Lindstrom's Perspective

Patient-centered advances enhance post-cataract surgery regimens

The overall global ophthalmic pharmaceuticals market was estimated to be approximately $30 billion per year by Market Scope in 2018, and it is growing at approximately 5% per year. Corticosteroids remain the most commonly utilized anti-inflammatory drug in ophthalmology, and they have a broad array of indications. Topical steroids represent nearly $1 billion per year of sales in the U.S. alone and, using my best estimate, about $3 billion worldwide.

The most common use of a steroid in ophthalmology is to reduce postoperative inflammation and pain following cataract surgery, and this is the FDA label most new steroid products pursue first. The typical FDA clinical trial evaluates inflammation as measured by anterior chamber cell and flare and pain using a patient-reported outcome pain scale, active pharmaceutical agent vs. vehicle, at approximately 14 days after surgery. Other important indications include the treatment of anterior and posterior uveitis and the management of ocular surface diseases, especially allergy, dry eye, blepharitis, scleritis, the rarer graft rejection, graft-versus-host disease and the like.

Steroids are available as drops, injections and implants. Ophthalmic drugs are available as over the counter without prescription, as branded and unbranded generics, as branded patent-protected products and as custom compounded formulations. In the case of ophthalmic steroids, there are no OTC products, primarily because of the risks of secondary glaucoma, cataract and enhanced infection. This is not true in all fields, as nasal steroid sprays are readily available OTC, and I have seen a few cases of secondary steroid-induced glaucoma from their use. As exemplified by the steroids discussed in the accompanying cover story, the newest patented branded steroids offer potential benefits not previously available. I will disclose that I consult for and/or own equity in three of the four companies discussed in the cover story and that I also consult for and/or own equity in several current or potential future competitors.

The new loteprednol drops offer enhanced corneal penetration, either allowing a reduced concentration to be used to enhance safety or increasing drug concentration in the anterior chamber to enhance efficacy in reducing intraocular inflammation and/or postoperative pain. The Kala loteprednol products also offer a new potential indication, the treatment of episodic flares of dry eye disease, which according to its research occurs four to six times per year. The EyePoint Dexycu and Ocular Therapeutix Dextenza offerings both provide extended release of dexamethasone, the first using an intracameral injection behind the iris and the second a punctal plug that releases drug into the tear film. All ophthalmologists appreciate the challenges associated with patient compliance, and these two new offerings will put perioperative steroid treatment for post-cataract surgery inflammation and pain in the surgeons’ hands, rather than the patients’. We have, of course, had this option for decades through the use of subconjunctival, sub-Tenon’s or intraocular steroid injections or placement of drug release pellets or devices, but for the cataract surgeon, Dexycu and Dextenza offer an easy-to-use FDA-approved extended-release steroid with a label specifically for the reduction of inflammation and pain after cataract surgery. These two drugs will also have pass-through reimbursement, which will essentially make them available to many patients at no charge.

I have been an advocate of intracameral antibiotics for a long time and currently favor a moxifloxacin/dexamethasone/ketorolac formulation compounded by ImprimisRx placed intracamerally on the surface of the eye and by some surgeons subconjunctivally at the end of the case. This has, for me, eliminated the use of a topical antibiotic. The use of Dexycu or Dextenza now provides another opportunity to also eliminate postoperative topical steroids for our patients.

I remain an advocate of topical NSAIDs, which today are fortunately available in one drop per day FDA-approved versions. I have also utilized generic or custom compounded ketorolac topically twice daily for 2 weeks and once per day for up to 6 weeks with good success. So, we now have a reasonable postoperative regimen for the 4 million cataract surgeries performed each year in the U.S. and can reduce patient topical drop usage to one drop a day, or as some have labeled it: “drop a day.” If you are not a NSAID advocate, so-called “dropless” cataract surgery is also now a real option. That, to me, is a significant patient-centered advance that promises to enhance compliance, convenience and cost to the patient.

Disclosure: Lindstrom reports he consults for Bausch Health, Kala Pharmaceuticals, Ocular Therapeutix, ImprimisRx, and several current and potential competitors or those who fund them.

