Pharmaceutical Manufacturers Alter Sampling Policies

For fear of potential fines from the FDA, pharmaceutical manufacturers are altering—and in some cases stopping— the sampling of certain antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) to ophthalmic centers and physicians’ offices.

Alcon Laboratories, Inc., recently changed its call-and-sampling procedure for Vigamox (moxifloxacin 0.5%), a fluoroquinolone indicated for the treatment of conjunctivitis but commonly used off label in cataract surgery for the prevention of endophthalmitis. Allergan, Inc., has hired a third-party organization to provide samples of Zymaxid (gatifloxacin 0.5%), a fluoroquinolone, and Acuvail (ketorolac 0.45%), an NSAID routinely used off label for the prophylaxis of cystoid macular edema.

Alcon would not comment on why or how it is altering its sampling procedures related to Vigamox, but Allergan attributed its change in policy to an issue of capacity. “It’s due to the prioritization of Allergan’s eye care sales force against the successful launch of Lumigan 0.01% and Lastacaft, which were recently approved by [the] FDA, and the continued growth of Restasis,” Allergan spokeswoman Crystal Muilenburg said in an interview with CRSToday. “If a physician requests a sample for Zymaxid or Acuvail, instead of the sales force providing them directly, it could be shipped out by a third party.”

All of this leaves drug manufacturers in a difficult position, as they try to build sales of their newer, more expensive drugs without appearing to market products for off-label uses. In addition to sampling, the changes could also affect the way pharmaceutical companies advertise and alter the dialogue between sales representatives and physicians, who often rely on the former for important information about these agents.

Some physicians believe changing marketing practices could also stifle innovation, because there will be less incentive for drug companies to develop new therapeutic agents if they cannot be used for surgical indications. The crackdown on marketing practices also leaves physicians who rely on samples of fluoroquinolones and nonsteroidal antiinflammatory drugs with some potentially difficult decisions. Many surgeons are now re-evaluating their choice of antibiotic, and some have vowed to move to generic formulations and older generations of drugs. These switches, though, could expose physicians to another unwanted consequence: medical malpractice.

—Stephen Daily, news editor

ERIC D. DONNENFELD, MD

The FDA’s recent decision to crack down on the off-label marketing of pharmaceuticals has resulted in fines totaling more than $3 billion being levied on drug makers.¹ One aspect of the fallout from the FDA’s actions is that ophthalmic manufacturers will only sample medications in direct relation to the agent’s use in terms of the approved indication. This has prompted both Allergan, Inc., and Alcon Laboratories, Inc., to dramatically reduce their sampling of Zymaxid and Vigamox. Both of these drugs are FDA approved for the treatment of conjunctivitis but not for surgical prophylaxis, for which they are most commonly used.

Allergan attempted to challenge the FDA’s crackdown on off-label marketing by suing the agency in federal court. Allergan stated that denying the Botox off-label discussion, which was well documented in the medical literature, was a violation of freedom of speech. As part of its $600 million settlement with the FDA, Allergan agreed to withdraw the lawsuit.² Perhaps coincidentally, once Allergan dropped its lawsuit, the FDA suddenly approved several of the company’s new products.

The FDA’s crackdown is another example of how the agency has exceeded its role of protecting Americans: this has nothing to do with protection. The FDA has made it almost impossible for exciting new drugs to be approved in the United States. Instead, pharmaceutical makers are fleeing abroad, where it is easier, faster, and less expensive to undertake clinical studies. Diquafasol (codevelopers Santen Inc. and Inspire Pharmaceuticals, Inc.), a promising treatment for dry eye, was rejected here but recently approved in Japan. To my knowledge, this is the first time an American ophthalmic pharmaceutical gained approval abroad and not here at home. It has been estimated that the cost of approving a new drug in the United States is over $100 million.³

Economically speaking, the United States has been a country that imports significantly more than it exports, resulting in a negative trade balance. Health care has been one of the lone bright spots, but I predict this will not last much longer.

Furthermore, the reduction in sampling will require patients either to pay more for ophthalmic medications or to move toward generic agents. Generic medications, however, are often previous-generation pharmaceuticals that are not prepared in the same way as the premium, brand-name products. These generics can sometimes have deleterious effects on outcomes. Some patients will benefit from the decreased cost but at the expense of an increased risk for a suboptimal outcome.

Most important, I have a real concern about the future of medical care in the United States. A topical antibiotic cannot be marketed for antibiotic prophylaxis for cataract surgery until a study is performed. Performing such a study is impossible because it would be unethical to have a control group not receive an antibiotic. There is simply no reason for ophthalmic pharmaceutical companies to develop new antibiotics. As microbial resistance develops to our current treatment options, we may not have new choices in the very near future because of the decisions being made by today’s FDA.

STEPHEN G. SLADE, MD

The halting of surgical samples has important ramifications for surgeons and patients. At my practice, we were using samples for our indigent patients, because the drops cost hundreds of dollars. In some cases, their cost approaches that of the patient’s surgery. Our office surveyed the local pharmacies to determine pricing, and even I was amazed at how expensive these medications are. Now, we have few samples, which we save for the patients who really need them. We will also purchase some drops ourselves, which is costly for the practice.

When I prescribe an antibiotic, I should make that decision based on efficacy and less on cost. I do not want to tell patients what is best and then figure out what they— or I—can afford. The patients have certainly noticed what is happening. We have many with insurance plans that do not cover the latest agents, only older antibiotics. It is tough when patients call and ask, “What should I do? My insurance company only covers an older drug.”

This is a microcosm of what is happening in health care in general. In this country, we have the ability to provide ultimate care, but we cannot afford to give it to all those who need it. How do we manage this? It is a type of rationing, it is real, and at some point, it will be more prevalent.

I am also disturbed that concerns regarding off-label marketing have led to the halting of samples. I have no problem with a drug representative’s telling me what a pharmaceutical agent does, what its off-label uses are, and the experiences of other surgeons. I understand that he or she has a financial interest. Off label does not mean that the drug failed or is bad. It only means that it has not been submitted for approval or been approved by the FDA for that specific use. Most drugs and devices, due to simple economics, will never be submitted to FDA trials for every possible use. A huge percentage of what we do as ophthalmologists is off label. This is simply the practice of medicine. Anyone who is performing LASIK retreatments, doing wavefront-guided PRK, or prescribing antibiotics and steroids after surgery is doing so off label. The majority of the treatments in pediatric ophthalmology are off label, because the drugs were approved in adults.

Not allowing us access to this information is censorship. Let physicians, along with their patients, decide what is best for the patient based on all available information and experience. I believe that the people who are ultimately making these decisions do not understand what off label really means.

Everything cycles. This pendulum has swung too far. I hope that it starts to swing back.

STEVEN J. DELL, MD

I would like to take this opportunity to publicly address all of the various bacteria that reside in, or contaminate the eyes of, our patients. I hereby formally request that you cease evolving immediately. You see, this will be a necessary step on your part, because we humans will not be developing any new antibiotics for ophthalmic use in the foreseeable future. So, if you could just go ahead and not develop any new antimicrobial resistance capabilities, that would be great. Thank you for your cooperation.

Truly pivotal moments in health care are relatively rare. In the continuum of medical progress, it is difficult to pinpoint a specific event that changed everything. In ophthalmology, however, we have witnessed such an event. Our government, in its wisdom, has laid down the law, and the pharmaceutical industry has snapped to attention. The promotion of the off-label use of FDA-approved medication is radioactive territory and may result in hundreds of millions of dollars in fines as well as criminal charges. Recently, Allergan, Inc. was forced to pay $600 million to settle claims that it promoted Botox for unapproved uses such as headaches.²

Although physicians may prescribe drugs for off-label uses when appropriate, we all understand that it is illegal for pharmaceutical companies to promote these uses. A discussion about the propriety of this situation is beyond the scope of this article, but precisely how is “promotion” defined? Corporate sponsorship of educational symposia in which doctors state their own opinions now places these companies in an increasingly uncomfortable position. PowerPoint presentations must be scrubbed of any potentially damaging words, product identifiers, or deviations from approved statements. If clever physicians discover that an approved drug has enormous benefit for the treatment of a different condition, the manufacturer is obligated to pretend that the whole thing never happened. Absurdity.

The way that this is playing out in our little corner of the health care world is that the two largest ophthalmic pharmaceutical companies have concluded that the mere act of providing antibiotic samples and literature to ophthalmologists is a risk they can simply no longer afford to take. The government’s message to these companies is clear: most of these antibiotics are used off-label in a postoperative application, so stop promoting them now or face massive fines and criminal charges.

I wonder if the government officials who are responsible for this policy really understand what they have done. Do they imagine that public corporations will spend hundreds of millions of dollars to develop the next antibiotic so they can cheerfully promote it for the odd case of bacterial conjunctivitis? Obviously, they will not. In time, we may find ourselves reminiscing about the days when new antibiotics actually appeared on the market. For every 5,000 to 10,000 compounds that begin initial testing, only one drug reaches the market.4 The risk-versus-reward proposition, therefore, is already unfavorable for many drugs. If corporations’ discussion surrounding drugs is censored to conform to the strict criteria of the FDA’s approval, the incentive to invest in new compounds will vanish. This will play out in every sector of health care. Lifesaving advances in cardiology, cancer, or infectious disease will go unfunded, and new uses for old drugs will remain unexplored due to a lack of research funding.

What has happened in the past year or so? Drug development has pretty much come to a halt. The Obama administration has become so alarmed about this situation that it founded a federal research center to help create new medicines.⁵ So, the folks who brought us the US Postal Service and the Transportation Security Authority are getting into the drug development business. The newly minted National Center for Advancing Translational Sciences is charged with fostering new drugs, which will then, at some point, be handed off to the private sector. I am sure there are many instances in which governments were able to succeed in commercial enterprises where corporations have failed; I just cannot think of any right now.

