American Academy of Ophthalmology Web Site: www.aao.org
News in Review
A Look at Today's Ideas and Trends
As the Joint Meeting of the Academy and the Middle East Africa Council of Ophthalmology approaches, EyeNet brings you a preview of some of the papers to be presented there. Chairs in charge of several paper sessions each selected one abstract that constitutes important news in the field or is illustrative of a trend. Although only five subspecialties are represented below, there also will be paper sessions for intraocular inflammation/ uveitis, neuro-ophthalmology, oculoplastics and pediatric ophthalmology. Look for a complete list of papers in the Final Program or Pocket Guide or at www.aao.org/programsearch10.
No Benefit to Larger Graft
In a classic example of bigger not always being better, larger corneal grafts do not outperform their smaller counterparts when it comes to protecting against endothelial cell loss in Descemet-stripping automated endothelial keratoplasty (DSAEK).
This finding emerged in a nonrandomized comparative trial conducted by Mark A. Terry, MD, and his coauthors to compare outcomes of different graft sizes in eyes with Fuchs dystrophy.
The results indicate that different graft sizes did not produce statistically significant differences in postoperative cell counts, cell survival or graft survival, even three years out from surgery.
Of the 331 eyes in the study, 159 had received grafts of 8.0 mm or smaller, while the remaining 172 had received grafts of 8.5 mm or larger.
At the six-month postop mark, mean cell loss was 23 percent for the smaller grafts vs. 24 percent for the larger grafts, but the difference was not statistically significant, said Dr. Terry, lead author of the study and director of cornea services at Devers Eye Institute in Portland, Ore. At one year, the rate of cell loss was the same in both groups (24 percent). Two- and three-year rates for smaller and larger grafts, respectively, were 26 percent vs. 25 percent and 34 percent vs. 37 percent, respectively. “Again, the differences were not statistically significant,” Dr. Terry noted.
He added that most graft studies have tracked six-month endothelial outcomes, with only a handful following patients for as long as two years. Despite the lack of data, the perception is that larger-diameter grafts confer greater protection. “Many surgeons are putting in larger corneal grafts with the thought that they will provide better postoperative endothelial cell counts,” said Dr. Terry, “but it just isn’t true. Bigger is not always better—at least for endothelial transplants!”
Dr. Terry reports no financial interests in this study.
Biologic Fibrin Sealant vs. Nylon Sutures
Ophthalmologists in Spain have conducted a prospective nonrandomized study of 57 glaucoma patients to evaluate the safety and effectiveness of a biologic fibrin sealant (Tissucol Duo) used in closing the conjunctival flap in trabeculectomy, compared with use of continuous 10/0 nylon suture. Other ocular surgeries, such as pterygium surgery, have demonstrated good surgical outcomes using fibrin sealant for conjunctival closure.
In this study, 28 patients were assigned to the fibrin sealant group and 29 patients were assigned to the suture group. The researchers found no significant difference in intraocular pressure between the two groups, but ocular discomfort was significantly lower in the fibrin sealant group for two weeks after the surgery. “Biologic fibrin sealant is a secure and effective alternative for conjunctival closure in trabeculectomy,” said Jose María Martínez de la Casa, MD, PhD, who is a glaucoma consultant at the Hospital Clínico San Carlos, Madrid and a coauthor of the study. “It also shortens the duration of surgery.”
Two of the 28 patients in the fibrin sealant group developed conjunctival dehiscence that required surgical correction with nylon 10/0 sutures at the 24-hour postoperative visit. Other complications, such as mild hyphema and shallow anterior chamber, were similar in both groups. One patient in the suture group had a mild suprachoroidal hemorrhage, which resolved without surgical intervention.
“In the long term, the biological sealant could result in less fibrosis than is induced by the nylon sutures,” said Omar Rayward, MD, lead author of the study and resident at the Hospital Clínico San Carlos.
Another issue affecting the use of fibrin sealant: It is more expensive than nylon sutures. This drawback could be remedied if fibrin sealant were manufactured in smaller amounts, said Dr. Rayward. Currently, fibrin sealant comes in a pair of 2-ml vials (one for the blood plasma protein fibrinogen and one for the coagulating enzyme thrombin) at a cost of approximately $250. This volume far exceeds what is needed for conjunctival closure in trabeculectomy. A pair of 0.5-ml vials would be sufficient and would cost about $63, Dr. Rayward estimated.
Drs. Martínez de la Casa and Rayward report no financial interests.
Fenretinide Fights Dry AMD
Fenretinide has shown promise in reducing the growth of lesions associated with geographic atrophy.
Trial data involving 246 subjects with the most advanced stage of dry AMD showed that both 100-mg and 300-mg doses of fenretinide reduced the rate of lesion growth compared with placebo. The phase 2b clinical trial, initially sponsored by Sirion and later by ReVision Therapeutics, is one of the first large clinical trials to use a pharmacological approach to treat dry AMD, said Jason S. Slakter, MD, lead author of the study and clinical professor of ophthalmology at New York University.
Dr. Slakter, who is performing the imaging evaluations for the trial, said lesion size was measured using fundus autofluorescence, fundus photography and fluorescein angiography. Patients also were monitored for incidence of CNV, visual acuity, contrast sensitivity and reading rates.
The investigators observed that fenretinide reduced the number of patients who converted from dry to wet AMD by nearly 50 percent, highlighting some of fenretinide’s potential anti-inflammatory and antiangiogenic effects.
“The possibility of a drug reducing the incidence of CNV in dry AMD is very exciting, as there is currently no treatment for the prevention of wet AMD,” Dr. Slakter said.
