Advances in drug delivery: Less is more
New formulations and delivery vehicles improve patient compliance, ocular surface toxicity, outcomes and patient experiences.
The world of perioperative medications associated with cataract surgery for the premium surgeon is evolving rapidly.
We have gone from the days of finally having a topical NSAID eye drop to now having it as a once-daily brominated formulation with greater potency (Prolensa, Bausch + Lomb; BromSite, Sun Pharmaceuticals), from the days of finally having an ester topical steroid (Lotemax suspension, Bausch + Lomb) to now having submicron- and nano-formulations of the same with greater aqueous penetration (Lotemax SM, Bausch + Lomb; Inveltys, Kala), from the days of hourly topical steroid prednisolone dosing to now having emulsion formulations (Durezol, Novartis) with greater potency and lower dosing.
The problem with even these newer formulations and evolutions in topical eye drop therapy is still cost to patients, inconvenience, reliance on patient compliance and patient ability to instill them properly, unwanted ocular side effects and ocular surface toxicity problems. In a personal evaluation of 54 cataract surgery patients, nearly 93% of patients demonstrated improper eye drop administration techniques as observed when recorded on video. Some of these self-administration issues identified in the study included 31.5% missing their eye, 57.4% contaminating the bottle tip, 31.5% instilling an incorrect number of drops and 77.8% failing to wash their hands before drop instillation. Difficulties with eye drop administration may result in trauma to the ocular surface, predisposition to infection from contaminated bottle tips and ultimately poor visual outcomes. Solutions to the eye drop problem we frequently encounter with our cataract patients include fewer drops with compounded formulations, preservative-free drops, transzonular/intravitreal injections (Tri-Moxi, Imprimis), intracameral medications (Omidria, Omeros; Dexycu, EyePoint Pharmaceuticals; antibiotics) and intracanalicular medication (Dextenza, Ocular Therapeutix).
Intravitreal steroid/antibiotic compounded combinations such at Tri-Moxi and Pred-Gati (Imprimis) can be injected by a transzonular or pars plana approach. The former has risk for iris/vitreous prolapse, damage to zonules and/or poor visualization for positioning of a premium IOL. The latter has a higher risk for increased IOP, peripheral retinal tear, subretinal/suprachoroidal injection and/or accidental ciliary body trauma with resultant vitreous hemorrhage, but it has better visualization than the transzonular approach.
Intracameral medications include antibiotics such as moxifloxacin (compounded alone or with dexamethasone, or from Vigamox [Alcon] bottle directly) and cefuroxime (compounded). There is a current American Society of Cataract and Refractive Surgery prospective randomized clinical trial with intracameral moxifloxacin ongoing. Dexycu (dexamethasone intraocular suspension 9%) is the first and only FDA-approved single dose 0.005 mL intracameral steroid for the treatment of postoperative inflammation. Dexycu is Verisome technology based on acetyl triethyl citrate organic material widely used as a flavoring agent. Verisome is biocompatible and biodegradable and delivers a relatively high initial dose that decreases over time, resulting in a sustained clinical effect for up to 30 days in most patients, as seen in the FDA trials. The 0.005 mL 2-mm spherule is delivered under the iris at the end of the cataract procedure, and more advanced holding techniques include an anterior subcapsular technique sandwiching the sphere between the edge of the IOL optic under the iris and the anterior capsular edge in the same vicinity. Anterior chamber clearing at postoperative day 8 in cataract surgery as a primary endpoint in the Dexycu FDA trial had three times more complete anterior chamber clearing than placebo. With Dexycu, complete anterior chamber clearing started as early as day 1 postoperatively and continued through day 30 in the clinical trial.
One of my personal pearl techniques for successful delivery of Dexycu is using the paracentesis and not the main incision. Make sure the main incision is hydrated and sealed completely. Instill intracameral antibiotic if used first and Dexycu last, and fill the eye to slightly higher IOP than desired just before delivering Dexycu. Fill a 1 cc syringe with 0.3 cc of Dexycu, and use either the 25-gauge cannula with the kit or smaller 27 gauge and make sure the Dexycu is at the end of the cannula and primed with no bubbles. Wipe the tip of the cannula free from Dexycu residue before instilling it into the anterior chamber. Use the subcapsular technique above, and you can wash out the Dexycu and reinstill if needed.
Omidria (phenylephrine and ketorolac intraocular solution 1%/3%) is the first and only NSAID-containing product approved by the FDA for intraocular use to maintain pupil size by preventing intraoperative miosis and reducing postoperative ocular pain. Advantages of this formulation over compounded “Shugarcaine” is that Omidria is preservative- and bisulfite-free, which increases the risk for toxic anterior segment syndrome postoperatively. Real-world evidence through peer-reviewed publications after FDA approval has shown that Omidria prevents intraoperative floppy iris syndrome, prevents iris prolapse, reduces cystoid macular edema, decreases breakthrough iritis, shortens surgical times, decreases the use of pupil-expansion devices when compared with epinephrine intracameral use, reduces the need for perioperative opioids such as fentanyl during surgery while decreasing visual analog scale pain scores, prevents miosis during femtosecond laser-assisted surgery, and improves uncorrected visual acuity on the day after cataract surgery.
Dextenza (dexamethasone 0.4 mg intracanalicular insert) is an FDA-approved steroid placed intracanalicularly for the treatment of ocular inflammation and pain after ophthalmic surgery and, like Dexycu, will last up to 30 days. My Dextenza “5 D” approach is to drag the lower lid temporally, dry the puncta area with the broad side of a Weck-Cel sponge, dilate the punctum with intermittent pauses to make the sphincter relax, direct the insert horizontally to bypass the initial 2 mm turn into the canaliculus, and don’t be dumb and know the lid/canalicular anatomy well. I also dry the lid skin with 4 × 4 dry gauze and remove my gloves at the end of the procedure to make it easier to drag the eyelid temporally.
The good news is Omidria, Dextenza and Dexycu all have J-codes and are reimbursable at the facility level via the pass-through system made available by CMS. In summary, these alternative drug delivery options are all FDA approved and help alleviate the issue of patient compliance and improve ocular surface toxicity, outcomes and patient experience with our premium surgery. Remember, less is more.
- References:
- Acetyl triethyl citrate. The Human Metabolome Database. www.hmdb.ca.
- Bucci FA Jr, et al. Clin Ophthalmol. 2017;doi:10.2147/OPTH.S132552.
- Donnenfeld ED, et al. Clin Ophthalmol. 2019;doi:10.2147/OPTH.S229515.
- Silverstein SM, et al. J Cataract Refract Surg. 2018;
- doi:10.1016/j.jcrs.2018.05.029.
- Visco D. Clin Ophthalmol. 2018;doi:10.2147/OPTH.S149522.
- Walter K, et al. J Cataract Refract Surg. 2019;doi:10.1016/j.jcrs.2018.11.004.
- For more information:
- Mitchell A. Jackson, MD, can be reached at Jacksoneye, 300 N. Milwaukee Ave., Suite L, Lake Villa, IL 60046; email: mjlaserdoc@msn.com.
Disclosure: Jackson reports he is a consultant for Ocular Therapeutix, Eyepoint Pharmaceuticals, Omeros, Bausch + Lomb, Novartis, Kala Pharmaceuticals, Sun Pharmaceuticals and Imprimis.
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