WILLIAM B. TRATTLER, MD

I believe the FDA is unreasonable. First, doctors should be instructed on the optimal use of medications for patients—even if the dosing regimen or time frame differs from what the FDA approved. For example, most topical NSAIDs, such as bromfenac and Acuvail (Allergan, Inc.), are labeled to start 1 day prior to cataract surgery, and continue for only 14 days. Others are labeled to start the day after cataract surgery. However, there is research that suggests starting all NSAIDs 3 days preoperatively may have some advantages over the way these medications are labeled. In addition, research has found that extending the NSAID therapy to 1 month postoperatively may help reduce the risk of developing cystoid macular edema. Doctors should be provided with data from studies that look at the optimal use of FDA-approved medications beyond what the label states, and it is my opinion that company representatives should be allowed to share data from studies with physicians, because postapproval study results may help patients.

Another example includes certain drugs that are approved for preventing conjunctivitis. Surgeons have found that they are an important part of the prevention of postoperative infections—and are even considered standard of care. I believe this discussion should be allowed between doctors and the manufacturers.

The FDA should further adjust the way it reviews medications and allow for the approval of those agents used for infection prophylaxis and other conditions based on the available science. It is exceptionally expensive to attempt to conduct a trial that will prove a drug's efficacy regarding the prevention of infection, for example. If a pharmaceutical manufacturer can show that its antibiotic is safe and effective for killing infectious organisms, an allowance show be made for a type of approval that companies may discuss with doctors.

My biggest fear is that there will now be less incentive for companies to produce new therapeutic agents. What company is going to invest $20 million, $50 million, or $100 million in a new antibiotic that can only be approved and promoted for conjunctivitis? If the drug cannot be used or discussed in cataract surgery, where is the incentive for the drug company to develop a novel medication and get it approved?

JOHN F. DOANE, MD

The opportunity to make observations regarding the changing landscape of pharmaceutical sampling, FDA oversight, and companies’ being fearful of the off-label use of their products raises several interrelated issues.

About 6 months ago, I was involved in a discussion with other members of the ASCRS Cataract and Refractive Clinical Committees. The point of the discussion was the off-label use of approved devices or pharmaceuticals. To a physician, we came to the same conclusion that about 99% of what we do on a daily basis is off label. Our entire medical and surgical practices are essentially off label. How can this be? Two things come into play. The first key component is that the practice of medicine provides physicians with the opportunity and privilege to use their training, experience, and observational skills to treat diseases and, one hopes, cure patients. The situation is such because of the second component of the reality in which we practice: controlled scientific studies to prove or disprove the innumerable recommendations we make to patients on a daily basis have not or will not likely ever be completed. Possibly to the disdain of health policy wonks, clinical practice pattern-recommendation bureaucrats, controllers of health care remuneration, and plaintiff's attorneys, there simply is not the time or money to validate with a scientific study all that physicians do daily in their practices. To expect unequivocal scientific validation in a profession that is as much art as science will lead to disappointment.

This brings me to the relatively recent decision by pharmaceutical companies to discontinue samples of medications contained in postoperative surgical packs. The apparent reason for the change in samples’ availability is that physicians might be using them to care for patients postoperatively, when the medications may not have FDA approval for such use. I think we all agree that it is unacceptable for a company to market a device or medicine for an unapproved use. On the other hand, if a physician via his or her practice of medicine has figured out a useful application for a drug that benefits patients, it seems inherently ethical and moral to prescribe the most effective regimen for the patient.

My best example of this idea is from an occupational and rehabilitation specialist in Kansas City, Missouri. I was referred a patient that needed a combined cataract extraction and corneal endothelial transplantation. Unfortunately, the patient had marked head and neck tremor such that the only way I could have operated was to place her under general anesthesia. I had learned of a colleague’s off-label selective use of Botox injections to completely ameliorate tremors or spasticity. Suffice it to say, his ability to resolve my patient's problem and afford her the chance to have sight-correcting surgery without general anesthesia was miraculous from my perspective. Of interest, Allergan, Inc., was fined approximately $600 million for off-label promotions of Botox, and tens of millions of dollars were split between the five whistleblowers that worked for Allergan.² I wonder if any patients were hurt by the off-label use of Botox.

My hope is that reason will return to the FDA and the Federal Trade Commission. It seems that the present climate is painting all actors with the same wide brush. On the one hand, these agencies' actions are understandable (the legacy of Vioxx [Merck]), but on the other, it seems that we are witnessing the proverbial baby’s being thrown out with the bath water. Medical practice has allowed the discovery of innumerable applications that would otherwise never have been understood, let alone attempted. I hope for a return to a more rational appreciation of this history.

JOHN A. HOVANESIAN, MD

From a macroeconomic perspective, halting free samples of surgical pharmaceuticals may be a positive measure, because surgeons and patients should be choosing a drug based on its merit and relative cost. Previously, surgeons tended to group their prescriptions around one company that was particularly generous with samples, instead of choosing the best drug for each individual situation. Smaller drug makers—even those with superior drugs—would have difficulty competing with the larger companies. In some ways, this situation limits the patient’s access to the best drugs. The halting of drug sampling could level the playing field and allow market forces to dominate.

Microeconomically, however, halting sampling has a negative effect. The cost of health care is one of the biggest problems facing this country. One way to address the rising costs is on a case-by-case basis by providing free samples to patients who need them. This is a door that is now theoretically closed, and as a surgeon, I am sorry to see the broad-scale availability of samples go. The worry over liability prevents an act of kindness.

Following the $600 million fine levied last year against Allergan, Inc., for the off-label promotion of Botox, companies are increasingly listening to the advice of their lawyers.2 The alarming amount of regulation that is dictating the medical industry gets in the way of good patient care. I think we lose a lot more than we gain.

Certainly, there is a trend toward surgeons’ prescribing generic formulations more often. If the patient must absorb the cost, surgeons would like to prescribe the lowest-priced medication, which is a sound rationale. In my practice, where about 3,000 cataract cases are performed per year, we made the choice to use generics 1 year ago. Now, however, we are moving back to brand-name medications because we have seen an increase in cystoid macular edema with the use of generic ketorolac, prednisolone acetate, and ofloxacin. Thankfully, we did not see a higher rate of infection, but we certainly saw more inflammatory sequelae when we were using the nonbranded anti-inflammatory agents. We now use Bromday (bromfenac ophthalmic solution, 0.09%; Ista Pharmaceuticals, Inc.), Pred Forte (prednisolone acetate ophthalmic suspension, 1%; Allergan, Inc.), and Vigamox.

As surgeons, we need to do the responsible thing and recognize when generics are appropriate and when they are not, and we must let our patients know as well. At my practice, we are in the process of switching to a brand-name regimen. We give patients a choice and let them know what our recommendation is. We also inform them that, most of the time, patients do fine on generic medications, although that is not always the case. We tell patients, you have cataract surgery twice in your life; is this a chance you want to take? We also encourage our patients to shop around, as there is a wide variety in what pharmacies charge.

What seems to be an accepted truth is that generic agents cost less, and this is not always the case. In Medicare Part D, for example, when patients are in the “donut hole,” name-brand medications are discounted 75%. If a patient is prescribed a branded medication that costs $100, he or she will pay $25 and be credited with the full cost of the medication toward his or her deductible. A generic medication that costs $50 is only discounted 6% or 7%. This is an example of how the medication can cost twice as much, but the patient pays less in the donut hole. Patients are better off with branded medications in many cases, and this is not well understood.

RICHARD J. MACKOOL, MD

The major impact of the halting of surgical samples will be an increase in the costs of medical care both for patients and physicians. This action has been made necessary by regulations that prohibit the sampling of drugs that encourages their use for other-than-approved conditions; however, there is no conceivable benefit to anyone from the current situation. Certainly, patients are not protected from improper treatment. They will have to buy medications that they might otherwise have received at no charge, and surgeons who wish to reduce expenses for their patients will be forced to do so at their expense (ie, by purchasing the medications and providing them to their patients).

R. DOYLE STULTING, MD, PHD

The halting of sampling is based on drug manufacturers’ fear that they will be found not to be in compliance with regulations, because they are promoting off-label uses of drugs. In this regard, I believe it is inappropriate for the label to control medical care, the sharing of information, or the sampling of drugs. Ophthalmologists typically use drugs and devices off label on a daily basis. Off-label uses are described routinely in textbooks, and we would probably all be susceptible to malpractice suits if we did not prescribe off label.

There are many reasons why a particular indication for which a drug or device is effective may not be mentioned on the label. The manufacturer of that drug or device may have decided not to include patients with this indication in clinical trials because of cost or other issues. For example, almost all topical ocular antibiotics are evaluated and labeled for the treatment of conjunctivitis, because such patients are easy to recruit, tend to present a homogenous population, and provide an experimental population with which the FDA is familiar. Topical antibiotics are used routinely, however, for the treatment of corneal ulcers—a practice that is taught in medical school, is recommended in textbooks, and is the standard of care. If a patient presents with a corneal ulcer caused by an organism with unique susceptibility to an antibiotic that is not labeled for use with corneal ulcers, the practitioner had better prescribe that antibiotic, in spite of the fact that it is an off-label use.

A drug or device may be used off label because data become available to support its safety and efficacy after clinical trials were completed. Contraindications to the use of drugs or devices may also become apparent only after approval, so the converse of the typical “off-label argument” may be true: practitioners may sometimes not be providing optimal care if they follow the label.

