Read Refractive Surgery Outlook
Three new paradigms in surgical vision correction
By Linda Roach
Clinical trial results for three new technologies suggest that each shows potential for addressing the visual problems of patients who largely have been left out of the refractive surgery revolution -- low myopes, low hyperopes and emmetropes in their early forties with presbyopia.
People with up to 2 D of refractive error generally do not seek out LASIK or PRK treatment because the risks of surgery outweigh the potential benefits. Although excimer laser techniques are available to reduce symptoms of presbyopia, they require visual compromises that emmetropes are reluctant to make.
Keraflex may treat keratoconus, post-LASIK ectasia
Developed as a form of thermal keratoplasty to correct myopia, Keraflex is now under investigation as a treatment for keratoconus and post-LASIK ectasia. The treatment flattens the cornea, changing its refractive power, but does not remove any tissue.
Two electrodes deliver a pulse of microwave energy in annular patterns in the midperipheral cornea. The amount of refractive correction is controlled by varying ring diameters and other parameters.
One brief microwave pulse
The microwave pulse lasts less than a second. A proprietary system of evaporative cooling during the pulse prevents thermal damage to Bowman’s membrane. The result is two rings of shrunken collagen in the midperipheral stroma. Biomechanical force from the stiffened tissue pulls on the central cornea, flattening it.
This incisionless procedure improves distance visual acuity without weakening the cornea’s structural integrity and without triggering a wound healing response, said David Muller, PhD, president and CEO of Avedro, Inc. (Waltham, Mass.), the makers of Keraflex. He adds that in trials and clinical use, there have been no reports of complications.
Cooling the surface is key
“We cool the corneal surface during the procedure, so you don’t end up with any residual scarring. The keratocytes are not activated,” Muller said. “There is a temporary epithelial defect a couple hundred microns wide, and that heals up by that evening.”
But, as with previous unsuccessful attempts at heating the cornea to change refractive power, the company’s initial trials showed that the effect disappeared within a few months. More recent trials addressed this problem with collagen cross-linking, but only in the annular areas affected by the thermokeratoplasty.
“Looking at low myopes, we’re seeing good stability at six months postop,” Muller said. “We feel very confident with the procedure in its predictability and stability.”
The cross-linking can be performed separately from the microwave treatment, which patients who are leery of refractive surgery will find reassuring, Muller said.
“The cross-linking does not have to be done at the same time as the cornea flattening. This takes a little bit of the pressure off the surgeon, as well as the patient, because if the patient doesn’t like their refractive results, you can let them drift into emmetropia,” he said.
But even with cross-linking, the refractive effect is not permanent. “We tell patients that their improved vision will last about 18 months, and they can expect to come in to have the procedure repeated,” Muller said. “We feel and I think the patients feel that if the effect lasts for a year or two and you have to do it again — well, it’s just a 30-second procedure,” he said.
Already in use internationally
Avedro's microwave-emitting device used for Keraflex, the Vedera KXS, already has the European CE mark for therapeutic cross-linking treatments. It is being used by corneal surgeons in many countries outside the United States, including Turkey, Japan, Germany, the United Kingdom, Mexico and Australia, Muller said.
Avedro hopes to become the first company to make corneal collagen cross-linking available to U.S. patients. Its Phase III FDA trial, in which keratoconus and ectasia patients were treated, reached the required one year of follow-up in May.
Refractive regression expected after Opti-K
At NTK Enterprises, Inc., of Plano, Texas, refractive regression after thermal keratoplasty is part of the company’s business plan for treating presbyopia. The company is banking on the hope that middle-aged presbyopes will find its Optimal Keratoplasty (Opti-K) device and procedure so simple and effective for improving their near and distance vision that they will return every two years, indefinitely, for another “vision rejuvenation.”
Opti-K is a noninvasive form of laser thermal keratoplasty (LTK) performed with a continuous-wave thulium fiber laser with a sapphire applanation window for corneal epithelium protection. Sixteen laser spots are placed within the stroma in two concentric circles 6.0 mm and 7.2 mm in diameter.
Unlike with conductive keratoplasty, Opti-K leaves the corneal epithelium intact. Discomfort is minimal, and patients have clear vision immediately afterward.
Presbyopia isn’t stable
The refractive effect regresses over about two years, but retreatments can be done at any time, said Michael Berry, PhD, director of research for NTK.
“Thermal keratoplasty has flopped time and again partly because of the permanence question. But presbyopia isn’t stable. It is progressive, and it changes as we age,” Berry said.
Furthermore, after 40 years of age, there also is a natural progressive hyperopic shift, he said. He estimates that a 40-year-old emmetrope would require seven Opti-K treatments by age 70 to have functional near and distance vision.
Topography of treated eyes shows alternating sectors of steeper and flatter sections extending from the center of the cornea all the way out to the periphery, Berry said. However, the histology suggests that the laser spots neither destroy tissue nor shrink the collagen.
Hydration may be the mechanism
“We think we’re changing the hydrational state of the cornea. You see a kind of compaction of the anterior stroma, with more vacuoles, which is probably free water that has been squeezed out of the stroma,” he said.
In this model, stromal rehydration over time would explain regression.
