Disclosures: Singh reports financial connections with Alcon, Allergan, Bausch + Lomb, EyePoint, Kala, Novartis and Ocular Therapeutix.
March 18, 2020
6 min read

Newer brands, compounded drugs improve efficacy, compliance

Complex postoperative medication regimens may be difficult and costly for many patients.

Disclosures: Singh reports financial connections with Alcon, Allergan, Bausch + Lomb, EyePoint, Kala, Novartis and Ocular Therapeutix.
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Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a joint society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.

The use of compounded ophthalmic medications has long been a controversial topic. While the use of these products may give patients access to medications that they would not otherwise have, whether it is due to availability or affordability, they also come with certain risks.

This month, Gary Wörtz, MD, and Inder Paul Singh, MD, discuss their thoughts on the concept of using compounded ophthalmic medications. We hope you enjoy the discussion.

Kenneth A. Beckman, MD, FACS

Compounded drops save time, money

Gary Wörtz, MD
Gary Wörtz

In my opinion, compounded drops are the closest thing we have seen to the holy grail of postop pharmaceuticals in my career. Not only do compounded drops save patients money, the quality and convenience compared with both brand-name and generic formulations have piqued the interest of both providers and patients.

Previously, we had an unmet need in eye care, in which medicines continued to become more expensive with only incremental improvements. Among new formulations of steroids, antibiotics and NSAIDs, the only advantage seen was reduced dosage from four times a day down to once or twice a day.

With the increasing prices, however, one of the biggest challenges in preparing a patient for cataract surgery was trying to get them their eye drops. I have patients who were spending hundreds and hundreds of dollars, almost as much as they were spending on the surgery. It became a full-time job for a staff member to try to get these eye drops prescribed, dispensed and filled.

On top of that was the complexity of schedule: multiple drops taken daily with a tapering schedule over weeks among patients who are often elderly and may have more difficulty with compliance. Understanding the nuances of shaking a bottle and matching the bottle with the instruction schedule were often too cumbersome. Despite efforts to provide printout sheets that a patient could mark and lots of education, phone calls and staff time, we still routinely saw patients who could not manage their schedule and would be inadvertently noncompliant with their drop regimen.

Then, about 5 years ago, I was introduced to the intriguing concept of compounded drops by my friend and colleague Bill Wiley, MD. I started using them shortly thereafter and have had great success ever since. I currently use the combination prednisolone acetate, gatifloxacin and bromfenac (Ocular Science). In more than 5,000 consecutive cases, I have had no increase in macular edema, no noticeable increase in inflammation rates and zero endophthalmitis.


Additionally, there are various companies with multiple formulations. There are compounded drops that combine steroid, antibiotic and NSAID along with some for patients who only need a steroid and antibiotic. Some companies are also developing formulations for glaucoma and myopia prevention.

Switching to compound drops has probably been the single most beneficial change I have had to my ophthalmic practice in the 11 years since I finished training. It has improved the quality of my life, my staff’s quality of life and my patients’ quality of life. The price for compounded drops is always lower than any branded drug and almost always less than paying three copays. It is a rare situation that we can save time and cost while simplifying the process for our patients and staff.

By taking medications that are complicated to acquire with a complex schedule and reducing that complexity down to a drop that we can dispense in our office, we can make sure that the patient has exactly what they need before they go home after surgery. It takes this three-headed monster that has been expensive to both patients and our practice in time and staff hours and turns it into a simple process with one bottle.

Disclosure: Wörtz is a member of the medical advisory board for Ocular Science.

Educated patients may choose branded drugs

Inder Paul Singh, MD
Inder Paul Singh

One point that may be overlooked in the conversation about eye drops is the formulation and, more specifically, the inactive ingredients. For many years, we have known that the effectiveness, tolerability and bioavailability of the medications are based upon the inactive ingredients. Most of any drug in a bottle is made up of these excipients.

