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Does Increased IOP during Femtosecond LASIK Matter?  
By Linda Roach

Since the early days of LASIK, some ophthalmologists have expressed concern about possible ocular damage from high intraocular pressure (IOP) when mechanical microkeratomes cut LASIK flaps. Today, this same issue is being raised with the femtosecond laser. 

A study recently published online ahead of print by the Journal of Refractive Surgery (JRS) suggests that IOP can spike dramatically during treatment with some femtosecond laser systems, shutting off the eye's blood supply for one minute or longer.1

"If you have a procedure where you do a very hard applanation and increase the IOP a great deal, and then you continue with the treatment without taking care of the IOP, then you might have that extremely high IOP during the entire procedure," said Jan M. Vetter, MD, the lead author of the study and director of the Eye Bank at Johannes-Gutenberg University School of Medicine in Mainz, Germany.

No Link to Ocular Damage
Although the IOP levels Dr. Vetter and his colleagues found were dramatic, this lengthy cutoff of circulation has not been linked to damage to the two ocular structures vulnerable to ischemic damage: the optic nerve and the choroid. Furthermore, ophthalmologists have not seen a spate of posterior segment complications that occur with high pressure, such as posterior vitreous detachment, rhegmatogenous retinal detachment, macular hemorrhage and macular holes.

The blood supply to the eye is cut off when IOP exceeds approximately 60 mmHg, a level exceeded during flap construction with both conventional microkeratomes and femtosecond lasers. A study published in 2007 in the American Journal of Ophthalmology found indications that high IOP was indeed cutting off blood flow in LASIK eyes.2

The authors reported that a microkeratome (Zyoptix XP, Bausch+Lomb) caused loss of all light perception in 85 percent of LASIK patients during the suction vacuum step and in 90 percent during flap cutting. The respective figures from the JRS study were 39 percent and 61 percent during flap preparation with the leading femtosecond laser (IntraLase, Abbott Medical Optics).

However, clinical experience with millions of LASIK surgeries would seem to indicate that these temporary cutoffs in ocular blood flow do not seem to harm the eye, Dr. Vetter said.

"Is there a medium-term or long-term problem from this? Most likely only in very, very few cases," he said. "But these high pressures still are something that might be harmful and which should be avoided if possible."

Living Eye Might Protect Itself
There may be an autoregulatory response within the living human eye that compensates for the temporary loss of blood flow, said Harry A. Quigley, MD, a noted glaucoma expert and the Maumenee Professor of Ophthalmology at Johns Hopkins University. But the high IOP readings during flap preparation are still worrisome, he said. 

"This was going on with blade LASIK, too. We all worried about it," Dr. Quigley said. "If somebody could invent a way to do LASIK that did not raise IOP in this way,that would be a good thing. And I would be glad to see that happen."

In the meantime, if the goal is to keep IOP as low as possible during femtosecond LASIK, the JRS study suggests that not all laser systems are created equal. The study's authors compared results with the 60 kHz IntraLase (Abbott Medical Optics, Abbott Park, Ill.), 200 kHz VisuMax (Carl Zeiss Meditec AG, Jena, Germany), Femtec (Technolas Perfect Vision, Heidelberg, Germany) and Femto LDV (Ziemer Ophthalmic Systems AG, Port, Switzerland).They found stark differences among the femtosecond lasers in how high IOP climbed and for how long.   

IOP Spikes as Docking Begins
With all of the lasers, IOP spiked immediately when the docking ring or cone was placed onto the cornea, with high IOP continuing until it was detached. At touchdown, mean pressure in the eyes immediately rose by 23 to 51 mmHg to at least double baseline IOP.

The lowest initial increase was with the Femtec, at 23 ± 11 mmHg. But as the procedure continued, this pressure advantage was wiped out by rapidly rising IOP, with the highest peak IOPs among the devices seen with the Femtec (mean 205 ± 32 mmHg).

The VisuMax performed better at preventing any further large increases beyond the initial spike. After rising by 47 ± 22 mmHg at touchdown, IOP in the eyes treated with the VisuMax eased slightly as the system automatically adjusted the docking apparatus. IOP hovered around approximately 40 to 50 mmHg as the flap creation proceeded, peaking at a mean of 65 ± 20 mmHg.  

In eyes treated by the other three lasers, however, further large jumps in IOP occurred as the flap procedure progressed.

IOP Maximum Tops 100 with Three Lasers
The mean maximum IOP during normal flap preparation exceeded 100 mmHg with three of the lasers, with the Femtec producing IOP readings twice that. The mean peak IOP figures for the lasers, in order of increasing maximum IOP, were 65 ± 20 mmHg (range, 37 to 93) with the VisuMax, 135 ± 16 (range, 109 to 161) with the IntraLase, 184 ± 28 (range, 142 to 218) with the Femto LDV and 205 ± 32 (range, 161 to 262) with the Femtec.  

The study was conducted using an IOP measurement method described in a study published in the Journal of Cataract & Refractive Surgery in 2007.3 A pressure transducer (33X; Keller, Jestetten, Germany) was assembled and calibrated and then connected to an infusion set and to a transparent chamber with a 20-gauge cannulation needle on top. The cannulation needle was inserted through the optic nerve and into the vitreous cavity of each globe. IOP was measured every 100 milliseconds during flap creation.

Segmented Ring Might Be an Advantage
Variations in the designs of the suction rings and in the applanating plates appear to be responsible for the different IOP levels induced during flap making, Dr. Vetter said.

