Which drop do you use, and when?

Surgeons vary anti-inflammatories, antibiotics to improve healing.

Drops for phaco surgery have created a tray full of bottles that surgeons can prescribe for their patients. The choices between which bottle to prescribe and what regimen to follow has presented as many choices as the method to crack the nucleus.

Physicians can prescribe drops to handle inflammation, infection and irrigation needs of small incision surgery. The advent of fluoroquinolones alone created a marketing war as researchers attempt to find the best possible characteristics of each drug.

And, one researcher concluded, drops may not be needed postoperatively, although most surgeons follow heavy prescription regimens to ensure the best results. Researchers presented their regimens at the American Society of Cataract and Refractive Surgery (ASCRS) meeting in Seattle.

No drops postoperatively

---Dr. Kershner uses viscoelastic intraoperatively instead of irrigation drops, which he said can cause defects.

Robert M. Kershner, MD, said eye drops are no longer necessary with small incision refractive cataract surgery.

“Although there are a lot of drops that we use for both antibiosis and postoperative anti-inflammatory treatment, let’s take a good, hard, objective look at whether or not we need to do this,” he said.

Most surgeons use topical povidone iodine preoperatively and then divide efforts between subconjunctival antibiotic injections or antibiotics in the irrigation solution.

“Eye drops are, in fact, necessary be fore surgery,” Dr. Kershner said. “Antibiotic prophylaxis is very effective if it’s used prior to or at the time of surgery.”

If the preoperative preparation is adequate, then eye drops are not necessary during the surgery or afterward, he said.

Also, intraoperatively he uses viscoelastic instead of irrigation drops, which he said can cause defects and tie up a technician who could be performing other tasks.

Dr. Kershner suggested substituting one drop of 2.5% hydroxypropyl methylcellulose (HPMC) in lieu of irrigation during surgery. He applies one drop of HPMC once at the start of the case. It provides 1.5 times magnification, it coats and protects the cornea, and it frees up a scrub assistant to do more important tasks, he said.

He added that 2.5% HPMC is the thickest and most viscous product available. Ocucoat (Bausch & Lomb) works well but is slightly less viscous at 2%. Xylocaine jelly (lidocaine hydro chloride; Astra) can be used to provide additional anesthesia.

Dr. Kershner did a prospective evaluation of small incision cataract surgery with and without drops of 322 eyes of 169 patients. He divided them into two groups that used balanced salt solution irrigation during the procedure and an antibiotic steroid combination postoperatively.

In the second group, he used just HPMC once at the start of the case, a subconjunctival injection at the time of surgery and no postoperative eye drops.

He followed up the patients at 1 day, 1 week, 1 month and at 3 months. He recorded visual acuity, inflammation, infection and corneal clarity on each one of the postoperative visits and found no statistically significant differences between the groups.

“Over the postoperative course, the group that got the drops tended to have a little bit more superficial punctate keratitis,” Dr. Kershner said. “As you might imagine, they had a lot more irrigation and had a lot more things going into the eye. Intraoperative irrigation and postoperative eye drops are not necessary. Isn’t it time to change the routine?”

Prophylactic effects

---Eye drops are necessary before surgery. Antibiotic prophylaxis is very effective if it’s used prior to or at the time of surgery, according to Dr. Kershner.

However, most surgeons do use drops that relieve the eye from infections and the inflammation that stems from invasive surgery.

Another researcher, Kerry D. Solomon, MD, conducted a small-scale study that showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as steroids but have fewer side effects.

“I happen to be a believer in using drops after cataract surgery,” he said. “Even though we are very good at what we are doing with our routine surgery, I think we certainly do need an anti-inflammatory, and most certainly an antibiotic of sorts after surgery.”

Previous multi-center randomized trials have shown 40% to 50% failure rates with patients who received an anti-inflammatory agent after routine surgery. Most surgeons treat the eye with strong steroids postoperatively. But these drugs can raise intraocular pressure (IOP) or open the eye up to opportunistic infections, they said. Some surgeons have switched to weaker steroids, such as TobraDex (tobramycin dexamethasone; Alcon), which do not penetrate the eye so well, Dr. Solomon said.

Dr. Solomon conducted a study to compare strong steroids with NSAIDs. He designed a prospective, randomized trial of 40 patients to compare the NSAID ketorolac with one of the newer potent steroids, Vexol (rimexolone; Alcon).