Sampling provides practitioners with an opportunity to gain experience with new drugs. It also meets other needs for some patients, like providing drugs that are urgently needed for immediate treatment after normal business hours or for the treatment of indigent patients.

It is sad that the government has decided to interfere with medical practice by blocking communication between manufacturers and physicians. The government has implied and expressed condemnation of offlabel use and has taken steps that have caused manufacturers to discontinue sampling and stop sharing legitimate scientific information about off-label use. This interference will have a significantly detrimental effect on the services that physicians are able to provide, on their scientific knowledge, and on the health of US citizens.

Steven J. Dell, MD, is the director of refractive and corneal surgery for Texan Eye in Austin and chief medical editor of CRSToday’s sister publication Advanced Ocular Care. He is a consultant to Abbott Medical Optics Inc.; Alcon Laboratories, Inc.; Allergan, Inc.; and Bausch + Lomb. Dr. Dell may be reached at (512) 327-7000.

John F. Doane, MD, specializing in corneal and refractive surgery, is in private practice with Discover Vision Centers in Kansas City, Missouri, and he is a clinical assistant professor for the Department of Ophthalmology, Kansas University Medical Center. He is an investigator for Alcon Laboratories, Inc.; Bausch + Lomb; Calhoun Vision, Inc.; Carl Zeiss Meditec, Inc.; and ReVision Optics. Dr. Doane may be reached at (816) 478-1230; jdoane@discovervision.com.

Eric D. Donnenfeld, MD, is a clinical professor of ophthalmology at NYU and a trustee of Dartmouth Medical School in Hanover, New Hampshire. Dr. Donnenfeld is in private practice with Ophthalmic Consultants of Long Island in Rockville Centre, New York. He is a consultant to Abbott Medical Optics Inc.; Alcon Laboratories, Inc.; Bausch + Lomb; and Inspire Pharmaceuticals, Inc. Dr. Donnenfeld may be reached at (516) 766-2519; eddoph@aol.com.

John A. Hovanesian, MD, is in private practice at Harvard Eye Associates in Laguna Beach, California, and a clinical instructor at the UCLA Jules Stein Institute. He is a consultant to Allergan, Inc.; Inspire Pharmaceuticals, Inc.; Ista Pharmaceuticals, Inc; and Sirion Therapeutics. Dr. Hovanesian may be reached at (949) 951-2020; drhovanesian@harvardeye.com.

Richard J. Mackool, MD, is the director of The Mackool Eye Institute and Laser Center in Astoria, New York. He is a consultant to Alcon Laboratories, Inc. Dr. Mackool may be reached at (718) 728-3400, ext. 256; mackooleye@aol.com.

Stephen G. Slade, MD, is a surgeon at Slade and Baker Vision in Houston. He is a consultant to Abbott Medical Optics Inc.; Alcon Laboratories, Inc.; NuLens Ltd.; ReVision Optics, Inc.; and Technolas Perfect Vision GmbH. Dr. Slade may be reached at (713) 626- 5544; sgs@visiontexas.com.

R. Doyle Stulting, MD, PhD, is the director of the Stulting Research Center at the Woolfson Eye Institute in Atlanta. He has received consulting fees from Alcon Laboratories, Inc.; Allergan, Inc.; Bausch + Lomb; and Inspire Pharmaceuticals, Inc. Dr. Stulting may be reached at (770) 255-3330; dstulting@woolfsoneye.com.

William B. Trattler, MD, is the director of cornea at the Center for Excellence in Eye Care in Miami and the chief medical editor of Eyetube.net. He is also chief medical editor of CRSToday’s sister publication Advanced Ocular Care. He has received research funding from Alcon Laboratories, Inc.; Allergan, Inc.; Bausch + Lomb; EyeGate Pharma; Fera Pharmaceuticals; Inspire Pharmaceuticals, Inc.; Ista Pharmaceuticals, Inc.; LensAR Inc.; and QLT Inc. Dr. Trattler may be reached at (305) 598-2020; wtrattler@earthlink.net.

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Bromfenac Ophthalmic Solution 0.09%

Penetration and potency are now available in Bromday, a once-daily NSAID formulation.

BY UDAY DEVGAN, MD, FRCS(GLASG)
Modern cataract surgery is a safe, efficient, and minimally invasive procedure with the ability to restore excellent vision to our patients. The ultimate visual result is a combination of our surgical skill and the patient’s healing response. This is where nonsteroidal anti-inflammatory drugs (NSAIDs) are of benefit: to treat postoperative inflammation as well as address any pain after cataract surgery.

The choice of an NSAID after cataract surgery is important. Primary factors in the decision are the agent’s ability to provide the desired clinical benefits as well as convenient dosing to ensure patients’ compliance. Using a medication three or four times a day is a burden. Xibrom (bromfenac ophthalmic solution 0.09%; Ista Pharmaceuticals, Inc.) was the first NSAID on the market to be dosed twice a day. With a high degree of penetration and potency, Xibrom quickly became the market leader in ophthalmic NSAIDs, according to IMS Health Incorporated data from November 2010. Now, Ista Pharmaceuticals, Inc., has brought to market an NSAID with the strong clinical efficacy of Xibrom that is dosed just once per day: Bromday.

STUDIES

The Bromfenac Comparative trial was conducted to determine the optimal concentration for a once-daily formulation (data on file with Ista Pharmaceuticals, Inc.). Interestingly, the standard 0.09% concentration performed as well as a double-strength 0.18% concentration, indicating that the cyclooxygenase enzyme receptors were already saturated and blocked by the bromfenac molecule. Bromday’s high degree of penetration and potency can be attributed to the halogenation of the bromfenac molecule. With the added bromine moiety, the NSAID becomes highly lipophilic, which allows for rapidly achieved, sustained drug levels in the ocular tissues (Figure 1).

In the Bromday pivotal FDA trial, patients were evaluated for two endpoints. The primary efficacy endpoint was the summed ocular inflammation score on postoperative day 15. The secondary efficacy endpoint was patients’ reporting a pain score of “none” on postoperative day 1 (data on file with Ista Pharmaceuticals, Inc.). Importantly, in both the Bromday and placebo arms of this study, patients were not given a corticosteroid to control inflammation. All anti-inflammatory activity for the postoperative cataract patients was from Bromday alone (Figure 2).

For postoperative inflammation on day 15, the patients receiving Bromday had a summed ocular inflammation score level of just 1.1 compared with 2.8 for the patients assigned to placebo (P < .0001 for days 3, 8, 15, and 22). Patients were questioned about their pain level on postoperative day 1, after having received a total of three drops of Bromday. Slightly fewer than 95% of the treated patients reported “none” versus 70.5% for placebo (data on file with Ista Pharmaceuticals, Inc.).

Patients who had a lack of efficacy from the treatment were allowed to exit the trial as a measure of safety and comfort. Only 2.9% of the Bromday-assigned patients withdrew compared with 33% of those in the placebo group (Figure 3). These results show that Bromday given just once per day, as a sole anti-inflammatory agent, was clinically effective at reducing postoperative inflammation and pain (data on file with Ista Pharmaceuticals, Inc.).

CONCLUSION

Bromday is the first of a new generation of postoperative medications with convenient once-daily dosing. More importantly, it brings the same high level of penetration and potency seen previously in Xibrom with half the dosage, half the medication load, and half the benzalkonium chloride preservative.

While we keep up with the latest advances in surgical technique, biometry, and instrumentation, we should remember that what matters to each patient is his or her final visual outcome. To achieve excellence in this category, we must modulate the healing response by treating postoperative inflammation with a potent, safe, and efficacious NSAID like Bromday.

Uday Devgan, MD, FRCS(Glasg), is in private practice at Devgan Eye Surgery in Los Angeles. Dr. Devgan is the chief of ophthalmology at Olive View UCLA Medical Center, and he is an associate clinical professor at UCLA School of Medicine. He is a speaker for and/or consultant to Alcon Laboratories, Inc.; Allergan, Inc.; and Ista Pharmaceuticals, Inc.; but he stated that he has no direct financial interest in the products mentioned herein. Dr. Devgan may be reached at (800) 337-1969; uday@devganeye.com or devgan@gmail.com.

High-Concentration Moxifloxacin

Moxeza, a fourth-generation fluoroquinolone, delivers a high dosage of moxifloxacin to the ocular surface.

BY STEVEN M. SILVERSTEIN, MD
Moxeza (moxifloxacin 0.5%; Alcon Laboratories, Inc.) is a reformulation of the company’s Vigamox with a new vehicle, xanthan gum. The xanthan gum formulation allows the drug to stay on the eye longer and increases penetration into the ocular tissues. Moxeza can be delivered in high concentration to the tissues of the ocular surface.¹ This is beneficial when treating bacterial conjunctivitis or a bacterial infection of the cornea. In a randomized, double-masked, parallel group study, conjunctival concentrations of moxifloxacin were measured in 130 patients scheduled for phacoemulsification and implantation of an IOL. The patients were randomized to receive a one-drop instillation of Vigamox or Moxeza, and then conjunctival biopsies were obtained. The results showed that the conjunctival moxifloxacin concentration in patients treated with Moxeza was 1.8-fold higher than in patients treated with Vigamox (C_max = 43.8 μg/g for Moxeza achieved at 0.25 hours vs C_max = 24.1 μg/g at 0.5 hours for Vigamox). This demonstrates that Moxeza is able to penetrate the conjunctival tissues. Moxeza was also found to provide a larger total tissue exposure than Vigamox. These findings regarding tissue-penetration data are important because of the concentration-dependent nature of fluoroquinolones in the treatment of bacterial infections. This translates into a greater eradication of bacteria, which is important in the treatment of bacterial conjunctivitis.

