CEDARS/ASPENS Debates

Troubleshooting the initiation of cyclosporine for dry eye

Jonathan D. Solomon, MD, and Cynthia A. Matossian, MD, FACS, discuss strategies to ease the introduction of cyclosporine.

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.

Dry eye disease is one of the most frequently seen problems in the eye care professional’s office. Cyclosporine drops have become the mainstay of treatment of this condition. Some physicians have noted difficulty with the initiation of cyclosporine due to the delay in onset and the subjective irritation some patients note upon instillation. This month, Jonathan D. Solomon, MD, and Cynthia A. Matossian, MD, FACS, discuss their strategies to initiate cyclosporine with their patients. We hope you enjoy this discussion.

Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor

Alternatives to steroids, NSAIDs emerging

Jonathan D. Solomon

The number of patients who present to my office with ocular surface-related symptoms is staggering. A significant subset will be diagnosed with aqueous tear deficiency and/or would benefit from topical immunomodulation. As a matter of disclosure, I am compelled to admit that the overwhelming majority of my patients are granted a topical steroid when asked to institute Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan). It is my belief that we see less burning and irritation when a steroid or NSAID is applied before the topical cyclosporine, with the hopes of improving compliance in the critical induction period. However, Restasis is currently the only FDA-approved treatment option in what has become a multibillion dollar industry.

As eye care providers, our goal is to achieve and maintain quality vision without compromising quality of life. With this in mind, we are often faced with the harsh reality of assisting our patients, or clients, with the difficult decision as to where to make their investments regarding treatment options. I realize this is a dirty subject, but it is one that is particularly relevant at this time of year — when deductibles have not been met. In my part of the country, it is not uncommon to have patients call in to complain about the cost of Restasis. But my staff is well versed and prepared to direct new users to mytearsmyrewards.com, a site that can save patients hundreds of dollars. It provides access to the Restasis Patient Support Center along with other minor, but real, benefits, such as free supplemental samples of Refresh lubricant eye drops (Allergan). But there is no easy answer when the call comes in regarding topical NSAIDs or generic steroid drops that will break the monthly budget. And sadly, as I have heard this a lot over the past few months, it becomes a real chore to explain the “donut hole” or to simply agree that the cost of generic drugs has skyrocketed.

But there are a number of ways in which we can achieve the goal of improving the ocular surface environment when instituting Restasis, without the financial burden of concomitant steroids or NSAIDs. When you look at the actual data, the percentage of patients who describe burning upon instillation was slightly more than double when compared with a topical lubricant and only accounted for 15% of respondents, and there was no suggestion as to the intensity or duration of irritation. So when speaking to my patients before institution of Restasis treatment, I advise them that there may be some burning or irritation and that it often is temporary, and then I end with the analogy that it is like water on an open wound. More often than not, this is enough coaching to achieve adequate compliance during the critical first few months. Perhaps a little more hand-holding is required in lieu of the topical steroid/NSAID. And this is not a sprint. Protracted therapy is often required, and there is no substitute for good communication.

I will concede that supplemental topical anti-inflammatories anecdotally achieve better outcomes during the Restasis-induction period and are a widely held preference. Yet with emerging therapeutic strategies that include naturally occurring anti-inflammatory omega-3 fatty acids; mechanical techniques that improve tear quality; as well as the potential for devices, such as those that stimulate tears, options are now available that reduce the risk profile below that of a topical steroid and are proving to be reasonable steroid-sparing alternatives. Furthermore, as the insurance coverage landscape continues to change, we as clinicians will have to remain cognizant of the potential burdens on our patients and adapt to the foreseeable shortcomings. We are obliged to be creative in our efforts to meet the needs of our patients when necessary.

Disclosure: Solomon reports he is a consultant to Allergan.

Steroid may help patients achieve comfort faster

Cynthia A. Matossian

Dry eye affects approximately 25 million Americans; adult women are twice as likely to have this disease compared with men. Armed with the results from a variety of diagnostic tests, the patient’s history and symptomology, I make the diagnosis of dry eye after the slit lamp examination using both fluorescein and lissamine green dyes. I start patients on re-esterified oral omega-3 supplements, a microwaveable hot mask (Bruder) and Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan). Some patients experience burning and stinging with cyclosporine drop instillation and use this reported side effect as a reason to quickly discontinue the medication before experiencing its benefits.

As ophthalmologists, we want to improve the ocular surface condition of our patients as soon as possible while minimizing the discomfort they experience with the prescribed treatment regimen. With that goal in mind, I often pair a short course of steroids and/or NSAIDs along with Restasis to help “jump start” the anti-inflammatory therapy and to alleviate the initial complaints of burning.