He used a Kowa laser cell and flare meter measurement to provide objective measurements in addition to the slit lamp exam.

He did not administer any steroids or NSAIDs during the course of the study. All patients received an antibiotic alone for the first 24 hours. At day 1, they were randomized to receive one of the two agents.

He found no difference in slit lamp exam scores for cell and flare, and he found no difference in foreign body sensation, ciliary flush or conjunctival erythema.

Patients filled out questionnaires, and Dr. Solomon said he found no difference in the incidence of burning and stinging associated with the nonsteroidals. He also found no trends in postoperative IOP. The Kowa cell and flare measurements indicated quicker stabilization and resolution of inflammation in the Acular (ketorolac tromethamine; Allergan) patients compared to the Vexol patients. While these results are not statistically significant possibly due to small sample sizes. The trend indicates that Acular may stabilize the aqueous barrier sooner than steroids.

NSAIDs, such as Acular, may make more sense than the conventional steroids for cataract.

“Intraoperatively, they may blunt the inflammatory response and inhibit possible miosis. Postoperatively, they reduce inflammation and provide CME prophylaxis. Conventional NSAIDs, such as Acular or Voltaren (diclofenac sodium; CIBA Vision) are far more versatile with few if any associated risks. There have been some recent reports of corneal thinning associated with the use of generic NSAIDs. I have no personal experience with the use of those nonsteroidals. We have not seen these problems with any of the conventional, nongeneric NSAID studies performed at our institution,” Dr. Solomon said.

Accepted regimens

Although no drugs can eradicate all ocular organisms, some standard perioperative regimens have been accepted as being the most effective at reducing them to controllable levels. According to Calvin W. Roberts, MD, a combination of a skin prep with 10% povidone iodine, combined with the 3 days of preoperative use of a topical fluoroquinolone, is the most effective prophylaxis.

“The main goal of all of our regimens is to reduce the incidence of endophthalmitis and reduce the number of organisms on the ocular surface,” he said. “It’s impossible, with any of our present agents that we have available, to actually sterilize the ocular surface in every case, but we’re trying to reduce the number of organisms to as great an extent as possible.”

A threshold level of bacteria exists in order for endophthalmitis to occur. Primate studies show that between 1,000 and 10,000 organisms are needed before endophthalmitis establishes itself.

“It’s very important to sterilize the sur face, because you don’t want to drag in 10,000 organisms on your IOL or with your instruments,” Dr. Roberts said.

To test this, he randomized patients undergoing phacoemulsification into three groups. The first group began their antibiotics just when they arrived at the ambulatory surgery center and received their drops four times per day beginning an hour prior to surgery.

The second group began their drops the day prior to surgery and also received them in the ambulatory surgery center. The third group started their drops 3 days prior to surgery along with the drops in the ambulatory surgery center.

The randomized, prospective study took anterior chamber samples just at the start of the surgery and sent them for analysis.

Researchers found that patients who had 3 days of preoperative antibiotics had a statistically significant increase in the concentration of antibiotic in the anterior chamber, compared with those who had received the antibiotic just for 1 day and for 3 days.

“Not only is the antibiotic sitting in the anterior chamber, but it’s now diffused into the ciliary body, iris and cornea, so we have higher concentrations of antibiotic before we start,” Dr. Roberts said.

In his own practice, Dr. Roberts has his patients using topical NSAIDs for 3 days prior to surgery.

Dr. Roberts gives each patient a preprinted prescription for Acular PF (ketorolac tromethamine; Allergan) and Ocuflox (ofloxacin; Allergan) four times per day for the 3 days prior to surgery.

When they arrive at the surgery center, they continue Acular, Ocuflox and dilating drops. They continue that in the recovery room and for 1 week. Then they stop their steroids and antibiotics and just continue with their nonsteroidals for 1 month.

“Despite the fact that we don’t have a perfect rationale for using preoperative antibiotics, we should have the best data that we can for how we are going to dose them,” Dr. Roberts said. “At least in my hands and based on the results of the study I performed, I feel confident that to start the patient 3 days prior to surgery is the most efficacious way of antibiotic prophylaxis.”

Postoperative care

The choice among quinolones has been one of the most fiercely fought contests in recent years, with Allergan and Alcon promoting the properties of their respective drugs.

