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Rewriting the Story of Fuchs Dystrophy
Has the pathophysiologic story of Fuchs endothelial corneal dystrophy (FECD) now been rewritten? Apparently so. A consortium of researchers has found a clear correlation between changes in central corneal thickness (CCT) and the severity of FECD, suggesting a progressive, rather than precipitous, course of the disease—even at early stages before clinical signs are evident.1
Using a cross-sectional study design and a sample of 1,610 eyes from a subset of index cases, family members, and unrelated control subjects, investigators with the NEI-funded FECD Genetics Multi-Center Study Group at 29 clinical sites around the country measured CCT changes using ultrasonic pachymetry. They then analyzed the correlation between CCT changes and disease severity, which was based on a 7-point scale of guttae confluence and development of corneal edema.
“We did not expect to see a progressive increase in thickness at the lower grades—with as few as 1 to 2 mm of confluent guttae,” said co-principal investigator Jonathan H. Lass, MD, professor and chairman of ophthalmology and visual sciences, Case Western Reserve University, and director, University Hospitals Eye Institute, in Cleveland.
That’s because the conventional wisdom has been that full-blown Fuchs with corneal thickening does not come into play until later stages, when the number of functioning endothelial cells is no longer adequate to prevent endothelial decompensation and corneal edema.2-4
In the past, it was thought that as the barrier function declined, compensatory mechanisms increased the pumping ability, which acted upon the remaining healthy endothelium until the disease reached a tipping point, said Dr. Lass. “We generally thought that the cornea maintained normal thickness until the disease was advanced, so the repeated measurement of increasing thickness at early stages had not been considered.”
Although ultrasonic pachymetry cannot distinguish changes in the thickness of individual corneal layers, said the investigators, the study nonetheless suggests that corneal hydration may be affected early on, possibly prompting subclinical thickening of the stroma.
Regular measurement of CCT changes provides an objective tool for disease monitoring, said Dr. Lass. Individuals with a family history (parent, brother, sister with Fuchs), particularly women, are at greater risk and warrant the closest monitoring of CCT.5
Measurement of CCT changes may also assist physicians in counseling their patients about surgical options for cataract surgery and Descemet stripping endothelial keratoplasty (DSEK), said Dr. Lass.
To date, he said, physicians have monitored patients by the extent of guttae, clinical development of corneal edema, and blurring of vision, particularly in the morning. And they have relied upon endothelial cell counts or absolute CCT measurements to determine when and how to pursue surgery.
A preoperative corneal thickness of 0.60 mm was once thought to be the threshold for consideration of an initial penetrating keratoplasty (PK) or PK combined with cataract surgery. However, a more recent study, in 2005, demonstrated that patients with corneal thickness as high as 0.64 mm, but without epithelial decompensation, had good success from cataract surgery alone; the researchers reported that less than 10 percent progressed to corneal decompensation requiring PK within an average follow-up of 1.6 years after surgery.6
The problem with using absolute numbers, however, is that there is great variability within the range of normal, as reported previously in studies such as the Ocular Hypertension Treatment Study7 and, more recently, in the FECD Genetics Multi-Center Study.5
“Regular monitoring of changes in corneal thickness may encourage the decision toward earlier intervention with cataract surgery, if the cataract is visually significant; DSEK alone, if the cataract is not visually significant; or DSEK in combination with cataract surgery before structural changes occur in the stroma, which may cause significant visual problems,” said Dr. Lass.
The FECD Genetics Multi-Center Study Group has formed a consortium with investigators at Duke and Johns Hopkins universities, continuing its primary work concerning the genetics of Fuchs dystrophy.
1 Kopplin LJ. Arch Ophthalmol. 2012;130(4):433-439.
2 Eghrari AO. Expert Rev Ophthalmol. 2010;5(2):147-159.
3 Wilson SE. Cornea. 1988;7(1):2-18.
4 Krachmer JH. Arch Ophthalmol. 1978;96(11):2036-2039.
5 Louttit MD. Cornea. 2012;31(1):26-35.
6 Seitzman GD. Ophthalmology. 2005;112(3):441-446.
7 Brandt JD. Ophthalmology. 2001;108(10):1779-1788.
Dr. Lass reports no financial interests.
A Comparison of Topical Anesthetics
Sometimes you get what you pay for. But when it comes to ocular anesthesia for intravitreal injection, inexpensive proparacaine drops produce equally high levels of patient satisfaction as more expensive lidocaine gel anesthetic.1
This finding is based on the responses of 120 patients who were randomized to three preinjection treatment groups and then asked to rate both the pain of injection and the overall injection experience.
Prior to injection, an equal number of patients received either 0.5 percent proparacaine hydrochloride drops; 3.5 percent lidocaine hydrochloride ophthalmic gel (Akten); or proparacaine drops plus 4 percent lidocaine-soaked cotton-tipped swabs applied to the injection site for 20 seconds.
