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No Femto Fix for PK Trauma
Femtosecond laser trephination of corneal transplants is thought to confer greater protection against wound dehiscence than traditional keratoplasty thanks to increased contact surface area between the graft and host, as well as the physics of the graft shape. But it may not be able to withstand some forms of trauma. A recent paper details the first reported case of traumatic globe rupture after a femtosecond laser–assisted penetrating keratoplasty (PK).1
“This reported case shows that a shaped keratoplasty wound created with the femtosecond laser is still subject to dehiscence from trauma,” the University of Texas Southwestern Medical Center surgeons wrote.
Wound dehiscence is a well-known complication of full-thickness corneal transplants, which had vertical edges on the graft and recipient bed until femtosecond lasers came along.
In the lab, laser-cut PK junctions (with colorful names like “top hat,” “mushroom,” and “zigzag”) have been shown to withstand substantially more intraocular pressure before dehiscing.2,3 Consequently, for several years, eye banks and cornea surgeons have been shaping PK tissue with femtosecond lasers to improve mechanical stability after transplantation.
But, as the case report demonstrates, laser-assisted PKs still carry some risk for wound dehiscence, said V. Vinod Mootha, MD, coauthor of the paper and associate professor of ophthalmology at UT Southwestern. “I don’t think you’re completely off the hook if you do a full-thickness PK procedure, even when you have a shaped edge to the graft and the recipient bed,” he said.
The study reports on a construction worker who suffered an initial eye injury in 2006 that lacerated his cornea and caused partial extrusion of the crystalline lens. Several months later, he underwent PK because of central corneal scarring and received a secondary IOL implant.
The femtosecond laser (IntraLase, AMO) gave the graft and bed “zigzag” edges, and the surgeons secured the graft in place with 12 interrupted sutures and a single, 12-bite running suture. Six months postop, they removed three superior and three inferior sutures to reduce astigmatism. BCVA improved to 20/25.
However, a year after suture removal (18 months post-PK), the patient was struck by rubber tubing from a compressor and sustained another traumatic eye injury. The trauma caused inferior corneal wound dehiscence with uveal prolapse and expulsion of the IOL. With the graft resutured, the man’s eye healed well—but his inferior iris was gone, he was aphakic, and his BCVA was 20/100.
Dr. Mootha said he could only speculate about the strength of the junction between the laser-trephined graft and the recipient bed in this patient. However, the transplant surgery occurred early in the evolution of laser trephination, and the zigzag shape the surgeons used was later shown to be one of the weaker profiles.3 (The top hat is one of the strongest.3,4)
Nor is it known how much pressure the accident applied to the globe. “There’s no way to measure the force of the injury. Not only did the wound dehisce but also an intraocular lens that was sewn in came out of the eye,” Dr. Mootha said.
The case details make it crystal clear, however, that there is another transplant problem the femtosecond laser cannot solve: persuading recipients to protect their transplanted corneas from trauma. On the day of his second catastrophic injury, the patient was working without wearing safety goggles.
1 Kruger MM, Mootha VV. Cornea. Published online April 3, 2012.
2 Bahar I et al. Cornea. 2008;27(2):209-211.
3 Gilmer W et al. Br J Ophthalmol. Published online June 13, 2012.
4 Maier P et al. Cornea. Published online March 8, 2012.
Dr. Mootha reports no related financial interests.
Back Pain Linked to Uveitis
When patients present with anterior uveitis, ask them about back pain. That’s the advice of Canadian researchers who measured the prevalence of inflammatory back pain in a group of patients with anterior uveitis.1
Anterior uveitis is often a presenting feature of inflammatory back pain—defined as back pain attributed to spondyloarthropathies, also known as HLA-B27–associated arthropathies. This group of diseases preferentially involves the axial skeleton. About 50 percent of patients with anterior uveitis are HLA-B27 positive, and the ophthalmologist may be their earliest medical encounter.
The retrospective study surveyed 141 patients diagnosed with anterior uveitis at a tertiary care specialist’s practice. All were asked the following four questions:
- Do you have morning back stiffness that lasts more than 30 minutes?
- Do you find improvement in back pain with exercise but not with rest?
- Do you wake up because of back pain during the second half of the night?
- Do you have alternating buttock pain?
Those who answered two or more questions positively were classified as having inflammatory back pain that warranted referral to a rheumatologist, said lead author Clara C. Chan, MD, clinical lecturer in ophthalmology and vision sciences at the University of Toronto.
Nearly half (46.8 percent) were classified with inflammatory back pain. The most common anterior uveitis etiologies and associations were the following: idiopathic; HLA-B27 positive without a diagnosis of spondyloarthropathy; and ankylosing spondylitis or infectious causes.
