When a virus invades your system and no vaccine is available, often the only option is to ride it out and treat the symptoms as best you can. Similarly, most of the treatments currently used in response to presbyopia, such as monovision or multifocal intraocular lenses, though effective, only treat the “symptoms” by optically compensating for the loss of accommodation. For several years now, physicians have worked on reversing presbyopia through surgical means, but haven’t perfected a technique. In this article, Review looks at several of the procedures in the works to see what obstacles stand in the way of the procedures producing consistent, predictable results.

Scleral Expansion Inserts
This procedure, in which four inserts are placed in quadrants in the sclera above the ciliary muscle, was invented by Houston surgeon Ronald Schachar in the early 1990s. It operates under Dr. Schachar’s own theory of accommodation and presbyopia, which differs from the traditionally recognized mechanism described by the German physicist Hermann Helmholtz more than 100 years ago. The segments, in theory, give the muscle more working space with which to change the lens’ shape and accommodate.

In the FDA study of the surgical reversal of presbyopia, the SRP inserts achieved an average of 1.7 D of accommodation.

In Helmholtz’s theory, when the eye isn’t accommodating, there is a resting zonular tension at the lens equator which keeps the equator pulled outward, toward the sclera, and the lens relatively flat. It’s in this state that the eye can see distant objects. The theory suggests that, with accommodation, the ciliary muscle contracts and its apex moves away from the sclera toward the lens equator, releasing the zonular tension. The elastic nature of the capsular bag then allows the lens to be molded into a more spherical shape that increases the eye’s optical power, allowing it to focus on things up close.

Schachar’s theory describes almost the opposite action. Dr. Schachar theorizes that, when the lens accommodates, zonular tension at the lens equator is increased, not released. This increase, the theory states, pulls the lens equator out toward the sclera, resulting in a flattening of the peripheral surface of the lens but an increase in the curvature of the central region that allows accommodation. Dr. Schachar postulates that presbyopia results from the lens growing in size as it ages until it crowds the ciliary muscle, and the muscle can no longer work properly.

Some in the research community, however, think surgeons who base any type of presbyopia reversal surgery on a theory other than Helmholtz’s may be headed for a disappointment.

“In my mind, I’m not sure that presbyopia reversal surgery will ever be ready for general distribution,” says Adrian Glasser, PhD, of the University of Houston. “What we know and understand about the causes of presbyopia is that the human crystalline lens gradually loses its ability to undergo accommodative changes with increasing age.” He says the hardening of the lens is most likely the primary culprit.

“In a young eye, the crystalline lens is relatively soft and malleable, able to undergo accommodative change,” he says. “But, with increasing age, the lens simply becomes too hard.”

To illustrate the point that presbyopia reversal procedures should at least operate under the Helmholtz theory, Dr. Glasser points to a study he performed in 1999.¹ In it, he and his co-workers tried to see if the lens equator in rhesus monkeys moved away from the sclera under accommodation as Helmholtz claimed, or toward it, as Dr. Schachar theorizes.

“All of the experiments we performed demonstrated the same thing, namely that, when the monkey accommodated, the lens equator moved away from the sclera,” he says.

That said, a certain number of patients who receive scleral expansion segments, a procedure now referred to as the surgical reversal of presbyopia and developed by Presby Corp. (Dallas) and CIBA Vision, do regain the ability to read. Whether the theory the procedure operates under is correct or not, these successes keep surgeons coming back to work with and tweak the procedure, which is now in a U.S. Food and Drug Administration trial.

In the current FDA Phase I study of SRP, the average improvement in accommodative amplitude was 1.7 D, but about half of the patients got no effect. Houston surgeon Warren Cross has studied the procedure in 120 eyes. He says, though, that a small number of them got as much as 7 D of accommodative amplitude. (For an update on the FDA trial of SRP, see the feature on pg. 32). As it’s currently performed, however, the procedure doesn’t appear to be a slam-dunk, and complications can occur, including:

•  Anterior segment ischemia. Out of 120 eyes he’s studied, Dr. Cross has seen this once. Incorrectly placing the segments over the ocular blood supply rather than the ciliary muscles can choke off circulation.

