ARVO brings news of glaucoma drugs, anti-infectives

New fluoroquinolones cover organisms that showed resistance to earlier compounds.

Issue: July 1, 2001

FORT LAUDERDALE, Fla. — Data on the latest pharmaceuticals, from new fluoroquinolones to glaucoma medications, and on research topics from choroidal neovascularization to nerve fiber layer assessment, were presented here at the annual meeting of the Association for Research and Vision in Ophthalmology.

New anti-infectives received much attention, with 4th-generation fluoroquinolones such as moxifloxacin and gatifloxacin demonstrating coverage of organisms that have shown resistance to earlier-generation fluoroquinolones.

Presentations on the new glaucoma drugs derived from prostaglandins and related compounds such as prosta mides considered their effects on blood flow as well as their intraocular pressure-lowering properties.

New fluoroquinolones

In the field of anti-infectives, an in vitro study comparing 2nd-, 3rd- and 4th-generation fluoroquinolones found that 4th-generation fluoroquinolones are more potent than 2nd- and 3rd-generation fluoroquinolones for gram-positive organisms, and are equally potent for gram-negative organisms.

The in vitro study also concluded that 4th-generation fluoroquinolones appear to cover strains resistant to 2nd- and 3rd-generation fluoroquinolones. In this study, moxifloxacin was generally more potent than gatifloxacin for gram-positive bacteria.

Researchers R. Mather, R.P. Kowalski and associates from the Charles T. Campbell Laboratory at the University of Pittsburgh conducted a study comparing the potency of 2nd-generation fluoroquinolones (ciprofloxacin and ofloxacin) with 3rd-generation (levofloxacin) and 4th-generation fluoroquinolones (gatifloxacin and moxifloxacin).

Frozen stocks of 98 bacterial isolates from endophthalmitis cases were used. The minimum inhibitory concentration (MIC; µg/mL) of the isolates was determined using E-tests. The MICs were analyzed nonparametrically as discrete data (by Epistat, of Richardson, Texas). The analysis ranked all the MICs from lowest to highest and compared the antibiotics by analysis of variance (ANOVA) of the ranks (not the actual MICs) using Duncan’s multiple comparisons (P = 0.05 significance). The lower the median MIC, the better the drug’s potency.

The researchers said the 4th-generation fluoroquinolones may represent an option, or adjunct, in surgical prophylaxis in the treatment of bacterial endophthalmitis. They said clinical studies will be necessary to correlate the in vitro results.

Effective against Staph

In another study involving quinolones, moxifloxacin was found to be highly active against quinolone-resistant isolates of Staphylococcus aureus and S epidermidis, as well as quinolone-susceptible isolates.

“It’s eight to 32 times more active against Staph species and strep,” said David W. Stroman, MD. “The issue in Staph that you see is quinolone resistance. Is this going to be active enough to be effective? The answer is yes.”

The drug is still in clinical trials.

Travoprost in black patients

Travoprost 0.004% lowers intraocular pressure (IOP) significantly better in blacks than in non-blacks, according to data presented here. It also lowers IOP significantly better in black patients than timolol or latanoprost, and a greater percentage of black patients respond to travoprost 0.004% than to latanoprost or timolol.

E.K. Sullivan, MD, and Michael V.W. Bergamini, MD, discussed results garnered from three pivotal and two dose-response studies. Travoprost 0.004% was found to be more effective than timolol in lowering IOP, by up to 3.2 mm Hg. In addition, there was a significantly greater reduction in mean IOP in blacks in the travoprost 0.004% group than in the latanoprost group, and there was no significant difference between groups in non-black patients.

Data combined across the dose-response studies demonstrated a significantly lower mean IOP in black patients following treatment with travoprost 0.004% compared to travoprost 0.0015%. In addition, mean IOP following treatment with travoprost 0.004% was significantly lower in blacks than in non-blacks.

Drs. Sullivan and Bergamini told Ocular Surgery News that “many” more studies on the topic are currently under way.

Unoprostone and blood flow

Topical unoprostone significantly increases ocular blood flow and maintains the effect for at least 6 months in normal tension glaucoma patients, according to a study.