The overall global ophthalmic pharmaceuticals market was estimated to be approximately $30 billion per year by Market Scope in 2018, and it is growing at approximately 5% per year. Corticosteroids remain the most commonly utilized anti-inflammatory drug in ophthalmology, and they have a broad array of indications. Topical steroids represent nearly $1 billion per year of sales in the U.S. alone and, using my best estimate, about $3 billion worldwide.

The most common use of a steroid in ophthalmology is to reduce postoperative inflammation and pain following cataract surgery, and this is the FDA label most new steroid products pursue first. The typical FDA clinical trial evaluates inflammation as measured by anterior chamber cell and flare and pain using a patient-reported outcome pain scale, active pharmaceutical agent vs. vehicle, at approximately 14 days after surgery. Other important indications include the treatment of anterior and posterior uveitis and the management of ocular surface diseases, especially allergy, dry eye, blepharitis, scleritis, the rarer graft rejection, graft-versus-host disease and the like.

Steroids are available as drops, injections and implants. Ophthalmic drugs are available as over the counter without prescription, as branded and unbranded generics, as branded patent-protected products and as custom compounded formulations. In the case of ophthalmic steroids, there are no OTC products, primarily because of the risks of secondary glaucoma, cataract and enhanced infection. This is not true in all fields, as nasal steroid sprays are readily available OTC, and I have seen a few cases of secondary steroid-induced glaucoma from their use. As exemplified by the steroids discussed in the accompanying cover story, the newest patented branded steroids offer potential benefits not previously available. I will disclose that I consult for and/or own equity in three of the four companies discussed in the cover story and that I also consult for and/or own equity in several current or potential future competitors.

The new loteprednol drops offer enhanced corneal penetration, either allowing a reduced concentration to be used to enhance safety or increasing drug concentration in the anterior chamber to enhance efficacy in reducing intraocular inflammation and/or postoperative pain. The Kala loteprednol products also offer a new potential indication, the treatment of episodic flares of dry eye disease, which according to its research occurs four to six times per year. The EyePoint Dexycu and Ocular Therapeutix Dextenza offerings both provide extended release of dexamethasone, the first using an intracameral injection behind the iris and the second a punctal plug that releases drug into the tear film. All ophthalmologists appreciate the challenges associated with patient compliance, and these two new offerings will put perioperative steroid treatment for post-cataract surgery inflammation and pain in the surgeons’ hands, rather than the patients’. We have, of course, had this option for decades through the use of subconjunctival, sub-Tenon’s or intraocular steroid injections or placement of drug release pellets or devices, but for the cataract surgeon, Dexycu and Dextenza offer an easy-to-use FDA-approved extended-release steroid with a label specifically for the reduction of inflammation and pain after cataract surgery. These two drugs will also have pass-through reimbursement, which will essentially make them available to many patients at no charge.

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I have been an advocate of intracameral antibiotics for a long time and currently favor a moxifloxacin/dexamethasone/ketorolac formulation compounded by ImprimisRx placed intracamerally on the surface of the eye and by some surgeons subconjunctivally at the end of the case. This has, for me, eliminated the use of a topical antibiotic. The use of Dexycu or Dextenza now provides another opportunity to also eliminate postoperative topical steroids for our patients.

I remain an advocate of topical NSAIDs, which today are fortunately available in one drop per day FDA-approved versions. I have also utilized generic or custom compounded ketorolac topically twice daily for 2 weeks and once per day for up to 6 weeks with good success. So, we now have a reasonable postoperative regimen for the 4 million cataract surgeries performed each year in the U.S. and can reduce patient topical drop usage to one drop a day, or as some have labeled it: “drop a day.” If you are not a NSAID advocate, so-called “dropless” cataract surgery is also now a real option. That, to me, is a significant patient-centered advance that promises to enhance compliance, convenience and cost to the patient.

Disclosure: Lindstrom reports he consults for Bausch Health, Kala Pharmaceuticals, Ocular Therapeutix, ImprimisRx, and several current and potential competitors or those who fund them.