The questions were validated by a subgroup of 25 patients who underwent a complete rheumatologic assessment to verify their diagnosis. The classification criterion was 92 percent sensitive and 67 percent specific for the diagnosis of ankylosing spondylitis or an undifferentiated spondyloarthropathy.
Dr. Chan teaches residents to use the four-question screening tool. Since the study, she has introduced it in her practice. Patients with anterior uveitis should always be asked those four questions to ensure an early referral to the rheumatologist, she said. “It’s an excellent screening tool for inflammatory back pain.”
However, she warned against certain other tests for uveitis patients. “A number of ophthalmologists still order the rheumatoid factor and the antinuclear antibody blood tests, which are costly and unnecessary in the workup for adult patients with uveitis,” she said. Although children with juvenile idiopathic arthritis may develop uveitis, adult-onset rheumatoid arthritis is not a spondyloarthropathy and does not cause uveitis, she said. “It is important to clarify this misconception.”
The study also measured quality of life using the EuroQOL questionnaire. Patients rated the state of their health in five categories: mobility, ability with self-care, ability to perform usual activities, amount of pain or discomfort, and presence of anxiety or depression. Patients with inflammatory back pain had a significantly worse quality of life than those without back pain.
What’s the bottom line? “Our study supports the strong association between the spondyloarthropathies and anterior uveitis,” Dr. Chan said. “All patients with anterior uveitis should be considered to have inflammatory back pain unless proven otherwise.”
1 Chan CC et al. Am J Ophthalmol. 2012;153(60):1025-1030.
Herpesvirus Associated With Wet AMD
The precise events that contribute to neovascular AMD, the leading cause of vision loss in the elderly, are still uncertain, but recent studies implicate immune and inflammatory mechanisms as part of the process.
A team of researchers, including Richard D. Dix, PhD, professor of biology at Georgia State University and adjunct professor of ophthalmology at Emory University, and Scott W. Cousins, MD, professor of ophthalmology and immunology at Duke University, had already shown that wet AMD patients have high levels of antibodies to human cytomegalovirus (HCMV)—a common herpesvirus that infects up to 80 percent of adults worldwide. The group postulated that HCMV infection might also be a risk factor for wet AMD.
In a mouse model of AMD, the researchers found that the most severe choroidal neovascularization (CNV) did indeed develop in mice with chronic HCMV infection. In mouse macrophages in culture, the virus also caused production of high levels of vascular endothelial growth factor (VEGF).
Earlier, the cofactors for development of AMD were considered to be genetics, a high-fat diet, nicotine, and age. Now, according to Dr. Dix, “We have discovered that an infectious agent—a virus—is another cofactor. There is a new era opening where many chronic diseases may have an infectious agent origin or cofactor role.
“Our instincts told us we were correct. Not only was this validated in a mouse model, but we could also show that the virus was directly needed for production of the growth factor, since we could reverse that with an antiviral drug.”
1 Cousins SW et al. PLoS Pathog. 8(4):e1002671. doi:10.1371/jour nal.ppat.1002671.
At the Bench
Bacteria Mow a Path Into the Eye
Mucous membranes, including the one covering the conjunctiva, have a common defense against microbial pathogens: a phalanx of long membrane-associated mucin molecules, arrayed across the surface. These proteins are vertically aligned and packed together tightly, with one end attached to the apical end of epithelial cells.
“Think of the ocular surface as a field of grass. Each of these little membrane mucins is sticking out like a blade of grass. These blades are packed tightly together to prevent pathogens from getting inside the eye,” said Ilene K. Gipson, PhD, a senior scientist at Schepens Eye Research Institute and professor of ophthalmology at Harvard Medical School.
Isolated infections after ocular trauma or surgery are made possible by gaps in the mucin field. But it turns out that some bacteria don’t need external help to cause infections because they are able to mow the mucin molecules out of the way, Dr. Gipson’s research group discovered recently.1 Dr. Gipson has been researching the roles of mucins in the eye since the 1990s.2
In a series of experiments on cultured eye surface epithelium, the scientists found that the causative agent of bacterial epidemic conjunctivitis, Streptococcus pneumoniae (strain SP168), did indeed mow mucins off of ocular epithelial cells by releasing the enzyme ZmpC, a metalloproteinase. This is the first demonstration that bacteria can remove the protective mucin layer, and it will be important to see if other epidemic-causing pathogens use the same mechanism, Dr. Gipson said.
1 Govindarajan B et al. PLoS ONE. 2012;7(3):e32418. doi:10.1371/journal.pone.0032418.
2 Gipson IK. Invest Ophthalmol Vis Sci. 2007;48(10):4391-4398.