DELIVERY SYSTEM

Most fourth-generation fluoroquinolones on the market share a similar coverage spectrum in terms of bacterial resistance and sensitivities. However, one of the advantages of Moxeza is the delivery system, which is designed to administer higher doses to the tissue. In a recent study, researchers compared the effectiveness of Moxeza to other fourth-generation fluoroquinolones in rabbit eyes with Staphylococcus aureus.² Eyes were topically treated with a single drop of 0.5% moxifloxacin, 0.3% gatifloxacin, or 0.5% gatifloxacin 60 minutes before the injection of 106 colony-forming units of Staphylococcus into the anterior chambers of these rabbit eyes. The eyes treated with Moxeza had significantly less bacteria than the untreated control and both concentrations of gatifloxacin. These results again demonstrate the ability of Moxeza to gain tissue penetration in order to reach the pathogens that are being targeted.

Having the opportunity to participate in the FDA trials that led to Moxeza’s appoval has provided me with great confidence in its broad-spectrum activity and better efficacy in eradicating the organisms most commonly associated with bacterial conjunctivits. These same bacteria are also the most frequently cultured from eyes suffering from postoperative endophthalmitis. Intuitively, therefore, the greater exposure time of the 0.5% formulation of Moxeza to the ocular surface and adnexa due to its xantham gum vehicle provides surgeons with the strongest possible protection currently available.

Steven M. Silverstein, MD, is the president of Silverstein Eye Centers in Kansas City, Missouri, and he is an assistant clinical professor of ophthalmology at the University of Missouri School of Medicine and the University Health Sciences, both in Kansas City. He is a consultant to Alcon Laboratories, Inc. Dr. Silverstein may be reached at (816) 358-3600; ssilverstein@silversteineyecenters.com.

The Advantages of Gatifloxacin 0.5%

Zymaxid’s higher concentration, preservation with BAK, speed to kill, and MICs enhance its efficacy.

BY JOHN R. WITTPENN JR, MD
Thankfully, the overall incidence of endophthalmitis in cataract surgery is rare. Recent data reveal rates ranging from 0.07% to 0.13%, with the multicenter ESCRS study reporting 0.38%.^1-3 When this complication does occur, however, it is devastating for the patient and the ophthalmologist alike.

From as early as the 1970s, studies have shown that the preoperative use of antibiotics minimizes the occurrence of endophthalmitis.^{4,/sup> In 1991, employing povidone-iodine was also found to lower endophthalmitis’ incidence.⁵ Today, povidone-iodine plus an antibiotic before surgery has become the accepted standard of care. Modern fluoroquinolones like moxifloxacin, gatifloxacin, and besifloxacin reduce infections in the ocular flora.^6,7}

THIRD- AND FOURTH-GENERATION AGENTS

Looking back, studies of the third-generation fluoroquinolones showed that agents’ penetration into the aqueous is an important characteristic in terms of endophthalmitis prevention. Increased penetration leads to better protection, according to retrospective studies.8 Regarding the spectrum of coverage of the thirdgeneration agents, it has been shown that ofloxacin and ciprofloxacin are virtually identical. The benefit associated with ofloxacin is that it penetrates into the aqueous better than ciprofloxacin.

In studying the fourth-generation antibiotics, investigators found that gatifloxacin penetrated the eye about as well as ofloxacin (Ocuflox; Allergan, Inc.).⁹ The minimum inhibitory concentrations (MICs) against gatifloxacin, however, were lower than those of ofloxacin, showing the former’s advantage. Vigamox (moxifloxacin; Alcon Laboratories, Inc.), which has better MICs than the thirdgeneration agents and is roughly comparable to gatifloxacin, showed superior penetration into the anterior chamber.¹⁰

Vigamox’s enhanced penetration goes hand in hand with its concentration: 0.5% compared with 0.3% for gatifloxacin. The two agents’ molecular designs allow for similar levels of penetration; Vigamox’s advantage here is the effect of a higher concentration of the active ingredient. Increased drop concentration means that more of the drug can penetrate into the corneal stroma and the aqueous. Therefore, a potential disadvantage of gatifloxacin is its concentration compared with that of Vigamox.

The branded gatifloxacin formulation Zymar (Allergan, Inc.) contains benzalkonium chloride (BAK). Blondeau has shown that MICs against Zymar were dramatically lower for organisms that were otherwise resistant to gatifloxacin and moxifloxacin.¹¹ Thus, Zymar’s BAK enhances the performance of the formulation. I do not believe, however, that BAK accompanies the drug into the aqueous. It should be emphasized that what happens inside the eye is totally dependent on the relative sensitivity of bacteria to the molecule that is in the eye.

Of course, an important factor in preventing endophthalmitis is the sterilization of the eye before surgery. Just as critical, however, is keeping the ocular surface sterile as much as possible after surgery until the incisions (particular clear corneal) have fully healed. In this regard, it has been shown that, in comparison with Vigamox, Zymar has a superior ability to kill otherwise resistant organisms such as methicillin-resistant Staphylococcus aureus.^12,13

CONCLUSION

Now available, Zymaxid (Allergan, Inc.) is formulated at 0.5%, addressing the main drawback of Zymar. The former can deliver higher levels of the active agent into the aqueous that are likely to be comparable to those of topical Vigamox. Research on this subject is needed. Zymaxid is preserved with BAK and also shares Zymar’s speed to kill and low MICs for otherwise resistant organisms. For these reasons, Zymaxid is my preferred drop.

John R. Wittpenn Jr, MD, is an associate clinical professor at the State University of New York in Stony Brook. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Wittpenn may be reached at (631) 941- 3363; jwittpenn@ocli.net.

Kattan HM,Flynn HW Jr,Pflugfelder SC,et al.Nosocomial endophthalmitis survey.Current incidence of infection after intraocular surgery.Ophthalmology.1991;98(2):227-238.
Javitt JC,Vitale S,Canner JK,et al.National outcomes of cataract extraction.Endophthalmitis following inpatient surgery.Arch Ophthalmol.1991;109(8):1085-1089.
Seal DV,Barry P,Gettinby G,et al.ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery:case for a European multicenter study.J Cataract Refract Surg.2006;32(3):396-406.
Allen HF,Mangiaracine AB.Bacterial endophthalmitis after cataract extraction.II.Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics.Arch Ophthalmol.1974;91:3-7.
Speaker MG,Menikoff JA.Prophylaxis of endophthalmitis with topical povidone-iodine.Ophthalmology.1991;98(12):1769- 1775.
Ou JI,Ta CN.Endophthalmitis prophylaxis. Ophthalmol Clin North Am.2006;19(4):449-456.
Bucci FA Jr.An in vivo study comparing the ocular absorption of levofloxacin and ciprofloxacin prior to phacoemulsification. Am J Ophthalmol.2004;137(2):308-312.
Jensen MK,Fiscella RG,Moshirfar M,Mooney B.Third- and fourth-generation fluoroquinolones:retrospective comparison of endophthalmitis after cataract surgery performed over 10 years.J Cataract Refract Surg.2008;34(9):1460-1467.
Wagner RS,Abelson MB,Shapiro A,Torkildsen G.Evaluation of moxifloxacin,ciprofloxacin,gatifloxacin,ofloxacin,and levofloxacin concentrations in human conjunctival tissue.Arch Ophthalmol.2005;123(9):1282-1283.
Holland EJ,Lane SS,Kim T,et al.Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.Cornea.2008;27(3):314-319.
Blondeau JM,Hesje C.Enhanced killing of methicillin-resistant Staphylococcus aureus (MRSA) strains with gatifloxacin and benzalkonium chloride.Poster presented at:ASCRS Symposium on Cataract,IOL and Refractive Surgery;April 3-8,2009;San Francisco,CA.Abstract P-16 Kattan HM,Flynn HW Jr,Pflugfelder SC,et al.Nosocomial endophthalmitis survey.Current incidence of infection after intraocular surgery.Ophthalmology.1991;98(2):227-238.
Javitt JC,Vitale S,Canner JK,et al.National outcomes of cataract extraction.Endophthalmitis following inpatient surgery.Arch Ophthalmol.1991;109(8):1085-1089. 3. Seal DV,Barry P,Gettinby G,et al.ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery:case for a European multicenter study.J Cataract Refract Surg.2006;32(3):396-406. 4. Allen HF,Mangiaracine AB.Bacterial endophthalmitis after cataract extraction.II.Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics.Arch Ophthalmol.1974;91:3-7. 5. Speaker MG,Menikoff JA.Prophylaxis of endophthalmitis with topical povidone-iodine.Ophthalmology.1991;98(12):1769- 1775. 6. Ou JI,Ta CN.Endophthalmitis prophylaxis. Ophthalmol Clin North Am.2006;19(4):449-456. 7. Bucci FA Jr.An in vivo study comparing the ocular absorption of levofloxacin and ciprofloxacin prior to phacoemulsification. Am J Ophthalmol.2004;137(2):308-312. 8. Jensen MK,Fiscella RG,Moshirfar M,Mooney B.Third- and fourth-generation fluoroquinolones:retrospective comparison of endophthalmitis after cataract surgery performed over 10 years.J Cataract Refract Surg.2008;34(9):1460-1467. 9.Wagner RS,Abelson MB,Shapiro A,Torkildsen G.Evaluation of moxifloxacin,ciprofloxacin,gatifloxacin,ofloxacin,and levofloxacin concentrations in human conjunctival tissue.Arch Ophthalmol.2005;123(9):1282-1283. 10. Holland EJ,Lane SS,Kim T,et al.Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.Cornea.2008;27(3):314-319. 11. Blondeau JM,Hesje C.Enhanced killing of methicillin-resistant Staphylococcus aureus (MRSA) strains with gatifloxacin and benzalkonium chloride.Poster presented at:ASCRS Symposium on Cataract,IOL and Refractive Surgery;April 3-8,2009;San Francisco,CA.Abstract P-16 12. Callegan MC,Novosad B.Efficacy of fourth-generation fluoroquinolones against gram-positive species commonly involved in ocular infections.Paper presented at:Annual Meeting of the Association for Research in Vision and Ophthalmology;April 30- May 4,2006;Fort Lauderdale,FL.
Snyder R,Callegan MC,Novosad B.Killing of methicillin-resistant S.aureus (MRSA) and S.epidermidis (MRSE) ocular isolates by fourth-generation fluoroquinolone ophthalmic solutions.Paper presented at:American Society for Refractive and Cataract Surgery Symposium;April 27-May 2,2007;San Diego,CA.