•  Segments in the suprachoroidal space. “This doesn’t cause detachment or hemorrhage but can cause a great deal of agitation when you lose a segment that you can’t get out,” says Dr. Cross. It can take up to six months to repair. This has occurred in 10 of Dr. Cross’ 120 patients.

•  Hyperopic shift. Dr. Cross says that, in the accommodating hyperope, who is the type of patient most likely to undergo the procedure, the refraction can drift 1 D to 1.5 D into hyperopia postop. This has necessitated performing a hyperopic PRK or LASIK on these patients about six months after their SRP procedure.

• Induced astigmatism. Dr. Cross says SRP can temporarily induce as much as 3.5 D of cylinder for up to four months.

•  Nausea. Because the procedure pulls on the ciliary body, about a third of patients experience nausea and brow ache for about four to six hours postop. A quarter may actually vomit.

Though it’s not a complication, the procedure can also be time-consuming. “The quickest we’ve done took 40 minutes for two eyes,” says Dr. Cross. “For a patient with bad exposure, such as tiny lid openings, deep-set eyes, small orbits and lots of orbital fat, it can take up to an hour and a half.”

In an effort to make the procedure easier by standardizing the incision in which the segments are placed, Presby Corp. has developed an automated device called the Focal 1. When Dr. Cross tried the device though, he says “the blades weren’t sharp enough to work well,” so he still uses a diamond blade. If Presby Corp. can get the device configured correctly, however, he ventures to say that “it would be a procedure for almost any ophthalmologist.”

Anterior Ciliary Sclerotomy
ACS is a procedure that makes incisions in the same general area of the sclera over the ciliary body in which SRP’s segments are implanted. When done with a knife, though, it only allows patients to see near objects for about two weeks, then the effect disappears.

More than a year ago, Los Angeles refractive surgeon Robert Maloney undertook a prospective study of ACS in 60 eyes.² The study was cut short, however, after only nine eyes had undergone the procedure.

“No patient had any improvement in accommodative amplitude, and two eyes had potentially serious complications,” says Dr. Maloney. “One was a perforation and the other was a mild case of anterior segment ischemia. The procedure is totally ineffective and dangerous.”

Atlanta surgeon James Hays, who’s personally sponsoring a study of a different kind of ACS that uses implanted barrier segments to hold the incisions open, takes issue with the study. “I don’t know what operation they were doing,” he says, “but they never came to us and said, ‘How are you doing this operation?’ We’ve had no anterior segment ischemia at all.”

Inserting these segments in the wounds as Dr. Hays is doing, or using a laser to create the incisions as is done with the SurgiLight OptiVision system (SurgiLight, Orlando, Fla.), may stave off the effect’s regression. Both are in the initial stages of gathering solid data, though.

Dr. Hays says that, in the 67 patients that his group has done abroad, there has been a “really modest” effect on accommodative amplitude, with no one getting more than 2 D. Even so, a number of the patients can still read. “The accommodative amplitude we get doesn’t seem to reflect the ability to read at near,” he says. “It may have something to do with strengthening the muscle with use.” He believes they need an objective way to measure how much accommodation the patients are getting. To this end, he recently purchased a Tracey Visual Function Analyzer (Tracey Technologies, Houston), and expects that to give him a more definitive answer.

Also, half of the small barriers the surgeons put into each of the four radial incisions in the sclera have extruded. To combat this, Dr. Hays has redesigned the barriers.

Though it would seem that ACS with barriers is the same as SRP, Dr. Hays vows that it isn’t. “SRP is pulling the sclera open; this is just a passive expansion with incisions that lets the intraocular pressure and the relaxation of the eye wall cause a passive expansion. We were thinking that anything that pulls on the sclera will eventually stretch and lose effect.”

Though the procedure is in the early stages and has what Dr. Hays describes as “relatively poor hard number data follow-up,” he is still excited enough by some of the results to continue to work on it. “Having the aberrometers will really tell us if we’re getting the results we think we’re getting,” he says.

The other variation on ACS under evaluation outside of the United States involves making scleral incisions with the SurgiLight OptiVision laser. According to Colette Cozean, PhD, SurgiLight’s CEO, the idea is to use a laser to make the incisions with the hope that the thermal effect of the laser will delay ingrowth, allowing fibrin to fill the fissure and make the cut permanent. She can’t say for sure the mechanism behind its effects, though.

