness in 2010.²

REFERENCES

1. Flaxman SR, Bourne RRA, Resnikoff S, et al. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob Health. 2017;5:e1221-e1234.
2. Bourne RR, Stevens GA, White RA, et al. Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health. 2013;1:e339-349.