New Antibiotic-Plus- Steroid Formulation

Tobradex ST combines innovative technology with a tried-and-true product line.

BY DAVID A. GOLDMAN MD
Tobradex (tobramycin 0.3% plus dexamethasone 0.1%; Alcon Laboratories, Inc.) is a commonly prescribed medication in ophthalmic practice for a multitude of ocular conditions. Combining an antibiotic and steroid, the agent allows physicians to safely treat ocular inflammation in cases where there may be concern about bacterial overgrowth or underlying clandestine infection, such as blepharitis and corneal abrasions. Although steroids are tremendously effective for alleviating patients’ discomfort, they must be used judiciously to avoid deleterious side effects such as elevated IOP and delayed healing.

WHAT CHANGED?

To improve on their product, Alcon Laboratories, Inc., has released Tobradex ST—tobramycin 0.3% plus dexamethasone 0.05%. Although the concentration has been cut in half, the steroid’s bioavailability has remained the same by combining the formulation with xanthan gum. Via a proprietary ionic interaction, this new mixture appears similar to the original Tobradex while in the bottle. Upon contact with the ocular surface, however, the tear film disrupts the ionic interactions, leading to a sevenfold increase in viscosity (data on file, Alcon Laboratories, Inc.). This leads to increased retention time on the ocular surface and lid margin.

EXPERIENCE

I have found the new formulation to be very well tolerated by my patients. I have used it multiple situations such as after removing a foreign body, or preoperatively for cataract surgery, and I have been amazed with its successful treatment of acute exacerbations of blepharitis. This is not surprising considering that blepharitis is typically attributable to the overgrowth of Staphylococcus aureus and Staphylococcus epidermidis, both of which are susceptible to tobramycin. I believe Tobradex ST’s enhanced viscosity allows prolonged contact of both antibiotic and steroid with the lid margin, and that has resulted in a more rapid resolution of symptoms. This has also allowed me to be more flexible with my dosing schedule and less fearful of patients’ noncompliance. Overall, Tobradex ST represents a great improvement on an already excellent product.

David A. Goldman, MD, is an assistant professor of clinical ophthalmology at Bascom Palmer Eye Institute in Palm Beach Gardens, Florida. He is a consultant to Alcon Laboratories, Inc. Dr. Goldman may be reached at (561) 515-1543; dgoldman@med.miami.edu.

Ganciclovir 0.15% Gel for HSV

Zirgan replaces older antiviral medications that are no longer available.

BY ADRIANNE RESEK, CORRESPONDING EDITOR
Ocular herpes simplex virus (HSV) infection is estimated to manifest in 20,000 new cases and 28,000 recurring cases per year in the United States.¹ It comprises several potential visually impairing diseases and is considered to be a major cause of corneal opacity here and abroad.^2,3 In approximately 72% of cases, infection involves the cornea; in 41% of cases, there is lid or conjunctival involvement.⁴

TRIFLURIDINE

For many years, the only topical agent to treat HSV was trifluridine. Because this thymidine analogue is activated by cell and viral thymidine kinase, it targets the replication of DNA in both viral particles as well as the healthy corneal epithelium. This agent has proven efficacious against superficial keratitis, but it is associated with high levels of toxicity and is not recommended for longterm use.5,6 Trifluridine is preserved with thimerosal, which causes hypersensitivity in some patients. In addition, trifluridine 1% must be refrigerated, creating compliance-related difficulties. Due to trifluridine’s toxicity, physicians often integrate the use of systemic medications when treating HSV, which is never optimal.

SUPERIOR OPTION

The FDA recently approved the use of a new topical agent, ganciclovir 0.15% gel (Zirgan; Bausch + Lomb), for use in treating ocular HSV. Ganciclovir is a nucleoside analogue of guanosine, a broad-spectrum virustatic agent. Because ganciclovir is phosphorylated primarily by the viral enzyme thymidine kinase, the agent selectively targets the replication of DNA in the HSV viral particles and not the corneal epithelium. Activated ganciclovir inhibits viral DNA polymerase and incorporates itself to prevent viral DNA synthesis.7 Ganciclovir 0.15% gel has a neutral pH, with osmolarity numbers very similar to those of the natural tear. This quality enhances the agent’s tolerability for patients.

Ocular HSV infection remains a substantial public health concern, and ganciclovir 0.15% gel fills an important absence of treatment options. Many antiviral medications initially developed are no longer on the market due to cytotoxicity and poor tolerability. Trifluridine remains active, but toxicity is a concern. International multicenter trails indicate that ganciclovir 0.15% ophthalmic gel is at least as effective, and safer, than acyclovir 3% gel, its closest counterpart in Europe.⁸

CONCLUSION

First and foremost, physicians want efficacy for their patients. About 75% of epithelial defects healed within 7 days with Zirgan treatment.⁸ In addition, agents that are tolerable and convenient for patients encourage their compliance and increase their satisfaction. Zirgan requires instillation just five times per day compared with nine times per day with trifluridine, and the former does not require refrigeration. Recently approved, Zirgan is a positive addition to the ophthalmologist’s armamentarium.

Liesegang TJ,Melton LJ III,Daly PJ,Ilstrup DM,Epidemiology of ocular herpes simplex.Incidence in Rochester,Minnesota,1950 through 1982.Arch Ophthalmol.1989;107(8):1155-1159.
Biser SA,Perry HD,Herpes simplex keratitis.In:Puliafito CA,ed.Ophthalmic Hyperguide:Corneal and Anterior Segment Diseases. www.ophthalmic.hyperguides.com.Accessed August 6,2008.
Dawson CR,Togni B,Herpes simplex eye infections:clinical manifestations,pathogenesis,and management.Surv Ophthalmol. 1976;21(2):121-135.
Liesegang TJ.Epidemiology of ocular herpes simplex.Natural history in Rochester,Minnesota,1950 through 1982.Arch Ophthalmol. 1989;107(8):1160-1165.
Guess S,Stone DU,Chodosh J.Evidence-based treatment of herpes simplex virus keratitis:a systematic review.Ocul Surf. 2007;5(3):240-250.
Maudgal PC,Van Damme B,Missotten L.Corneal epithelial dysplasia after trifluridine use.Graefes Arch Clin Exp Ophthalmol. 1983;220(1):6-12.
Martin JC,Dvorak CA,Smee DF,et al.9-[(1,3-Dihydroxy-2-propoxy)methyl]guanine:a new potent and selective antiherpes agent. J Med Chem.1983;26:759-761.
Hoh HB,Hurley C,Claoue C,et al.Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis:a multicentre study.Br J Ophthalmol. 1996;80(2):140-143.

Artificial Tears: an Important Part of a Multipronged Dry Eye Approach

Systane Balance tear product contains a restorative lipid component.

BY JAMES A. KATZ, MD
When patients present complaining of dry eyes, I often find that their condition is not being managed appropriately. For example, in discussing their situation, I will discover that they are being treated for aqueous-deficient dry eye and not for meibomian gland dysfunction (MGD) or blepharitis. In these cases, I work to identify a second component in their diagnoses.

The deeper I dig during my examination of these patients, the more informed the decision I make will be and the better the likelihood is that patients will experience relief from their symptoms. Without a comprehensive investigation to dictate a similarly comprehensive treatment strategy, patients likely will not improve as much as they should.

DEFINING THE DISEASE

The definition of dry eye syndrome has changed during the past 5 to 10 years, further complicating its diagnosis and treatment. There is overlap among the conditions that eye care specialists classify as dry eye. Efforts by the 2004 Delphi Panel to change the term referring to aqueous tear deficiency from dry eye to dysfunctional tear syndrome were not entirely successful.¹ Many eye care specialists still refer to this cluster of signs and symptoms as dry eye.

Evaporative dry eye includes both the anterior and posterior forms of blepharitis. Posterior blepharitis and MGD are often considered to be the same entity. Although the syndromes overlap significantly, there are subtle differences with regard to their optimal treatment. In addition, some individuals may have an underlying systemic disorder, medication reaction, or vitamin A deficiency that is causing their condition. Such situations will require their

The patient’s signs and symptoms and the clinical examination should provide information that will guide treatment decisions. Common symptoms include ocular irritation, foreign body sensation, stinging, heavy eyelids, and tearing. Patients will also be troubled by symptoms that cause blurring, aberrations, and visual distortions. Those who are left untreated may develop more severe symptoms such as tear film instability, inflammation and irritation of the ocular surface, keratitis, and conjunctivitis.

Upon examination, the patient may have obvious signs such as red eyelid margins, flaky secretions resembling dandruff, plugged meibomian glands, lid margin thickening, and telangiectatic blood vessels. Further probing is needed to avoid missing a diagnosis.

SET

The simple acronym SET for symptoms, expression, and treatment is a helpful mnemonic for the differentiation of dry eye, blepharitis, and MGD. After reviewing the patient’s history, symptoms, and signs, I express the meibomian glands and examine the meibum. Healthy eyes will discharge a clear, thin oil, whereas that of unhealthy eyes may be a thicker, whiter meibum or even a buttery clump. Some patients may have no discharge at all.

own specific plans for management.

