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Questions About Pressure After CXL
In eyes with keratoconus, does IOP rise after corneal collagen cross-linking (CXL)? While a team of Greek researchers reported a significant increase in Goldmann applanation tonometry (GAT) measurements of IOP, they were not able to conclude whether the pressure rise is real.1
“We cannot be certain if the increase in measured IOP is an overestimation or an increase in ‘true’ IOP, or both,” said Michael A. Grentzelos, MD, coauthor of the study and a research fellow at the Institute of Vision and Optics at the University of Crete, in Greece.
CXL, which is still awaiting FDA approval, was first reported in 2003 as a novel approach to arresting the progression of keratoconus and LASIK-induced ectasia. It involves topical administration to the cornea of a solution of vitamin B2 (riboflavin), which is then activated by ultraviolet-A light for about 30 minutes. The technique stiffens the cornea by inducing the formation of strong chemical bonds between collagen fibrils. The result is a preservation of the cornea’s natural dome-shaped architecture, rather than the cornea growing steep and irregular.
The Greek study, a prospective case series of 55 eyes in 55 patients, was reported as possibly the first to directly evaluate the effect of CXL on IOP using Goldmann applanation tonometry (GAT). IOP was measured prior to CXL, then at six and 12 months after the procedure. Mean pre-CXL pressure was 9.95 mmHg. At six months, IOP rose to 11.40 mmHg; at 12 months, IOP was 11.35 mmHg. No intraoperative or postoperative complications occurred.
The researchers have continued to closely monitor the patients after the 12-month follow-up to determine how long the pressure rise lasts, Dr. Grentzelos said.
One theory as to why measured pressure rises following CXL is that corneal stiffening is correlated with an increase in corneal rigidity. Corneal rigidity, an expression of the elastic quality of the eye’s globe, may have a substantial and variable influence on IOP measurement. “We believe that this increase in corneal rigidity and the biomechanical alterations after CXL may induce the increase in the measured IOP of those patients,” Dr. Grentzelos said. He stressed that this hypothesis has not been proven.
Because the type of tonometer may affect the pressure reading, the researchers, led by George D. Kymionis, MD, PhD, are currently testing other measuring devices. They hope to discover whether other devices, including the dynamic contour tonometer, will corroborate the IOP measurements obtained by GAT.
The truest measure of IOP could be obtained using an in vivo manometric device. That’s the best method for verifying whether the pressure rise is real or an artifact of the biomechanical changes induced by CXL, Dr. Grentzelos said.
With so many unanswered questions, it’s too soon to make any clinical recommendations, Dr. Grentzelos said. For now, clinicians should be mindful of the preoperative IOP levels of post-CXL patients when making a diagnosis and proposing treatment. “If glaucoma is suspected in a [CXL] patient, the increased IOP may be partly or entirely attributed to the CXL treatment,” he said. “This is important information that clinicians should take into account before making a diagnosis.”
1 Kymionis, G. D. et al. J Cataract Refract Surg
Dr. Grentzelos and coauthors report no financial or proprietary interests related to this study.
DSEK Patients Over 50: Beware of Cataracts
People older than 50 appear to be much more likely than younger patients to develop a cataract after Descemet stripping endothelial keratoplasty (DSEK), an Indianapolis research team has reported in the British Journal of Ophthalmology.1
Their study showed that one year after surgery, 31 percent of the phakic patients past age 50 (n = 40) had developed cataracts and had undergone phacoemulsification surgery. By three years postop, the probability for this had risen to 55 percent. This compared with zero cataract extractions at one year postop in the phakic patients younger than age 50 (n = 20). At three years, the probability of cataract surgery in this group was 7 percent (p = 0.0005).
The researchers reviewed the results from 1,050 DSEK procedures performed by one surgeon during a five-year period. Sixty of the patients remained phakic after surgery. If a patient had bilateral DSEK, only the first eye was included. The mean age at the time of cataract extraction was 57 ± 7 years (range 45 to 69 years). Overall, 26 eyes formed cataracts postoperatively (43 percent); at the three-year mark, the cataract had been extracted from 22 (37 percent) of them.
Knowing about stratification of risk by age is important because patients with endothelial failure are having DSEK earlier in life than they did when penetrating keratoplasty was their only option, said study coauthor Francis W. Price Jr., MD, a cornea surgeon and president of Price Vision Group, Indianapolis. “The risk of losing an eye due to DSEK is a lot lower than it was with PK, both during surgery and postoperatively due to trauma,” he said. “With PK you advised people, ‘Maybe you want to wait for the surgery until you’re much older.’ But with DSEK they are having the procedure much, much sooner,” he said.
Yet, as DSEK developed over the last decade, surgeons have wondered whether the risk of postop cataract might justify concurrent cataract surgery in all DSEK patients, said the study’s lead author, Marianne O. Price, PhD, executive director of the Cornea Research Foundation of America.