Looking at specific brand examples, we have the glaucoma medication Alphagan (brimonidine, Allergan) that had a higher concentration of the active ingredient originally and then was re-released as Alphagan P with an active concentration of 0.1%. The company did not change the active molecule; it changed the pH of the solution by changing the preservative. By doing this, it improved the stability of brimonidine without disrupting the efficacy of the active ingredient. This is the power of the vehicle. The same can be said for the NSAID Prolensa (bromfenac 0.07%, Bausch + Lomb). The concentration of the medication was decreased with no loss of efficacy by reducing the pH to help increase bioavailability. For Lotemax SM (loteprednol 0.38%, Bausch + Lomb), the loteprednol particle size was decreased to allow better absorption, allowing for a decreased concentration from 0.05% of active medication with no loss of efficacy.


The preservative and other inactive ingredients are not the only factors that can affect the efficacy of an eye drop medication, especially when we turn our attention to generic formulations. Because the FDA has no true oversight on where companies obtain inactive ingredients, even the bottle-make itself, these chemical makeups can affect the medication.

Dosing regimen is another factor that can affect patient acceptance and tolerability. A study conducted by John A. Hovanesian, MD, FACS, and Edward J. Holland, MD, found that patients treated with branded nepafenac 0.3% had significantly better objective and subjective outcomes after cataract surgery than patients treated with generic ketorolac 0.5%. Burning and stinging lasted longer in the ketorolac group, while blurry, hazy or foggy vision, as well as a film or coating on the eye, lasted longer in the nepafenac group (P < .0001).

All objective measures were statistically significantly greater for ketorolac 0.5% vs. nepafenac 0.3% as follows: corneal staining (64% vs. 28%), Oxford grade 2 or greater staining (28% vs. 4%), Schulze grade 30 or greater conjunctival erythema (65% vs. 36%) and abnormal tear breakup time greater than 10 seconds (77% vs. 51%) (all P < .0001).

In some cases, the active ingredient of an eye drop could get stuck to the side of the bottle. A special chemical treatment was needed to make sure the molecules remained suspended or else a patient may not receive the right dose between this problem of becoming stuck to the bottle or issues with settling. For these and other reasons, I prefer not to use generic medications around ocular surgery and instead focus on brand names if possible. I want to maintain control over not just the intraoperative period but the postop healing period as well. Additionally, patients who are educated on the value of brand-name medications may be willing to pay more for them to a certain degree.

We conducted an in-office study involving 20 patients who had opted for a generic glaucoma medication. When they came back in, we gave them a sheet of paper that briefly explained the differences in brand-name and generic medications. Of the 13 patients who opted for the brand name, the average difference in cost was $38. For those who chose to stay on the generic, the average difference in cost was $86. Therefore, a patient is oftentimes willing to pay more for a medication or service as long as they understand the value proposition.


So then, because compounding medications are not exactly “generic,” where do they fit in? Compounding pharmacies fill a void for patients who cannot tolerate or afford the typical postop drop regimen, which often includes three or four brand-name or generic varieties of eye drop medication. Compounding pharmacies offer combinations of these medications that are not even available as generic or brand-name combinations. I do appreciate that the cost is often lower with these compounded medications compared with the total cost of the generic or branded regimens. Compliance no doubt improves by using one bottle, and patient satisfaction does often increase as well. Unlike a generic medication, where there could be many companies manufacturing the drop, we see consistency with the bottle and inactive ingredients in compounded drops, and one can obtain potency data that may be more difficult to track with generic options.

There is actually more science behind these compounded drops than some might be aware of. For instance, the vehicle for the compounded glaucoma drops and cataract drops by one of the largest pharmacies contains a surfactant that allows the individual molecules to remain equally distributed. Another factor to consider when choosing a compounding pharmacy is its quality and regulations, often inspected by the FDA.

Our job as surgeons is to be educators. Whether it is premium lenses or a drug, whether it is brand name or not, it is education first. Arming patients with enough knowledge to make an informed decision is the philosophical change we have seen in the last decade in glaucoma and cataract care. It is crucial that we do not assume a patient cannot afford a certain medication or is unwilling to pay for a better or more consistent formulation.

We are pushing toward improved compliance and high patient satisfaction while maintaining a healthy ocular surface, often achieved by decreasing the number of drops in the eye. Whether brand-name or compounding drops, we need to individualize the treatment utilizing all the tools we have with those previously mentioned goals in mind.

Disclosure: Singh reports financial connections with Alcon, Allergan, Bausch + Lomb, EyePoint, Kala, Novartis and Ocular Therapeutix.