Update on a More Potent Corticosteroid

Durezol achieves similar clinical results at less than half the dose of the old gold standard.

ERIC D. DONNENFELD, MD

The administration of steroids has long been a common practice after most ocular surgical procedures. This use, however, has not mirrored what other medical specialties have discovered: dosing a potent steroid, in a pulsed fashion, well before the trauma of surgery provides the most benefit. In other words, preventing inflammation is more effective than treating inflammation. This concept is based on two ideas, one borrowed from general surgery and the other from the field of acute brain trauma.

RESPONSE TO SURGICAL STRESS

For many years, physicians have predosed patients with steroids prior to surgical intervention, whether major or minimally invasive. The anti-inflammatory and immunemodulating effects of glucocorticoids have been known for decades. These agents have found extensive therapeutic use in a wide range of diseases in which inflammatory responses are a main feature. Topical steroids reduce inflammation by increasing the production of protein that inhibits phospholipase A. They also decrease the formation of prostaglandins and leukotrienes and block the production and release of inflammatory cytokines.

Trauma from a surgical procedure elicits an inflammatory stress response, which is often excessive and can contribute to postoperative morbidity and untoward outcomes. Surgeons attempt to modulate this potentially deleterious response by downregulating the patient’s inflammatory response to surgery. Holte and Kehlet performed a systematic review of randomized, controlled, clinical trials involving major surgical procedures.¹ Their investigation revealed that the steroid’s administration before surgery reduced local edema and pain after many of the procedures. Importantly, the timing of steroidal administration was critical: steroids dosed less than 1 to 2 hours prior to surgery seemed to have less effect, potentially because the protein-mediated onset of action for steroids takes about this long.¹

TISSUE’S PRESERVATION

The second concept regarding steroidal use involves the preservation of tissue secondary to acute brain trauma. It is widely accepted that the pulsed administration of high-dose steroids immediately after injury helps to protect neural tissue. ² Because the corneal endothelium and the retina are of neuroectodermal origin (like the brain and spinal cord), they may also benefit from pulsed high-dose steroids to minimize the effects of surgical trauma.

RESEARCH

My colleagues and I tested a novel pulsed dosing regimen in which two steroids (difluprednate ophthalmic emulsion [Durezol; Alcon Laboratories, Inc.] and generic prednisolone acetate suspension) were dosed 10 times starting 2 hours before cataract surgery and for 2 weeks after. This prospective, multicenter, double-masked, randomized, contralateral eye study involved 63 patients (126 eyes). We found that the administration of Durezol in this pulse-dosed fashion provided significantly better visual acuity and less corneal edema (measured via pachymetry) on day 1 when compared to prednisolone. In addition, there was significantly less endothelial cell loss at day 30 and less macular edema, as seen using optical coherence tomography, on days 15 and 30 in the Durezol-treated patients.³

Our study not only demonstrated the utility of this pulsed dosing regimen, but it also showed the superiority of Durezol, a relatively new topical steroid. For years, ophthalmic surgeons have thought of prednisolone acetate as the gold standard of topical steroids. After more experience with Durezol, many are realizing firsthand that this steroid provides a more robust and potent anti-inflammatory effect. This idea was borne out in the literature in a uveitis study conducted by Foster et al, in which the agent dosed four times a day provided a greater anti-inflammatory effect than Pred Forte (Allergan, Inc.) dosed eight times a day.4 Surgeons now have a steroid that achieves similar clinical results at less than half the dose of the old gold standard.

A recent study by Tajika et al provides more evidence regarding the comparative potencies of Durezol and other steroids.5 The study was designed to determine the glucocorticoid receptor-binding affinity of Durezol and its active metabolite, 17-butyrate, compared to that of prednisolone, betamethasone, fluorometholone, and dexamethasone. A glucocorticoid receptor-binding test was performed to evaluate the Ki value of each steroid. The Ki value is a dissociation constant that is an inverse indication of the affinity for a receptor (the lower the Ki value, the higher the affinity). The active metabolite 17-butyrate had the lowest Ki value (6.11 X 10^-11 mol/L) and was significantly more active than prednisolone (Ki value = 3.4 X 10^-9 mol/L). This revealed that the glucocorticoid binding affinity for the active metabolite of Durezol was 56 times stronger than prednisolone.

POSTERIOR SEGMENT USES

Two small case-controlled studies published by Nakano et al showed Durezol’s potential utility in the posterior segment. In the first study, Durezol was compared with a sub- Tenon’s injection of triamcinolone and was found to be similarly effective for the reduction of retinal thickness in patients with refractory diabetic macular edema.6 The second investigation compared Durezol with betamethasone (considered six to eight times stronger than prednisolone acetate) for the treatment of diffuse diabetic macular edema prior to vitrectomy. Durezol reduced retinal thickness and improved visual acuity more effectively than betamethasone after 1 month of treatment.⁷ Many vitreoretinal specialists are routinely using Durezol to treat cystoid macular edema and feel it has significantly reduced the need for intravitreal steroid injections.

CONCLUSION

Those of us treating moderate-to-severe inflammatory disease now have a stronger steroid that can replace agents with regimens that sometimes exceed hourly dosing. I routinely use Durezol to treat inflammatory conditions such as uveitis, toxic anterior segment syndrome, cystoid macular edema, and diffuse lamellar keratitis following LASIK. Even for procedures that may not elicit as much inflammation, we have an option that results in more rapid visual recovery and decreased discomfort and that may also reduce dosing from q.i.d. to b.i.d. or less often. I now routinely use Durezol for cataract surgery and have reduced my postoperative dosing schedule to b.i.d for 2 weeks and q.d. for a third week. Clearly, more studies are needed, but I can speak from experience that this drug is an exciting and valuable addition to our treatment arsenal.

Eric D. Donnenfeld, MD, is a professor of ophthalmology at NYU and a trustee of Dartmouth Medical School in Hanover, New Hampshire. Dr. Donnenfeld is in private practice with Ophthalmic Consultants of Long Island in Rockville Centre, New York. He is a consultant to Alcon Laboratories, Inc. Dr. Donnenfeld may be reached at (516) 766-2519; eddoph@aol.com.

Holte K,Kehlet H.Perioperative single-dose glucocorticoid administration:pathophysiologic effects and clinical implications. J Am Coll Surg.2002;195(5):694-712.
Bracken MB,Shepard MJ,Holford TR,et al.Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury:1-year follow up.Results of the third National Acute Spinal Cord Injury randomized controlled trial.J Neurosurg. 1998;89(5):699-706.
Donnenfeld,ED,Holland,EJ,Solomon,KD,et al.A randomized controlled trial of the efficacy and safety of pulse dosed difluprednate versus prednisolone acetate in cataract surgery.Am J Ophthalmol.In press.
Foster CS,Davanzo R,Flynn TE,et al.Prednisolone acetate in cataract surgery.Durezol (difluprednate ophthalmic emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis.J Ocul Pharmacol Ther. 2010;26(5):475-483.
Tajika T,Isowaki A,Sakaki H.Ocular distribution of difluprednate ophthalmic emulsion 0.05% in rabbits. J Ocul Pharmacol Ther.2011;27(1):43-49.
Nakano S,Yamamoto T,Kirii E,et al.Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema.Graefes Arch Clin Exp Ophthalmol. 2010;248(6):805-810.
Nakano S,Yamamoto T,Kirii E,et al.Treatment of diffuse diabetic macular oedema using steroid eye drops [published online ahead of print January 14,2011].Acta Ophthalmol.doi:10.1111/j.1755-3768.2010.02066.x.

Bromfenac Ophthalmic Solution 0.09%

Penetration and potency are now available in Bromday, a once-daily NSAID formulation.

STUDIES

For postoperative inflammation on day 15, the patients receiving Bromday had a summed ocular inflammation score level of just 1.1 compared with 2.8 for the patients assigned to placebo (^P < .0001 for days 3, 8, 15, and 22). Patients were questioned about their pain level on postoperative day 1, after having received a total of three drops of Bromday. Slightly fewer than 95% of the treated patients reported “none” versus 70.5% for placebo (data on file with Ista Pharmaceuticals, Inc.).

CONCLUSION

High-Concentration Moxifloxacin

Moxeza, a fourth-generation fluoroquinolone, delivers a high dosage of moxifloxacin to the ocular surface.

Moxeza can be delivered in high concentration to the tissues of the ocular surface.1 This is beneficial when treating bacterial conjunctivitis or a bacterial infection of the cornea. In a randomized, double-masked, parallel group study, conjunctival concentrations of moxifloxacin were measured in 130 patients scheduled for phacoemulsification and implantation of an IOL. The patients were randomized to receive a one-drop instillation of Vigamox or Moxeza, and then conjunctival biopsies were obtained. The results showed that the conjunctival moxifloxacin concentration in patients treated with Moxeza was 1.8-fold higher than in patients treated with Vigamox (C_max = 43.8 μg/g for Moxeza achieved at 0.25 hours vs C_max = 24.1 μg/g at 0.5 hours for Vigamox). This demonstrates that Moxeza is able to penetrate the conjunctival tissues. Moxeza was also found to provide a larger total tissue exposure than Vigamox. These findings regarding tissue-penetration data are important because of the concentration-dependent nature of fluoroquinolones in the treatment of bacterial infections. This translates into a greater eradication of bacteria, which is important in the treatment of bacterial conjunctivitis.