In my investigator-initiated study, I wanted to determine whether adding either a steroid or an NSAID would result in better patient compliance in those prescribed Restasis compared with patients who were prescribed Restasis alone.

We enrolled 50 patients in this study: Restasis alone (group 1, 18 patients), Restasis plus Lotemax gel drops (loteprednol, Bausch + Lomb; group 2, 13 patients) and Restasis plus Bromday/Prolensa (bromfenac, Bausch + Lomb; group 3, 19 patients). All patients were instructed to instill Restasis twice daily; group 2 instilled the steroid drops 15 minutes before each Restasis instillation for the first 2 weeks and then discontinued steroid use. Group 3 instilled the NSAID 15 minutes before each Restasis drop for 2 weeks and then discontinued its use.

The patients underwent four visits (initial visit and at months 1, 3 and 6 after the initial visit date). All subjects underwent tear osmolarity testing and lissamine green staining at each visit. In addition, the patients were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire at baseline and again at the last visit.

The data analysis demonstrated that there were no statistically significant differences in any of the parameters tested, but there were distinct clinical nuances. The OSDI score in group 1 did not show much improvement from baseline, meaning those patients did not believe their symptoms were better at the 6-month final visit than at baseline. It is possible that the discomfort associated with the instillation negatively affected the perceived symptoms as measured on the OSDI. It is also possible that due to the burning, some patients were less complaint with the twice-daily dosing regimen. Group 2 had the greatest improvement in scores (–7.08), and group 3 also had an improvement in OSDI scores (–4.77) at the final visit compared with the baseline evaluation. This suggests that adding either a steroid or an NSAID to Restasis improves the patient-perceived symptoms and/or the level of discomfort associated with the drop instillation. This, in turn, will hopefully translate into better compliance with the prescribed treatment course due to increased overall ocular comfort.

My patients reported better outcomes when I prescribed concomitant steroid therapy with Restasis than if an NSAID or nothing was added to their Restasis induction. I believe the addition of a short course of loteprednol etabonate ophthalmic suspension as adjunctive therapy at the time of Restasis initiation may benefit patients during the cyclosporine dose-loading period.

Disclosure: Matossian reports she is a consultant to Allergan and Bausch + Lomb.

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.

Dry eye disease is one of the most frequently seen problems in the eye care professional’s office. Cyclosporine drops have become the mainstay of treatment of this condition. Some physicians have noted difficulty with the initiation of cyclosporine due to the delay in onset and the subjective irritation some patients note upon instillation. This month, Jonathan D. Solomon, MD, and Cynthia A. Matossian, MD, FACS, discuss their strategies to initiate cyclosporine with their patients. We hope you enjoy this discussion.

Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor

Alternatives to steroids, NSAIDs emerging

Jonathan D. Solomon

The number of patients who present to my office with ocular surface-related symptoms is staggering. A significant subset will be diagnosed with aqueous tear deficiency and/or would benefit from topical immunomodulation. As a matter of disclosure, I am compelled to admit that the overwhelming majority of my patients are granted a topical steroid when asked to institute Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan). It is my belief that we see less burning and irritation when a steroid or NSAID is applied before the topical cyclosporine, with the hopes of improving compliance in the critical induction period. However, Restasis is currently the only FDA-approved treatment option in what has become a multibillion dollar industry.

As eye care providers, our goal is to achieve and maintain quality vision without compromising quality of life. With this in mind, we are often faced with the harsh reality of assisting our patients, or clients, with the difficult decision as to where to make their investments regarding treatment options. I realize this is a dirty subject, but it is one that is particularly relevant at this time of year — when deductibles have not been met. In my part of the country, it is not uncommon to have patients call in to complain about the cost of Restasis. But my staff is well versed and prepared to direct new users to mytearsmyrewards.com, a site that can save patients hundreds of dollars. It provides access to the Restasis Patient Support Center along with other minor, but real, benefits, such as free supplemental samples of Refresh lubricant eye drops (Allergan). But there is no easy answer when the call comes in regarding topical NSAIDs or generic steroid drops that will break the monthly budget. And sadly, as I have heard this a lot over the past few months, it becomes a real chore to explain the “donut hole” or to simply agree that the cost of generic drugs has skyrocketed.

