Gene therapy, dry eye, refractive errors, retinal disease and microinviasive glaucoma surgery are key therapeutic areas in ophthalmology that have had productive pipelines, with more on the way. At the annual Oph-thal-mology Innovation Summit be-fore the American Academy of Oph-thalmology annual meeting, OIS chair Emmett Cunningham Jr., MD, PhD, MPH, reported on Food and Drug Administration approvals of ophthalmology products in the past year—which he characterized as “a banner year”—and on drugs and devices that are expected to take significant steps toward approval in 2019. He focused on the following: 
• Gene therapy. “If you follow this space you know gene therapy is active generally, but it’s particularly active in ophthalmology,” Dr. Cunningham said, noting that 16 companies are pursuing gene therapy programs in the space. He also cited a recent New England Journal of Medicine editorial in which FDA Commissioner Scott Gottlieb, MD, stated the agency is reviewing more than 700 active investigational new drug applications.¹ “You can see that gene therapy is valued at more than a 200 percent premium over the markets in the 12-month period that we’ve followed,” Dr. Cunningham said. “The world likes gene therapy. It’s come of age.”  
•  Dry eye. Six new dry-eye candidates are in Phase III studies, nine others are in Phase II, and more are in the pre-clinical phase. 

Researchers took aim at dry eye, according to presentations at this year’s OIS meeting.

Five investigative agents seem most promising, Dr. Cunningham noted: loteprednol etabonate ophthalmic solution, for which Kala Phar-ma-ceuticals submitted a new drug application in October; TOP1630, a nonsystemic kinase inhibitor (TopiVert), for which a 200-patient Phase IIB trial is scheduled to start early next year; Aldeyra Therapeutics’ Reproxalap, for which a Phase III trial is due to launch in 2019; OC-02 (Oyster Point Pharma), a nicotinic acetylcholine inhibitor delivered intranasally that depolarizes the trigeminal nerves; and the PAD MC2-03 technology-based cyclosporine eye drop by MC2 Therapeutics, now in a Phase II/III trial. 

Expect more options for dry-eye patients in the future. “There are literally three dozen companies in the dry-eye space that are active and advancing. It’s going to become a very complex and competitive market, and how that falls out is going to be hard to predict,” Dr. Cunningham said.
• Refractive errors. Pharmacotherapies for presbyopia and myopia represent the “holy grail” in ophthalmology, Dr. Cunningham noted. Novartis, Allergan, Orasis, Presbyopia Therapies and Viewpoint Therapeutics are all pursuing programs in presbyopia. Nevakar, Sydnexis and Eyenovia have candidates for myopia. “If presbyopia is a mega-market, [myopia] is twice that and growing,” Dr. Cunningham said, noting that 2 billion people worldwide have presbyopia and 5 billion are projected to have myopia by 2050.  
• Retinal disease. Albeit a “mature field,” promising programs for treatment of age-related macular degeneration include brolucizumab (Novartis); the Port Delivery System with ranibizumab and faricimab bispecific antibody (Roche/Genentech); sunitinib tyrosine kinase inhibitor (Graybug Vision); the VEGF-C/D inhibitor OPT-302 (Opthea); RGX-314 (RegenXBIO); and the topical anti-VEGF platform PAN-90806 (PanOptica). Three can-didates to treat diabetic macular edema—faricimab, luminate (Allegro Ophthalmics) and the small-molecule Tie-2 inhibitor AKD-9778 (Aerpio Therapeutics)—are in Phase II or III trials. 

On the device side, Dr. Cunningham said the FDA has reduced review times of 510(k) applications by half in the past year, according to information the agency supplied. Minimally-invasive glaucoma surgery (MIGS) has been active, with FDA approvals of the iStent inject (Glaukos) and Hydrus Microstent (Ivantis) in the past year—and the voluntary withdrawal of the CyPASS microstent (Alcon). Two MIGS devices—MicroShunt (Santen) and iStent SUPRA (Glaukos)—are in clinical development. He noted that MarketScope projects the number of MIGS procedures to more than double to 584,000 by 2023.

Two devices that received approvals in the past year were also discussed: TrueTear intranasal tear stimulator (Allergan and Oculeve) and IDx-DR (IDx), the first FDA-approved autonomous artificial intelligence-based diagnostic device, which is designed for screening for diabetic retinopathy. 

“AI is a big deal and it’s going to totally transform our world,” Dr. Cunningham said. “We’ll all remember this approval for years to come. It will be very important.” 

 

^{1. Collins FS, Gottlieb S. The next phase of human gene-therapy oversight. N Engl J Med 201;379:1393-1395.}

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Astigmatism Approvals
The fall saw two new approvals for the correction of patients’ astigmatism.

Staar Surgical finally secured approval for myopic astigmatism treatment with its Visian ICL phakic intraocular lens. The Visian is implanted in the posterior chamber.

With the approval, the Visian’s treatment parameters have expanded to the following:
• the correction of myopic astigmatism with a spherical equivalent ranging from -3 to ≤ -15 D (in the spectacle plane) with cylinder of 1 D to 4 D in the spectacle plane; and
• the reduction of myopic astigmatism with spherical equivalent ranging from greater than -15 to -20 D (in the spectacle plane) with cylinder of 1 to 4 D in the spectacle plane.

Visian patients must have an
anterior chamber depth of 3 mm or greater when measured from the corneal endothelium to the anterior surface of the crystalline lens, and a stable refractive history (i.e., refractions that are within 0.5 D of each other for both spherical equivalent and cylinder for one year prior to implantation).

In addition to Staar’s astigmatism approval for its Visian ICL, Carl Zeiss Meditec received approval to correct astigmatism with its femtosecond-laser-based small-incision lenticule extraction procedure. 

SMILE consists of using the Visumax laser to create a lenticule of tissue within the cornea, which is then removed via a side cut. The removal changes the patient’s refraction and corrects the refractive error. One of the initial limitations of SMILE when it was first approved, however, was its inability to
correct a patient’s astigmatism. Now, however, it’s been approved to treat between -0.75 and -3 D of astigmatism, broadening its usefulness.  REVIEW

Corrections

In the October feature, “Solo Practice: Can You (Still) Go It Alone?” Alpharetta, Georgia, ophthalmologist Ajit Nemi, MD, MBA, was incorrectly referred to as “Anjit,” and his practice’s correct name is “Lotus Vision,” not “Lotus Eye.” In the November feature, “Making the Most of Corneal Cross-linking,” reference was made to the FDA’s limited approval of “epi-on” cross-linking; the approval in question was for “epi-off.” In November’s Technology Update, the Argus II requires a vitreous, not a retinal, detachment. The Alpha AMS device requires a power cable, contrary to what is stated in the article. Review regrets the errors.