He explained that the 200 kHz VisuMax used in the study has a segmented ring that apparently moderated IOP changes by preventing excess tissue displacement during suction. This system also has a curved, concave contact plate that the authors credit for moderating pressure during eye docking. (In contrast, the IntraLase has a smooth ring and flat applanation plate.) However, average peak IOP in the study was highest with the Femtec laser even though it, too, has a curved, cone-shaped applanation apparatus.

This is one of several weaknesses in the study that Perry S. Binder, MD, a leading U.S. femtosecond LASIK surgeon, pointed out in an article appearing in Refractive Surgery Outlook. Dr. Binder is the medical monitor for AMO/IntraLase and lectures regularly about the characteristics and capabilities of all ophthalmic femtosecond lasers.

Curved or Flat Applanation?
"The authors suggested that the curved cone of the VisuMax laser was responsible for the lower pressures with that laser, but then they got high pressures with the other laser that uses a curved cone," Dr. Binder said. "So in their model, the absence of a cone shape does not correlate with increased IOP."

Manufacturers typically emphasize the speed with which their laser cuts the flap, but this stage typically accounted for at most half of the total time during which IOP stayed high (the suction and cutting phases), the researchers found. The following table lists the mean lengths for these steps in the study.  

Dr. Binder questioned the validity of these and other figures in the paper, as well as the applicability of the results to today's improved lasers. His specific criticisms include: 

• The study involved only porcine eyes (n=48). "Pig models are the best we have, other than human eyes from an eye bank, but we can't really correlate the results of a study in pig eyes to human eyes." 
• The surgeons' experience with the different laser models could have lengthened the suction and cutting phases. "They may have taken longer to do the procedure and they may have pushed harder on the globe, and this would have affected the IOP." 
• The lengthy cutting times also may reflect variations in flap size and in the spot size and spacing chosen. "They didn't give us any of those settings in the paper, so that we can compare apples and oranges. Without knowing the settings you can't really come to conclusions about the validity of the comparisons. Tighter spot and line settings and smaller flap diameters all affect procedure times."
• The study was conducted with femtosecond laser systems that pulsed much more slowly than do  models available today. The IntraLase repetition rate has nearly doubled to 150 kHz; the VisuMax rate is 500 kHz, compared to 200 kHz in the earlier model.  

New Models Work Faster
"Based on my experience with the FD 60 laser, my suction and laser times are much shorter than theirs," Dr. Binder said. "This reinforces my assessment that the experience of the surgeons, combined with the laser settings they were using, led to the longer procedure times they reported."

Dr. Binder recalled that, with a normal spot size, he could cut a 9 mm LASIK flap in 17 seconds with the IntraLase FS90, the model used in the study. The researchers reported a mean of 36 ± 6 seconds. His suction phase lasted for about 30 seconds, less than a third as long as the study average.

"What has happened is that the laser delivery speeds are faster with all femtosecond lasers. Therefore, better lasers and better surgeon experience are leading to much shorter procedure times and a reduction of the eye's exposure to elevated IOP," Dr. Binder said. 

In their study, Vetter and colleagues also simulated "worst-case" procedures, by extending the usual docking maneuver until the laser system automatically aborted the flap procedure or warned the user of excessive applanation pressure.

These "worst-case" procedures are indicative of how high IOP might rise at the beginning of a surgeon's femto-learning curve, they said. "In the hands of an inexperienced surgeon, user-dependent peak IOP up to 300 mmHg is possible," they wrote.

Consequently, surgeons should not ignore the laser's automatic warnings, especially if they are new to femtosecond LASIK, Dr. Vetter said.

"It is important that a surgeon get a good introduction to what pressure is necessary and sufficient to achieve a good cut," he said. "Surgeons also should be aware of how high the potential IOP could be and should begin to be more cautious when they see a yellow warning light."

Optic Nerve and Choroid May be at Risk
Dr. Quigley, the glaucoma expert, is concerned that lack of blood flow at any IOP level above approximately 60 mmHg puts the oxygen-hungry optic nerve and the choroid at risk for damage.

However, he and Dr. Binder are reassured by the many millions of LASIK procedures that already have been performed worldwide.

"If IOP were an issue, we would have seen more central retinal artery occlusions, and we would have seen more of the posterior segment complications that the authors talked about in their study," Dr. Binder said.

"If this was having some sort of short- or medium-term effect, we probably would have seen it by now," Dr. Quigley said. "We probably would see a whole lot of people who have undergone LASIK who have some detectable loss in their field of vision several years after the surgery."

However, this reassuring picture remains hazy. No one really knows if subtle, undetected visual deficits occur in LASIK patients years after surgery because no one has looked specifically for them, he said.

"I don't think there have been any long- or short-term studies comparing the ERGs [electroretinograms] of LASIK patients five years after surgery to the ERGs of non-LASIK patients," Dr. Quigley said. "That would be the study to do."

References
1. Vetter JM, Holzer MP, Teping C, et al. Intraocular Pressure During Corneal Flap Preparation: Comparison Among Four Femtosecond Lasers in Porcine Eyes. J Refract Surg. Dec. 15, 2010 [Epub ahead of print].
2. Tan CS, Au Eong KG, Lee HM. Visual experiences during different stages of LASIK: Zyoptix XP microkeratome vs Intralase femtosecond laser. Am J Ophthalmol. 2007;143(1):90-96.
3. Bradley JC, McCartney DL, Craenen GA. Continuous intraocular pressure recordings during lamellar microkeratotomy of enucleated human eyes. J Cataract Refract Surg. 2007;33(5):869-872.

Financial Interest Disclosures
Drs. Vetter and Quigley have no conflicts of interest to disclose.
Dr. Binder is medical monitor for IntraLase.