DELIVERY SYSTEM

Lindstrom R,Lane S,Cottingham A,et al.Conjunctival concentrations of a new ophthalmic solution formulation of moxifloxacin 0.5% in cataract surgery patients. J Ocul Pharmacol Ther. 2010;26(6):591-595.
Balzil CL,Weeks RW,Besinger RW,et al.Prophylactic treatment with Vigazera,Zymar,or Zymaxid of Staphylococcus aureus infections in the rabbit anterior chamber.Paper presented at:Ocular Microbiology and Immunology Group 44th Annual Meeting;October 15,2010;Chicago,IL.Abstract 11.

The Advantages of Gatifloxacin 0.5%

Zymaxid’s higher concentration, preservation with BAK, speed to kill, and MICs enhance its efficacy.

BY JOHN R. WITTPENN JR, MD
Thankfully, the overall incidence of endophthalmitis in cataract surgery is rare. Recent data reveal rates ranging from 0.07% to 0.13%, with the multicenter ESCRS study reporting 0.38%.1-3 When this complication does occur, however, it is devastating for the patient and the ophthalmologist alike.

From as early as the 1970s, studies have shown that the preoperative use of antibiotics minimizes the occurrence of endophthalmitis.⁴ In 1991, employing povidone-iodine was also found to lower endophthalmitis’ incidence.5 Today, povidone-iodine plus an antibiotic before surgery has become the accepted standard of care. Modern fluoroquinolones like moxifloxacin, gatifloxacin, and besifloxacin reduce infections in the ocular flora.^6,7

THIRD- AND FOURTH-GENERATION AGENTS

CONCLUSION

Kattan HM,Flynn HW Jr,Pflugfelder SC,et al.Nosocomial endophthalmitis survey.Current incidence of infection after intraocular surgery.Ophthalmology.1991;98(2):227-238.
Javitt JC,Vitale S,Canner JK,et al.National outcomes of cataract extraction.Endophthalmitis following inpatient surgery.Arch Ophthalmol.1991;109(8):1085-1089.
Seal DV,Barry P,Gettinby G,et al.ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery:case for a European multicenter study.J Cataract Refract Surg.2006;32(3):396-406.
Allen HF,Mangiaracine AB.Bacterial endophthalmitis after cataract extraction.II.Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics.Arch Ophthalmol.1974;91:3-7.
Speaker MG,Menikoff JA.Prophylaxis of endophthalmitis with topical povidone-iodine.Ophthalmology.1991;98(12):1769- 1775.
Ou JI,Ta CN.Endophthalmitis prophylaxis. Ophthalmol Clin North Am.2006;19(4):449-456.
Bucci FA Jr.An in vivo study comparing the ocular absorption of levofloxacin and ciprofloxacin prior to phacoemulsification. Am J Ophthalmol.2004;137(2):308-312.
Jensen MK,Fiscella RG,Moshirfar M,Mooney B.Third- and fourth-generation fluoroquinolones:retrospective comparison of endophthalmitis after cataract surgery performed over 10 years.J Cataract Refract Surg.2008;34(9):1460-1467.
Wagner RS,Abelson MB,Shapiro A,Torkildsen G.Evaluation of moxifloxacin,ciprofloxacin,gatifloxacin,ofloxacin,and levofloxacin concentrations in human conjunctival tissue.Arch Ophthalmol.2005;123(9):1282-1283.
Holland EJ,Lane SS,Kim T,et al.Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.Cornea.2008;27(3):314-319.
Blondeau JM,Hesje C.Enhanced killing of methicillin-resistant Staphylococcus aureus (MRSA) strains with gatifloxacin and benzalkonium chloride.Poster presented at:ASCRS Symposium on Cataract,IOL and Refractive Surgery;April 3-8,2009;San Francisco,CA.Abstract P-16
Callegan MC,Novosad B.Efficacy of fourth-generation fluoroquinolones against gram-positive species commonly involved in ocular infections.Paper presented at:Annual Meeting of the Association for Research in Vision and Ophthalmology;April 30- May 4,2006;Fort Lauderdale,FL.
Snyder R,Callegan MC,Novosad B.Killing of methicillin-resistant S.aureus (MRSA) and S.epidermidis (MRSE) ocular isolates by fourth-generation fluoroquinolone ophthalmic solutions.Paper presented at:American Society for Refractive and Cataract Surgery Symposium;April 27-May 2,2007;San Diego,CA.

New Antibiotic-Plus- Steroid Formulation

Tobradex ST combines innovative technology with a tried-and-true product line.

WHAT CHANGED?

EXPERIENCE

I have found the new formulation to be very well tolerated by my patients. I have used it multiple situations such as after removing a foreign body, or preoperatively for cataract surgery, and I have been amazed with its successful treatment of acute exacerbations of blepharitis. This is not surprising considering that blepharitis is typically attributable, to the overgrowth of Staphylococcus aureus and Staphylococcus epidermidis, both of which are susceptible to tobramycin. I believe Tobradex ST’s enhanced viscosity allows prolonged contact of both antibiotic and steroid with the lid margin, and that has resulted in a more rapid resolution of symptoms. This has also allowed me to be more flexible with my dosing schedule and less fearful of patients’ noncompliance. Overall, Tobradex ST represents a great improvement on an already excellent product.

Ganciclovir 0.15% Gel for HSV

Zirgan replaces older antiviral medications that are no longer available.

TRIFLURIDINE

For many years, the only topical agent to treat HSV was trifluridine. Because this thymidine analogue is activated by cell and viral thymidine kinase, it targets the replication of DNA in both viral particles as well as the healthy corneal epithelium. This agent has proven efficacious against superficial keratitis, but it is associated with high levels of toxicity and is not recommended for longterm use.^5,6 Trifluridine is preserved with thimerosal, which causes hypersensitivity in some patients. In addition, trifluridine 1% must be refrigerated, creating compliance-related difficulties. Due to trifluridine’s toxicity, physicians often integrate the use of systemic medications when treating HSV, which is never optimal.

SUPERIOR OPTION

The FDA recently approved the use of a new topical agent, ganciclovir 0.15% gel (Zirgan; Bausch + Lomb), for use in treating ocular HSV. Ganciclovir is a nucleoside analogue of guanosine, a broad-spectrum virustatic agent. Because ganciclovir is phosphorylated primarily by the viral enzyme thymidine kinase, the agent selectively targets the replication of DNA in the HSV viral particles and not the corneal epithelium. Activated ganciclovir inhibits viral DNA polymerase and incorporates itself to prevent viral DNA synthesis.⁷ Ganciclovir 0.15% gel has a neutral pH, with osmolarity numbers very similar to those of the natural tear. This quality enhances the agent’s tolerability for patients.

CONCLUSION

First and foremost, physicians want efficacy for their patients. About 75% of epithelial defects healed within 7 days with Zirgan treatment.8 In addition, agents that are tolerable and convenient for patients encourage their compliance and increase their satisfaction. Zirgan requires instillation just five times per day compared with nine times per day with trifluridine, and the former does not require refrigeration. Recently approved, Zirgan is a positive addition to the ophthalmologist’s armamentarium.

Liesegang TJ,Melton LJ III,Daly PJ,Ilstrup DM,Epidemiology of ocular herpes simplex.Incidence in Rochester,Minnesota,1950 through 1982.Arch Ophthalmol.1989;107(8):1155-1159.
Biser SA,Perry HD,Herpes simplex keratitis.In:Puliafito CA,ed.Ophthalmic Hyperguide:Corneal and Anterior Segment Diseases. www.ophthalmic.hyperguides.com.Accessed August 6,2008.
Dawson CR,Togni B,Herpes simplex eye infections:clinical manifestations,pathogenesis,and management.Surv Ophthalmol. 1976;21(2):121-135.
Liesegang TJ.Epidemiology of ocular herpes simplex.Natural history in Rochester,Minnesota,1950 through 1982.Arch Ophthalmol. 1989;107(8):1160-1165.
Guess S,Stone DU,Chodosh J.Evidence-based treatment of herpes simplex virus keratitis:a systematic review.Ocul Surf.2007;5(3):240-250.
Maudgal PC,Van Damme B,Missotten L.Corneal epithelial dysplasia after trifluridine use.Graefes Arch Clin Exp Ophthalmol. 1983;220(1):6-12.
Martin JC,Dvorak CA,Smee DF,et al.9-[(1,3-Dihydroxy-2-propoxy)methyl]guanine:a new potent and selective antiherpes agent. J Med Chem.1983;26:759-761.
Hoh HB,Hurley C,Claoue C,et al.Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis:a multicentre study.Br J Ophthalmol. 1996;80(2):140-143. 2007;5(3):240-250.

Artificial Tears: an Important Part of a Multipronged Dry Eye Approach

Systane Balance tear product contains a restorative lipid component.

DEFINING THE DISEASE

The definition of dry eye syndrome has changed during the past 5 to 10 years, further complicating its diagnosis and treatment. There is overlap among the conditions that eye care specialists classify as dry eye. Efforts by the 2004 Delphi Panel to change the term referring to aqueous tear deficiency from dry eye to dysfunctional tear syndrome were not entirely successful.¹ Many eye care specialists still refer to this cluster of signs and symptoms as dry eye.

DIAGNOSTIC CLUES

SET

The simple acronym SET for symptoms, expression, and treatment is a helpful mnemonic for the differentiation of dry eye, blepharitis, and MGD. After reviewing the patient’s history, symptoms, and signs, I express the meibomian glands and examine the meibum. Healthy eyes will discharge a clear, thin oil, whereas that of unhealthy eyes may be a thicker, whiter meibum or even a buttery clump. Some patients may have no discharge at all.

Patients with abnormal meibum are likely to have MGD, and those with none, or a thin oil, are likely to have dry eyes. Often, patients do not fall neatly into one category or the other; instead, they have both conditions. For this reason, there is an overlap in treatment. It is important, however, to identify all of the components for proper management.