Harold R. Katz, MD, designed a study to determine if ciprofloxacin (Ciloxan; Alcon) or ofloxacin is more effective in reducing bacterial flora on the ocular surface of human subjects 55 years and older. The results of this study were presented at the ASCRS and Association for Research in Vision and Ophthalmology meetings this year.

He designed a prospective, unmasked, nonrandomized comparative study designed to simulate surgical prophylaxis. Human volunteers were assigned to one of three study arms. Each study arm had 20 eyes. The control group was untreated, followed by a ciprofloxacin group and an ofloxacin group.

Researchers performed a pretreatment conjunctival culture. In order for a patient to be entered into this study, they had to have at least 50 colony-forming units from that initial conjunctival culture.

Each of the two treatment groups received one drop of antibiotic every 5 minutes. They were cultured before application of the antibiotic drops. The culture was repeated at 15 minutes, 30 minutes, 1 hour and 2 hours after instillation of the last drop. The control group was cultured at corresponding time points. Colony counts were performed after incubating the culture plates for 48 hours.

“Initially, there’s a little bit of a drop in colony counts in the control group and then it goes back up again,” Dr. Katz said. “Probably what was happening was just mechanically culturing the ocular surface actually reduced the number of organisms, and then they entered into a log growth phase and increased back up again.”

The ofloxacin group experienced no statistically significant difference from control until it reached the 2-hour time point. The relatively slow effect of ofloxacin in reducing colony counts is consistent with in vitro kill curve data, Dr. Katz said.

The ciprofloxacin group experienced a 98% reduction in the ocular surface flora at 15 minutes and that reduction was present at every time point. It was highly statistically significant, compared with the control, Dr. Katz said.

“When we compared the ciprofloxacin with the ofloxacin group, there was a dramatic difference between the two groups at every time point, and the difference was highly statistically significant at every time point,” Dr. Katz said. “Ciprofloxacin reduces the ocular surface flora on the human conjunctiva more effectively than ofloxacin for at least a 2-hour period after instillation of three drops of antibiotic.”

Most effective use

Researchers are not only choosing particular combinations of quinolones but are attempting to find the most effective methods of application.

Eric D. Donnenfeld, MD, Henry D. Perry, MD, and Robert W. Snyder, MD, PhD, have conducted research into the penetration of quinolones into deeper stromal tissues. They attempt to dehydrate the cornea and then add quinolones, so that the stromal pump action pulls the drugs more deeply into corneal tissue.

They dehydrated the corneas of 30 rabbits. After 2 minutes, they rehydrated the tissue with either four drops of Ciloxan, four drops of Ocuflox or four drops of Tobrex (tobramycin; Alcon). The controls were hydrated with balanced salt solution, and then 1 minute later they were given the four drops of Ciloxan, Ocuflox or Tobrex.

An hour later, the corneas were excised and digested. They assayed the corneal tissue and found that in the hydrated state, they had better penetration again with Ocuflox than with ciprofloxacin.

“The cornea can act as a therapeutic sponge,” Dr. Snyder said. “The rehydrating of the cornea with the fluoroquinolone after it has been placed under the operating microscope significantly increases the antibiotic delivery in the corneal tissue.”

For Your Information:

• Robert M. Kershner, MD, can be reached at the Orange Grove Eye Surgery Center, 1925 W. Orange Grove Road, Ste. 303, Tuscon, AZ 85704-1152; (520) 797-2020; fax: (520) 797-2235. Dr. Kershner has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Kerry D. Solomon, MD, can be reached at the Storm Eye Institute, 171 Ashley Ave., Charleston, SC 29425; (843) 792-8854; fax: (843) 792-6347. Dr. Solomon has no direct financial interest in any of the products mentioned in this article. He is a paid consultant for Allergan Pharmaceuticals.
• Calvin W. Roberts, MD, can be reached at 520 E. 70th St., Ste. Starr 817, New York, NY 10021-9800; (212) 734-7788; fax: (212) 734-4476. Dr. Roberts has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Harold R. Katz, MD, practices at Sinai Hospital of Baltimore, 2411 W. Belvedere Ave., Baltimore, MD 21215; (410) 578-5991; fax: (410) 578-6284. Dr. Katz has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Robert W. Snyder, MD, PhD, practices at 1801 N. Campbell Ave., Tucson, AZ 85719; (520) 321-3677; fax: (520) 321-3665. Dr. Snyder did not disclose whether or not he has a direct financial interest in any of the products mentioned in this article or if he is a paid consultant for any companies mentioned.