Fenretinide is an oral vitamin A–binding antagonist designed to interrupt the normal visual cycle and thus reduce the toxic waste buildup that is part of that cycle. Accumulation of the toxins, known as lipofuscin, has been implicated in the pathogenesis of AMD.
The only negative effect that the investigators found in the preliminary analysis was a slight reduction in night visual function. However, this was anticipated since fenretinide also affects the rods, which are responsible for night vision, Dr. Slakter explained. In fact, the complaints of night blindness “were almost reassuring because that tells us the drug is having the desired physiologic effect on the cells in the back of the eye.” He added that the effect was dose-related, with more complaints reported at the higher dose.
The next step, assuming the findings show an overall effect, is a phase 3 trial. In the meantime, Dr. Slakter mused on the prospect of having something to offer patients, other than “antioxidant vitamins, green vegetables and avoidance of smoking.”
Dr. Slakter receives grant research support through the Digital Angiography Reading Center and through Sirion Therapeutics.
Inlay for Presbyopes
A plethora of treatment approaches exists for presbyopia—from corneal laser surgery to conductive keratoplasty to intraocular lenses. Researchers are now testing a newer option: the corneal inlay. Presbia’s Flexivue Micro-Lens is a minimally invasive and reversible technique for patients between the ages of 45 and 60.
With fixed powers available from 1.25 D to 3.25 D, this hydrophilic acrylic bifocal lens has a peripheral refractive zone that alters the refractive index of the cornea in the nondominant eye, said Ioannis G. Pallikaris, MD, PhD, lead author of the study and director of the Institute of Vision and Optics at the University of Crete, Greece.
Using wavefront analysis, Dr. Pallikaris and coinvestigators have found the inlay’s maximum effect occurs in the 3- to 3.5-mm central zone, decreasing when the optical zone enlarges.
“That means we have maximum effect mainly during near vision when the pupil becomes smaller,” said Dr. Pallikaris. “As a result, far vision is less influenced than with conventional monovision, an effect we call ‘smart monovision.’”
Investigating the safety and visual outcomes of the Flexivue Micro-Lens, Dr. Pallikaris and fellow researchers implanted the lens inside corneal stromal tunnels they created in the eyes of 15 patients, then followed them over a period of 12 months. “Femtosecond laser created consistent, customized and accurate corneal depth for the pocket,” said Dr. Pallikaris, who added that changing the direction of the pocket has the potential to eliminate astigmatism, too, particularly once software that’s in the works becomes available.
In this study, overall patient satisfaction rates were 98 percent, with patients reporting very good near and binocular vision—results good enough for patients to dispense with glasses in most cases, said Dr. Pallikaris. Glasses were needed under certain lighting conditions, however, and some patients experienced glare and halos, as well as decreased contrast sensitivity in the operated eye.
“Patient selection is critical to success,” said Dr. Pallikaris, explaining that clear eye dominance and tolerance for monovision are key. But the potential is great for upward of 400 million presbyopes worldwide, he said. He projects that patients in the United States can look for its launch in approximately four years.
Other corneal inlays implanted in the nondominant eye offer variations on this theme. The Kamra inlay (AcuFocus) uses an opaque circular micro-disc combined with a pinhole pattern to increase the depth of focus, and the PresbyLens (ReVision Optics) microscopically reshapes the cornea. By contrast, the Flexivue is a transparent lens with diopter power. Implanted in a corneal pocket instead of a flap, he said, it offers greater stability and less impact on the biomechanics of the cornea without influencing the transparency of the cornea.
Dr. Pallikaris reports that he is chair of the medical advisory board of Presbia.
Femtosecond, Crystalens: Early Results
With an interest in determining whether the femtosecond laser’s capsulotomies lead to improved refractive performance by the Crystalens HD (Bausch + Lomb), a refractive/cataract surgeon performed 50 implants of the accommodating IOL after 100-percent femtosecond laser cataract surgery.
Stephen G. Slade, MD, in private practice in Houston, used the femtosecond laser from LenSx for the corneal incisions and capsulotomies, and for cracking or softening the nucleus.
“So far, the results have been excellent,” Dr. Slade said in an interview prior to completion of the follow-up on which he will report in Chicago.
If a capsulorhexis is circular and of the correct size, the posterior capsule can wrap evenly around the IOL edge, distributing capsular forces on the lens equally. This is important when a presbyopia-correcting IOL gains add power by vaulting forward, as does the Crystalens (Bausch + Lomb). For this group of patients, the capsulorhexis was set at 5.5 mm (5.0 mm optic).
“Because we’re controlling the size of the capsulorhexis, and because it is perfectly circular, this appears to be standardizing the capsular contraction and the refractive stability,” Dr. Slade said. “The powers seem to be more standardized. This will be an advantage for every IOL.”
FDA clearance of the LenSx laser for nuclear fragmentation led Dr. Slade to begin using the femtosecond laser for cataract surgery nearly exclusively.
“Surgeons come up to me all the time and say, ‘I don’t need a femtosecond laser because I can do a perfect capsulotomy of any size I want with a bent needle or forceps.’ But we did another series where we compared laser capsulotomies vs. handmade traditional capsulotomies, and the results were striking,” he said.
“You think you’re doing a perfect capsulotomy with a bent needle—but measure it. You’ll discover that you’re not even close. You just can’t do it,” he said, then added: “You can’t, you can’t, you can’t!”
In porcine eyes, Nagy et al. found that 5-mm capsulorhexes averaged 5.88 ± 0.73 mm (manual) and 5.02 ± 0.04 mm (laser).1
1 Nagy, Z. et al. J Refract Surg 2009;25(12):1053–1060.
Dr. Slade is medical director for LenSx and a consultant for Bausch + Lomb.