COMBINED TREATMENT

Patients with dry eye will require management that addresses their aqueous deficiency, and those with MGD and blepharitis may benefit from therapy that replaces their lipid layer. I instruct all patients to practice lid hygiene, which includes warm compresses to loosen secretions and reduce inflammation as well as over-the-counter lid scrubs to combat the bacterial overload. Patients’ education regarding these methods is important to enhance their compliance.

Treatment strategies for acute blepharitis and MGD have three main goals: to reduce inflammation, decrease bacteria, and replace the lipid layer. Although I tailor the specific choices of agents to the individual patient, I include a topical steroid to target inflammation or a steroid-antibiotic combination, such as Tobradex ST (Alcon Laboratories, Inc.) to eliminate bacteria. Omega-3 preparations are important for restoring the lipid layer, and I may prescribe them in combination with doxycycline or topical azithromycin (AzaSite; Inspire Pharmaceuticals, Inc.).

TEAR REPLACEMENT

Some chronic cases of blepharitis or MGD may respond to treatment with an artificial tear product that contains a restorative lipid component. Both Systane Balance Lubricant Eye Drops (Alcon Laboratories, Inc.) and Soothe XP Emollient Eye Drops (Bausch + Lomb) can be useful.

I will typically use Systane Balance for my patients with chronic disease, because studies² have shown the product improves tear film breakup time for more than 2 hours with just a single drop (data on file, Alcon Laboratories, Inc.). For patients who have dry eye only, aqueous drops are sufficient. I will also prescribe an antibiotic like doxycycline or cyclosporine for patients who have chronically dry eyes. In some acute cases, a topical steroid and possibly punctal plugs may be needed.

Eye care specialists must perform a comprehensive examination of patients who present with dry eyes. Although there are similarities among this condition, blepharitis, and MGD, subtle adjustments to treatment are required for optimal management and happy, healthy patients.

James A. Katz, MD, is the medical director of the Golf Laser Vision Center and a corneal specialist at The Midwest Center for Sight in Chicago. He is a consultant to Alcon Laboratories, Inc. Dr. Katz may be reached at (847) 824-3127; jkatz@tmcfs.com.

Behrens A,Doyle JJ,Stern L,et al.Dysfunctional tear syndrome:a Delphi approach to treatment recommendations.Cornea. 2006;25(8):900-907.
Ousler GW,Michaelson C,Christensen MT.An evaluation of tear film breakup time extension and ocular protection index scores among three marketed lubricant eye drops.Cornea.2007;26(8):949-952.

A Once-Daily Option for Episodic and Chronic Allergy Sufferers

Lastacaft (alcaftadine ophthalmic solution 0.25%) was recently approved by the FDA.

BY JODI LUCHS, MD
The introduction of Lastacaft (alcaftadine ophthalmic solution 0.25%; Allergan, Inc.) to the ocular allergy market provides another valuable once-daily option for patients with allergic conjunctivitis. Approved by the FDA in July 2010, this topical H1 histamine receptor agonist lends itself well to the treatment of both chronic and episodic ocular allergies. Through its 16-hour duration, Lastacaft has the ability to improve the level of compliance of and convenience for ocular allergy sufferers.

DUAL MECHANISM

Like many of the modern ocular allergy drops on the market, Lastacaft belongs to the class of drugs combining an antihistamine and mast cell stabilizer. Among the other drugs in this class are Patanol (olapatadine 0.1%; Alcon Laboratories, Inc.); Pataday (olapatadine HCl ophthalmic solution 0.2%; Alcon Laboratories, Inc.); Elestat (epinastine HCL 0.05%; Inspire Pharmaceuticals, Inc.); Bepreve (bepotastine besilate 1.5%; Ista Pharmaceuticals, Inc.); Optivar (azelastine 0.05%; Meda Pharmaceuticals); and Zaditor (ketotifen fumarate 0.035%; Novartis Pharmaceuticals). Combination drugs act to prevent histamine from binding to the H1 receptors on the conjunctiva, while simultaneously preventing the release of cytoplasmic granules by mast cells.

Drugs like Lastacaft offer patients rapid relief from episodic itch, while also providing comprehensive relief of seasonal and perennial allergies through mast cell stabilization. For these patients, Lastacaft can suppress the allergic response, thus decreasing the frequency and severity of allergic flare-ups. Currently, the only other topical allergy drop indicated for once-daily use is Pataday.

ANTIGEN CHALLENGE TRIALS

Onset
The FDA’s approval of Lastacaft was based on phase 3 conjunctival antigen challenge trials.1 In this trial design, patients with a demonstrated sensitivity to certain antigens are enrolled. These patients are given one drop of the study medication in one eye and one drop of a placebo drop in the other. This is done in a masked fashion. Fifteen minutes later, a known concentration of the antigen is instilled directly on the ocular surface. Symptoms are evaluated 3, 5, and 7 minutes after instillation. This type of study provides useful data regarding the onset of action in reducing itch. To achieve FDA approval, a drug must show a one-unit reduction in itch scores compared with placebo. In the majority of these patients, Lastacaft was found to significantly improve the symptoms of ocular itch within 3 minutes.

Duration

In the duration arm of the trial, one drop of Lastacaft and one drop of placebo were administered to the ocular surface 16 hours before the antigen challenge. The itch scores were then measured at various time points after the antigen was introduced. Lastacaft was found to yield a statistically significant reduction in itch scores compared to placebo and also compared to baseline itch scores.¹ Because the drug lasted 16 hours (the estimated waking hours of most people) after the single administration of a drop, it met the FDA’s criteria for approval as a once-daily drop.

OVER-THE-COUNTER MEDICATIONS

The once-daily convenience of a medication like Lastacaft may provide a favorable alternative to over-thecounter antihistamine/vasoconstrictor drops, which can be addictive for and potentially toxic to allergy sufferers. These drugs, such as Visine (McNeil-PPC, Inc.), Naphcon (Alcon Laboratories, Inc.), and Opcon (Bausch + Lomb), provide temporary relief from itch and redness but often ultimately serve to conceal the underlying problem. They also have a significant rebound effect, and patients feel compelled to use the drops repeatedly throughout the day. Patients’ education about the mechanisms and drawbacks of these drops is vital. Individuals with chronic ocular allergies need treatment with an effective prescription medication.

THE PROMISE OF LASTACAFT

Patients who suffer from allergic conjunctivitis will appreciate being able to instill a single drop of Lastacaft in the morning and not needing to worry about rebound itch throughout the day. Treating allergic itch, once it has begun, is much more problematic than preventing it. Particularly for patients who wear contact lenses, there is great expediency in not having to worry about rebound itch, which often necessitates removing the contact lenses and reapplying the drug. Rebound itch can significantly affect daily function, so a true once-daily allergy drop should significantly improve patients’ compliance and convenience.

Jodi Luchs, MD, is an assistant clinical professor of ophthalmology and visual sciences at the Albert Einstein College of Medicine in Bronx, New York, codirector of the Department of Refractive Surgery at the North Shore/Long Island Jewish Health System in New York, and director of clinical research and cornea/external disease at South Shore Eye Care in Wantagh, New York. He is a consultant to Allergan, Inc.; Inspire Pharmaceuticals, Inc.; and Ista Pharmaceuticals, Inc. Dr. Luchs may be reached at (516) 785-3900; jluchs@aol.com.

Torkildsen G,Shedden A.The safety and efficacy of alcaftadine 0.25% ophthalmic solution for the prevention of itching associated with allergic conjunctivitis.Curr Med Res Opin.2011;27:623-631.

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ERIC D. DONNENFELD, MD

STEPHEN G. SLADE, MD

STEVEN J. DELL, MD

WILLIAM B. TRATTLER, MD

JOHN F. DOANE, MD

JOHN A. HOVANESIAN, MD

RICHARD J. MACKOOL, MD

R. DOYLE STULTING, MD, PHD

Bromfenac Ophthalmic Solution 0.09%

STUDIES

CONCLUSION

High-Concentration Moxifloxacin

DELIVERY SYSTEM

The Advantages of Gatifloxacin 0.5%

THIRD- AND FOURTH-GENERATION AGENTS

CONCLUSION

New Antibiotic-Plus- Steroid Formulation

WHAT CHANGED?

EXPERIENCE

Ganciclovir 0.15% Gel for HSV

TRIFLURIDINE

SUPERIOR OPTION

CONCLUSION

Artificial Tears: an Important Part of a Multipronged Dry Eye Approach

DEFINING THE DISEASE

SET

Update on a More Potent Corticosteroid

ERIC D. DONNENFELD, MD

RESPONSE TO SURGICAL STRESS

TISSUE’S PRESERVATION

RESEARCH

POSTERIOR SEGMENT USES

CONCLUSION

Bromfenac Ophthalmic Solution 0.09%

STUDIES

CONCLUSION

High-Concentration Moxifloxacin

DELIVERY SYSTEM

The Advantages of Gatifloxacin 0.5%

THIRD- AND FOURTH-GENERATION AGENTS

CONCLUSION

New Antibiotic-Plus- Steroid Formulation

WHAT CHANGED?

EXPERIENCE

Ganciclovir 0.15% Gel for HSV

TRIFLURIDINE

SUPERIOR OPTION

CONCLUSION

Artificial Tears: an Important Part of a Multipronged Dry Eye Approach

DEFINING THE DISEASE

DIAGNOSTIC CLUES

SET

COMBINED TREATMENT

TEAR REPLACEMENT

A Once-Daily Option for Episodic and Chronic Allergy Sufferers

DUAL MECHANISM

ANTIGEN CHALLENGE TRIALS

OVER-THE-COUNTER MEDICATIONS

THE PROMISE OF LASTACAFT

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