Initially, NTK investigated keratoplasty with the thulium laser as a noninvasive, unilateral treatment to deliver monovision treatment, with perhaps a small element of multifocality to give presbyopic patients better near vision, Berry said. They expected patients to lose a slight amount of distance acuity.
“We were pleasantly surprised. We found that patients were not losing distance vision in the eye that had been corrected for near,” Dr. Berry said.
Later, studies of bilateral treatment of emmetropic presbyopes and hyperopic presbyopes were conducted in the Bahamas by K. Jonathan Rodgers, FRCS(C), DABO. He summarized the results of these studies at this year’s ASCRS meeting.
Near and distance UCVA improved significantly (P < 0.01 for all follow-up times) in both emmetropes and hyperopes (397 eyes, 199 patients), he said. There were no serious adverse events and no cases of clinically significant induced astigmatism (? 2 D).
In one group of emmetropic presbyopes (n = 63), the subjects gained up to 4.2 ± 2.0 lines of uncorrected near visual acuity one day after a staged secondary treatment. The final geometric mean was 2.0 ± 1.9 lines at 26 months.
A US FDA trial of Opti-K to correct hyperopia of 1.0 to 2.5 D is underway, with completion of one-year follow-up data expected in November 2012.
LaserACE may restore accommodative biomechanism
The LaserACE procedure ablates 600-micron laser spots in the sclera with the aim of restoring the accommodative biomechanism. The excisions are presumed to decompress stiff scleral tissue of the ciliary muscle, freeing the muscle to contract normally.
The company behind LaserACE, Ace Vision Group, reported this spring that their laser procedure restored approximately 1.5 to 2.0 D of accommodation in a group of presbyopes in a multicenter international preliminary study.
More studies planned
The company plans to move quickly this year and next to launch follow-up corroborative studies at several international sites. The first is planned as an efficacy study conducted in Canada and is expected to begin in about three months. This is scheduled to be followed in early 2012 by concurrent international trials with similar protocols.
Rick Potvin, the company's chief scientific officer and director of clinical research, will manage the studies. Marguerite McDonald, MD, FACS, is Ace Vision's global medical director.
The goal of the studies is the objective measurement of accommodation and comparison with an age-matched control group. Additional studies will be conducted in Taiwan, where the company's VisioLite laser recently was approved by the Taiwan FDA, and in two to three European and South American countries that have not been chosen yet, said AnnMarie Hipsley, DPT, PhD, founder and president of Ace Vision.
She said that results from these studies will form the foundation for initial discussions with the FDA about the LaserACE procedure, which has not been approved for use in the United States.
At the 2011 ASCRS meeting in San Diego, Hipsley and colleagues reported results from their multicenter retrospective, observational analysis of 67 consecutive patients (134 eyes) ranging in age from 37 to 68 who underwent bilateral LaserACE .
“We see some pretty compelling findings,” Hipsley said in an interview. “We see an improvement in vision in all ranges, with acuity levels stable for 18 months.”
“There is 1.25 D to 1.5 D of accommodation restored by the surgery and this remains stable through the 18-month time period. Significantly, there was no loss of distance vision and no reported increase in visual disturbances. And we see no greater variance in the distance VA than 0.5 D from preoperative levels,” she added.
There was an associated 3.1 mm average decrease in IOP, also stable at 18 months, but it is unclear whether this was a true IOP drop or an effect due to the increased plasticity of the sclera. She said the company planned to investigate this further.
The visual acuity data reported at ASCRS included these figures:
- At near, 89 percent of patients had UCVA of J3 or better postoperatively compared with 0.04 percent J3 to J4 before surgery.
- At intermediate distance, 89 percent were J3 or better postoperatively compared with 19 percent J3 to J4 preoperatively.
- No statistically significant loss in distance visual acuity was demonstrated, while there was evidence of improved distance visual acuity in some patients.
Patients were assessed with the i-Trace aberrometer (Tracey Technologies) and a custom-designed COAS-HD (AMO-Wavefront Sciences) with Dynamic Stimulation Aberrometry (Optana-Zeiss).
The subjects showed 2.0 to 5.5 D of accommodation on these objective tests, Hipsley reported. A separate analysis of accommodation data from 111 LaserACE patients found the postoperative improvements statistically significant (P < 0.001).
“Most procedures that address presbyopia compromise a portion of the dynamic vision range, mostly distance vision,” Hipsley said. “The LaserACE is the only current presbyopic procedure to restore natural dynamic accommodation without implants and without altering the existing geometry and optics of the eye.”
Diamond matrix pattern ablation
To perform LaserACE, the surgeon uses the patented curved 600-micron sapphire tip of an erbium-YAG laser hand piece to ablate a diamond matrix pattern of nine laser spots into each oblique quadrant. At the end of the procedure, the micro-excisions are covered with a doughnut-shaped layer of collagen to preserve patency of the ablations.
The erbium-YAG laser used in the procedure, Ace Vision's VisioLite, already has the CE mark and FDA approval for treating soft tissue around the eyes, although this is without specific claims. It recently was approved by Taiwan FDA, with China FDA approval pending. However, Ace Vision is not making the laser available for sale while the presbyopia trials continue, Hipsley said.
Financial Interest Disclosures
Dr. Marguerite McDonald is the global medical director for Ace Vision.