Approximately 10 seconds postinjection, patients rated their discomfort associated with the lid speculum, needle insertion, and the burning sensation from a 5 percent povidone-iodine solution applied to the injection site following placement of the speculum. Patients rated discomfort on a scale from 0 (no pain) to 10 (worst pain ever). They also graded overall satisfaction with the injection experience on a scale ranging from “Awful” to “Excellent.”
Prior to conducting the study, John S. Pollack, MD, had tried all three topical anesthetic methods but couldn’t detect any difference in patient satisfaction. The study was designed to put his clinical observations to the test. Dr. Pollack is a partner with Illinois Retina Associates and assistant professor of ophthalmology, Rush University Medical Center, Chicago.
The results: All three groups reported low levels of discomfort as well as high levels of satisfaction with the entire process. There were no statistically significant differences among groups in any category.
There was, however, a difference in cost, which ranged from 3 cents for the proparacaine drops to 15 cents for the lidocaine gel. The proparacaine drops plus lidocaine-soaked swab cost 14 cents.
Going into the study, Dr. Pollack expected the combination anesthetic might provide the greatest pain control and the highest level of overall satisfaction. “But this was clearly an incorrect assumption,” he said.
The study has affected the way he practices. “Due to the high satisfaction rate and low cost associated with proparacaine drops, I now routinely use only proparacaine drops for ocular anesthesia prior to intravitreal injections.”
1 Davis MJ et al. Retina. 2012;32(4):701-705.
Dr. Pollack is a consultant to Alimera and AMO and owner of Clarus Acuity Group and Covalent Medical.
Trends in Practice
Laser vision correction is one of the most frequently performed procedures in ophthalmology, said refractive surgeon Ronald Krueger, MD, who has performed no small number himself—more than 20,000. But only about a quarter of comprehensive ophthalmologists recently surveyed by the Academy are performing either laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) procedures.
This is not a surprising result, given the cost or inaccessibility of the laser, the time that must be invested in training, and the level of comfort the surgeon must have with these refractive procedures, said Dr. Krueger, medical director of the department of refractive surgery at the Cleveland Clinic. These factors, combined with the fact that LASIK and PRK are elective procedures, help to explain why they’re still less commonly performed than cataract surgery, he said.
“I think comprehensive ophthalmologists who are well trained and very comfortable with the procedure can do a great job,” he said, adding that the personal investment in a cornea refractive fellowship to learn the nuances is advisable.
Still, Dr. Krueger is of two minds about generalists performing these procedures: On the one hand, he said, this could bring these procedures more into the mainstream, making them more acceptable and accessible to patients. “On the other hand, if ‘everybody’ is performing these surgeries, this is bound to increase the complication rate in the hands of those less experienced and scare some people away,” he said. “This is a concern because the primary reason why people are not having LASIK or PRK is fear.”
It is critical to maintain high standards for refractive surgeries, said Dr. Krueger. “If the general population sees that patients do extremely well in the hands of great surgeons, more people will undergo PRK and LASIK.” The refractive specialist who has the benefit of multiple procedures and extensive training under his or her belt will have more experience in identifying and avoiding poor surgical candidates, thus lowering complication rates, he said.
Dr. Krueger is a consultant for Alcon, Clarity, LensAR, and Presbia.
|CLINICAL INSIGHT. To better understand current practices on a number of topics, the Academy surveyed comprehensive ophthalmologists about how they would handle various clinical situations. This is the last in the series. To look back at past topics, visit News in Review going back to September 2011 at www.eyenetmagazine.org/archives.
Yellow Rings May Result From AMD Supplements
High-dose vitamin supplements for age-related macular degeneration (AMD) may add visible yellow rings to patients’ eyes, according to a group from the University of Pittsburgh.1
The case series of four patients found yellow, circumferential, peripheral corneal rings and subtle yellowing of the skin, especially on the palms. Serum carotene was markedly elevated in one patient and normal in two; the fourth patient was not tested. Two patients were enrolled in the AREDS 2 study; the others were taking eye supplements.
When he first noticed the rings, Andrew W. Eller, MD, said that he was concerned that patients were taking more than the recommended amount. “But as I looked into it, this was not the case, and I don’t think the rings have any clinical ramifications.” He added that if other physicians notice this phenomenon in their patients, they should “observe them, but don’t stop the vitamins.” Dr. Eller is lead author of the study and professor of ophthalmology at the university.
“I was surprised that, with as many patients as we’ve treated for AMD, no one else has identified this finding,” he said. “If we see it in some, why don’t we see it in more?”
The team concluded that the rings may be relatively common but not generally recognized because of their subtle appearance or misdiagnosis as arcus senilis. “The ring is more prominent along the superior limbus,” Dr. Eller noted.
When AREDS 2 finishes this summer, and the subjects are evaluated for the presence of the rings, he said that he will be interested to see whether “you can tell if patients are taking their vitamins by looking at their eyes.”
1 Eller AW et al. Ophthalmology. 2012;119(5):1011-1016.
Dr. Eller reports no related financial interests.