But there are a number of ways in which we can achieve the goal of improving the ocular surface environment when instituting Restasis, without the financial burden of concomitant steroids or NSAIDs. When you look at the actual data, the percentage of patients who describe burning upon instillation was slightly more than double when compared with a topical lubricant and only accounted for 15% of respondents, and there was no suggestion as to the intensity or duration of irritation. So when speaking to my patients before institution of Restasis treatment, I advise them that there may be some burning or irritation and that it often is temporary, and then I end with the analogy that it is like water on an open wound. More often than not, this is enough coaching to achieve adequate compliance during the critical first few months. Perhaps a little more hand-holding is required in lieu of the topical steroid/NSAID. And this is not a sprint. Protracted therapy is often required, and there is no substitute for good communication.

PAGE BREAK

I will concede that supplemental topical anti-inflammatories anecdotally achieve better outcomes during the Restasis-induction period and are a widely held preference. Yet with emerging therapeutic strategies that include naturally occurring anti-inflammatory omega-3 fatty acids; mechanical techniques that improve tear quality; as well as the potential for devices, such as those that stimulate tears, options are now available that reduce the risk profile below that of a topical steroid and are proving to be reasonable steroid-sparing alternatives. Furthermore, as the insurance coverage landscape continues to change, we as clinicians will have to remain cognizant of the potential burdens on our patients and adapt to the foreseeable shortcomings. We are obliged to be creative in our efforts to meet the needs of our patients when necessary.

Disclosure: Solomon reports he is a consultant to Allergan.

Steroid may help patients achieve comfort faster

Cynthia A. Matossian

Dry eye affects approximately 25 million Americans; adult women are twice as likely to have this disease compared with men. Armed with the results from a variety of diagnostic tests, the patient’s history and symptomology, I make the diagnosis of dry eye after the slit lamp examination using both fluorescein and lissamine green dyes. I start patients on re-esterified oral omega-3 supplements, a microwaveable hot mask (Bruder) and Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan). Some patients experience burning and stinging with cyclosporine drop instillation and use this reported side effect as a reason to quickly discontinue the medication before experiencing its benefits.

As ophthalmologists, we want to improve the ocular surface condition of our patients as soon as possible while minimizing the discomfort they experience with the prescribed treatment regimen. With that goal in mind, I often pair a short course of steroids and/or NSAIDs along with Restasis to help “jump start” the anti-inflammatory therapy and to alleviate the initial complaints of burning.

In my investigator-initiated study, I wanted to determine whether adding either a steroid or an NSAID would result in better patient compliance in those prescribed Restasis compared with patients who were prescribed Restasis alone.

We enrolled 50 patients in this study: Restasis alone (group 1, 18 patients), Restasis plus Lotemax gel drops (loteprednol, Bausch + Lomb; group 2, 13 patients) and Restasis plus Bromday/Prolensa (bromfenac, Bausch + Lomb; group 3, 19 patients). All patients were instructed to instill Restasis twice daily; group 2 instilled the steroid drops 15 minutes before each Restasis instillation for the first 2 weeks and then discontinued steroid use. Group 3 instilled the NSAID 15 minutes before each Restasis drop for 2 weeks and then discontinued its use.

PAGE BREAK

The patients underwent four visits (initial visit and at months 1, 3 and 6 after the initial visit date). All subjects underwent tear osmolarity testing and lissamine green staining at each visit. In addition, the patients were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire at baseline and again at the last visit.

The data analysis demonstrated that there were no statistically significant differences in any of the parameters tested, but there were distinct clinical nuances. The OSDI score in group 1 did not show much improvement from baseline, meaning those patients did not believe their symptoms were better at the 6-month final visit than at baseline. It is possible that the discomfort associated with the instillation negatively affected the perceived symptoms as measured on the OSDI. It is also possible that due to the burning, some patients were less complaint with the twice-daily dosing regimen. Group 2 had the greatest improvement in scores (–7.08), and group 3 also had an improvement in OSDI scores (–4.77) at the final visit compared with the baseline evaluation. This suggests that adding either a steroid or an NSAID to Restasis improves the patient-perceived symptoms and/or the level of discomfort associated with the drop instillation. This, in turn, will hopefully translate into better compliance with the prescribed treatment course due to increased overall ocular comfort.

My patients reported better outcomes when I prescribed concomitant steroid therapy with Restasis than if an NSAID or nothing was added to their Restasis induction. I believe the addition of a short course of loteprednol etabonate ophthalmic suspension as adjunctive therapy at the time of Restasis initiation may benefit patients during the cyclosporine dose-loading period.

Disclosure: Matossian reports she is a consultant to Allergan and Bausch + Lomb.