“I wish I could [explain the mechanism],” she says. “I can tell you this: There are pieces of Schachar’s and Helmholtz’s theories that seem to be true and pieces that seem to be false. There appears to be more things at work, as some patients go from J16 to J2 with only a few diopters of accommodation.”

At this point, without all the data processed from around 300 eyes, Dr. Cozean estimates the average amplitude of accommodation recovered by patients as measured by the push-up method, blur and with dynamic retinoscopy to be 2 D, though some results have been as high as 8 D and as low as 1 D. Six patients have had no effect and one patient had his effect regress after six months. “Most of the complaints we get are dry eyes and conjunctival hemorrhaging for one to seven days,” she says. There have been four microperforations that resolved in a week. She says that the procedure weakens the globe but at a level that’s “much less than what was done with RK.” The company is now just waiting to see if patients’ vision changes with longer follow-up. “We’re not changing anything at this point and haven’t changed anything for over a year and a half,” she says.

The Intraocular Route
In patients with cataracts, surgeons are exploring accommodative intraocular lenses. Dr. Glasser thinks that manipulating the lens itself may be the answer to consistent presbyopia reversal, since doing so respects Helmholtz’s theory of accommodation.

IOLs such as the HumanOptics 1CU lens (above) and the CrystaLens may restore accommodation intraocularly.

“If accommodation is to be restored,” he says, “the appropriate thing to do is to replace the human cataractous crystalline lens with a lens that can undergo accommodative changes,” he says.

To this end, the lens furthest along the clinical trial path in the United States is the CrystaLens from C and C Vision (Aliso Viejo, Calif.), which has submitted its final phase data to the FDA. The other major accommodative IOL is the 1CU from HumanOptics (Erlangen, Germany), which is only for sale outside of the United States.
The CrystaLens is a three-piece modified plate silicone device that employs hinges between the haptics and the optic to facilitate the lens’s movement in the eye that allows patients to read. In its U.S. FDA study, the lens’s powers range from +16 D to +23 D.

According to Houston surgeon Steve Slade, medical monitor for the CrystaLens’s U.S. study, there is a generally agreed-upon mechanism behind the lens. “As a result of the ciliary muscles contracting, the zonules are released, allowing vitreous pressure to move the lens forward,” he says.

Though the company won’t share exact outcomes data while the FDA reviews its submission, Dr. Slade says that, in bilateral implantations, around 90-plus percent of patients see J3 at near and 20/30 at distance.

The HumanOptics lens has been used in Europe for a little over two years, and has been implanted in 7,500 eyes. Thomas Homscheid, corporate communications manager for HumanOptics, says the results with the lens are “encouraging,” producing a modest amount of average accommodative amplitude, 1.2 to 1.5 D.

A third intraocular modality that’s in the earliest of stages is the SmartLens from Medennium (Irvine, Calif.). Eugene, Ore., surgeon I. Howard Fine is the principal investigator for the lens.

“It’s hydrophobic acrylic that can be made into a full- size lens that fills the capsular bag,” Dr. Fine says, speculating on the lens’s properties. “As a result, there won’t be any decentration, edge effects, glare or spherical aberration and it can have any dioptric power you want imprinted on it.” He says that, once the lens is created, it can be made into a stable, 2-mm rod at room temperature that can be inserted through a very small incision. At body temperature in the capsular bag, it should return to its original shape and dioptric power. Because it’s flexible, it may be capable of accommodation. The lens hasn’t been implanted in vivo yet, only in water that’s at body temperature. Optical bench testing and animal studies are next.

At this stage of the evolution of presbyopic reversal surgery, there is no clear-cut winner that can produce ample amounts of accommodation as consistently, predictably and safely as phaco can produce 20/25 patients. Only the future will tell if such a procedure will emerge.

“I don’t think any presbyopia surgery will be as good as phaco is now,” says Dr. Hays. “Because presbyopia is dependent on muscle function so much. I don’t think it will ever get that predictable. It won’t make a 70-year-old read J2.” 

1. Glasser A, Kaufman P. The mechanism of accommodation in primates. Ophthalmology 1999;106:5:863-72.
2. Hamilton DR, Davidorf JM, Maloney RK. Anterior ciliary sclerotomy for treatment of presbyopia: A prospective controlled study. Ophthalmology 2002;109:11:1970-6.