I. Kimura, MD, T. Tanino, MD, Y. Ohtake, MD, and Y. Mashima, MD, of Keio University School of Medicine in Tokyo, conducted a study to evaluate the effect of topical isopropyl unoprostone on tissue circulation in the optic nerve head and juxtapapillary retina in normal tension glaucoma patients. Eleven right eyes of seven males and four females between the ages of 37 and 74 were studied.

Blood flow measurements were performed with the Heidelberg Retina Flowmeter before use of the medication and 3 and 6 months after starting the medication. IOP was also recorded at each point. Patients were to instill 30 µL of unoprostone (0.12%) twice daily. Five images suitable for blood flow measurements of each area were selected, and the averages of the measurements of the three images except the largest and smallest values were used for statistical analysis.

The mean flow values of all analyzed areas except for superonasal and temporal juxtapapillary retina increased at 6 months when compared with baseline values. IOP did not show significant change, according to the study.

Latanoprost and blood flow

In healthy individuals, the IOP reduction after treatment with latano prost is associated with unchanged retrobulbar hemodynamics and mean retinal capillary flow, according to a study. However, the authors indicate that latanoprost does increase retinal capillary areas of zero flow, suggesting that prostaglandin F alters retinal patterns of capillary recruitment.

T.J. Steffens, MD, A. Harris, MD, and L. Kagemann, MD, of Indiana University Department of Ophthalmology conducted a study to determine how latanoprost, a prostaglandin F analogue, affects IOP, retrobulbar hemodynamics and retinal capillary perfusion in healthy adults. Twelve people with refractive errors between –6 D and +2 D, with astigmatism of less than 1.5 D, received latanoprost or a placebo once daily for 4 weeks in a double-masked crossover design. Color Doppler imaging determined flow velocities in four retrobulbar arteries. Retinal capillary per fusion in the superior and inferior temp oral retina was determined using con focal scanning laser Doppler flowmetry.

IOP was significantly reduced using latanoprost as compared to placebo. Latanoprost significantly reduced flow in the superior temporal peripapillary retina, according to the study. Latanoprost demonstrated a significant increase in zero-flow pixels in the temporary peripapillary area. It eliminated the significant difference in zero-flow pixels between the inferior and superior temporal peripapillary areas. There were no drug effects on blood pressure, heart rate, visual acuity or contrast sensitivity, the authors indicated.

Feeder vessel treatment in CNV

Treatment of feeder vessels in fibrovascular choroidal neovascularization (CNV) can close the vessels to decrease or eliminate leakage and improve visual acuity.

According to Robert P. Murphy, MD, feeder vessel treatment can improve eyes with long-standing subfoveal fibrovascular CNV in age-related macular degeneration.

“Eyes we thought had no recoverable vision often did,” he said.

In a consecutive series of treatments of CNV in 19 eyes of 17 patients, leakage resolved in 14 cases (74%) and decreased in five (26%).

Nerve fiber layer after LASIK

On the surgical front, one study concluded that changes that occur in retinal nerve fiber layer thickness (RNFL) after LASIK are not directly related to the effects of the refractive procedure.

According to Rabia Gurses-Ozdin, MD, even though there were slight differences in scanning laser polarimetry (SLP), there was not enough data to conclude that RNFL damage was caused by LASIK.

“Nobody knows if this affects the eye or not,” Dr. Gurses-Ozdin said. “Everybody is curious if this is affecting the nerve fiber layer or not.”

According to Dr. Gurses-Ozdin, alterations in RNFL thickness measurements seen on SLP are due to alterations in corneal architecture and polarization rather than actual LASIK-induced change.

Algorithm for OCT

A new algorithm developed by Ohio State University has produced superior results to the Humphrey algorithm for use with optical coherence tomography (OCT).

“It would please me if it was used by other researchers to use the OCT as a more practical tool,” said Dara Koozekanani, MS, a PhD candidate at Ohio State University. “This enhances the usability of the OCT. You have less failure than the Humphrey algorithm.”

Her study analyzed 467 OCT scans on 26 normal eyes, using both the Humphrey algorithm and the Ohio State algorithm. Quantitatively, the error rate values were superior to those of the Humphrey algorithm. “I think it uses a more complicated mathematical model,” Mr. Koozekanani said.