This study suggests the answer is no, she said. “For younger people, not only are they less likely to develop a cataract quickly but they’re more likely to have accommodation if you leave their crystalline lens in,” she said. “So it’s important for the patient younger than 50 to know that their risk of cataract in the first three years after DSEK is low. Surgeons should have that discussion with patients to assure that they understand,” she said.
“In American population studies, the rate of cataracts is between 3 percent and 4 percent for people in the 43 to 64 years age group, whereas the rate was 42 percent in this age range in the DSEK cohort,” the researchers write in the BJO report, offering support from the literature.2,3,4
In addition, the researchers had reassuring news about the outcomes of the cataract surgeries subsequent to DSEK. All were uneventful, without intraoperative or postop complications, they said. This contrasts with penetrating keratoplasty, after which cataract surgery has been associated with greater risk of graft failure.5,6
1 Price, M. O. et al. Br J Ophthalmol
2 Klein, B. E. et al. Ophthalmology
3 Leibowitz H. M. et al. Surv Ophthalmol
4 Klein, B. E. and R. Klein. Arch Ophthalmol
5 Payant, J. A. et al. Cornea
6 Martin, T. P. et al. Ophthalmology
Drugs for AMD Not Associated With Death
In a retrospective cohort study of nearly 150,000 Medicare beneficiaries, researchers at Duke University have unearthed no evidence of concern about systemic complications of three drugs currently used to treat neovascular age-related macular degeneration.1
Using photodynamic therapy as an active control group, the study looked at associations between intravitreal therapies for AMD—ranibizumab (Lucentis), bevacizumab (Avastin) and pegaptanib sodium (Macugen)— and four major systemic adverse events: death, stroke, heart attack and bleeding.
“Our expectation was to find some risk association,” said coauthor Scott W. Cousins, MD, director of the Duke Center for Macular Diseases at the Duke University Eye Center in Durham, N.C., especially given the increased risk of arterial thromboembolic events in patients receiving systemic bevacizumab for colorectal cancer.
“All three of the drugs get out of the eye within hours at levels that can have physiological impact, including on the fellow eye,” said Dr. Cousins. “And, nature has a way of prolonging the circulation of the full-length antibody, which is why an antibody intravenously injected can stick around for up to a month.”
Yet, two years of data from 2005 through 2006 found no statistically significant increase in adverse events with any of the three drugs compared with photodynamic therapy. The study also showed the risk of mortality was significantly lower with Lucentis than with photodynamic therapy (hazard ratio, 0.85); the risk of myocardial infarction was also lower (0.73).
“However, it is impossible to believe that Lucentis is safer than photodynamic therapy,” said Dr. Cousins, pointing to several confounding variables to consider, including regional differences in utilization of drugs, number of injections received, or high-risk subsets of patients with previous recent heart attack or stroke.
Along with exploring factors like these in the next round of database analysis, the researchers hope to look at two more years of data in the near future.
Dr. Cousins is an investigator/collaborator for clinical research, grantee and paid scientific adviser/ consultant for Genentech and Eyetech.
1 Curtis, L. H. et al. Arch Ophthalmol
Genetics of Fuchs Found
The genetic basis for Fuchs corneal dystrophy (FCD) has been discovered by researchers in Oregon and Minnesota.1 “We found that a genetic variation in the transcription factor 4 (TCF4) gene significantly contributes to the development of FCD. The primary value of our discovery is providing insight into the biology of the disease. For the first time, we have a clear path along which to design studies that could lead to prevention and/or treatment,” said lead investigator, Albert O. Edwards, MD, PhD, of the Institute of Molecular Biology at the University of Oregon in Eugene.
Approximately 5 percent of U.S. citizens, age 40 and older, are affected by FCD, which is clinically defined by guttae that develop under the corneal endothelium. Although prospective studies have not been performed, “we can say that 71 percent of our study patients with guttae had one or two copies of the risk variant, while 27 percent of age- and gender-matched controls without guttae had the risk variant. In fact, patients with the one copy of the risk variant were 5.5 times more likely to have guttae, and patients with two copies of the risk variant were 30 times more likely to have guttae,” Dr. Edwards said. Further, Dr. Edwards presented a poster at the Academy’s 2010 Joint Meeting showing that patients with vision loss from FCD were 275 times more likely to carry two copies of the risk variant than people without guttae.2
Because corneal edema associated with FCD may progress after cataract surgery, these findings may be of interest to ophthalmologists who perform refractive or cataract surgery. However, Dr. Edwards does not see value in large-scale genetic testing at this time: “We do not recommend genetic testing until a treatment other than surgery is available because a clinical examination by an eye doctor using specular biomicroscopy can diagnose Fuchs.”
1 Baratz, K. H. et al. N Engl J Med
2 Edwards, A. O. et al. Poster #355, Genetic variation increases the severity of Fuchs corneal dystrophy. Presented at the American Academy of Ophthalmology Joint Meeting, Monday, Oct. 18, 2010.
EyeNet thanks Christopher Rapuano, MD, and William B. Trattler, MD, for their help with this issue’s News in Review.