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New Findings from Ophthalmology, AJO and Archives
March's American Journal of Ophthalmology:
January's Archives of Ophthalmology:
Roundup of Other Journals:
Previous volume-outcome studies have shown that surgeons who perform more procedures obtain better patient outcomes than those who perform fewer procedures. Bell et al. hypothesized that this finding would hold true for cataract surgeons as well, and their results indicate that this is, indeed, the case.
The researchers examined health records of all cataract surgeries performed in Ontario, Canada, during a three-year period. In each year, the overall adverse event rate between one and 14 days after surgery was less than 0.5 percent. Surgeons performing 50 to 250 cataract surgeries per year had an adverse event rate of 0.8 percent; those performing 251 to 500 cataract surgeries per year had a rate of 0.4 percent; those performing 501 to 1,000 cataract surgeries per year had a rate of 0.2 percent; and those performing more than 1,000 cataract surgeries per year had an adverse event rate of 0.1 percent.
The authors suggest professional organizations consider developing recommendations about the appropriate number of cataract surgeries required for surgeons to maintain a high proficiency level.
Topical Interferon Alpha 2a for Mooren’s Ulcer
In the first patient, the topical interferon was administered as a single agent every two hours for the first week. After noticeable improvement, the treatment was tapered to one drop every four hours. After the first month, interferon alpha 2a was tapered to four times a day for the next two months. At this point, no further treatment was required, as there was no recurrence during the first year of follow-up. The second patient experienced a similar course.
The authors conclude that despite the limitations of the study, including the small number of cases, interferon alpha 2a may prove to be an effective treatment alternative in Mooren’s ulcer. They call for larger studies to confirm the safety of this treatment.
OCT-Measured Central Retinal Thickness and Visual Acuity in DME
While OCT measurements of retinal thickness represent an important tool in evaluating eyes with diabetic macular edema, members of the Diabetic Retinopathy Clinical Research Network have found that these measurements do not reliably correlate to visual acuity.
In this study, the authors measured retinal thickness with OCT and visual acuity with the Early Treatment Diabetic Retinopathy Study protocol in 210 patients (251 eyes) with DME. These individuals were enrolled in a randomized clinical trial of laser techniques. The authors documented a modest correlation between BCVA and OCT center-point thickness prior to focal laser photocoagulation, as well as a modest correlation between change in visual acuity and change in OCT center-point thickening through the first year following laser treatment. Despite this modest correlation, there was substantial variation in visual acuities at any given retinal thickness.
The authors conclude that OCT measurements do not reliably serve as a substitute for visual acuity information in the patients they studied.
Surgical Treatment to Stabilize and Improve Visual Function in Geographic Atrophy
Joussen et al. demonstrated the feasibility of surgical treatment to stabilize and improve visual function in geographic atrophy. Their method, performed on 12 patients, involved positioning an autologous, peripheral, full-thickness graft of retinal pigment epithelium, Bruch’s membrane and choroid under the macula.Translocation of the full-thickness graft generally resulted in a vascularized and functioning graft in these individuals. In addition, reading was possible for eight of the patients after six months. In seven patients followed for one year, visual acuity remained stable in five eyes and decreased in two eyes between six months and one year follow-up. However, the surgery was associated with a high risk for complications and visual loss; intraoperative complications occurred, and revisional surgery due to proliferative vitreoretinopathy was required in five eyes.
The authors call for longer follow-up to better understand long-term survival and functionality of the full-thickness graft. They speculate that refinement of the surgical procedures may reduce the complication rate for these patients.
Determining Source of Refractive Errors After Cataract Surgery
Jin et al. studied 22 eyes that underwent IOL exchange for correction of unexpected refractive errors after cataract surgery. Of the 22 eyes, five of the refractive errors had resulted from keratometry mistakes and three from incorrect axial length measurements. Three others were linked to the insertion of a wrong IOL.
While some of these mistakes could be avoided, other cases included in this study could not be linked to a specific cause. After the IOL exchange, 18 of the 22 eyes were within +0.5 D and 19 of 22 eyes were within +1 D of emmetropia. UCVA was 20/40 or better in 18 of 22 eyes, and BCVA was 20/40 or better in 21 of 22 eyes.
The authors suggest that errors in one eye should be considered a warning to modify the IOL calculation for the second eye in order to minimize postoperative refractive surprises.
American Journal of Ophthalmology
Cardiovascular Disease and Age-Related Macular Degeneration
The Women’s Health Initiative Sight Examination (WHISE) is an ancillary study of the Women’s Health Initiative’s clinical trial of hormone replacement therapy. Klein et al. analyzed data from the WHISE to examine the association of cardiovascular disease, CVD risk factors and CVD treatment with AMD.
This observational analysis of a randomized clinical trial included 4,288 women aged 63 years and older. Information on CVD and its risk factors was obtained from a standardized questionnaire and examination, and AMD was determined by standardized grading of fundus photographs.
The prevalence of AMD was 21.4 percent. Of those with AMD, 5.8 percent had signs of exudative AMD or pure geographic atrophy, limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were older age, smoking, systolic blood pressure, use of calcium channel blockers, history of diabetes and greater body mass index. History of myocardial infarction, stroke, use of statins or white cell counts were not associated with AMD.
Impact of Dry Eye Syndrome on Vision-Related Quality of Life
Miljanovic et al. evaluated the impact of dry eye syndrome (DES) on vision-associated quality of life.
In this cross-sectional study, 450 participants in the Women’s Health Study (WHS) and 240 participants in the Physicians’ Health Study (PHS) were sent a supplementary questionnaire asking how much their everyday activities were limited by symptoms of dry eye and to what degree problems with their eyes limited them in reading, driving, working at the computer, doing their professional activities and watching television. By design, one-third of study subjects had clinically diagnosed DES or severe symptoms and two-thirds did not. The authors used logistic regression to examine relationships of DES with reported problems in everyday activities within each cohort, and they pooled estimates using meta-analysis methods.
Of the participants invited, 85 percent completed the supplementary questionnaire, including 135 WHS and 55 PHS participants with DES, and 250 WHS and 149 PHS participants without DES. Controlling for age, diabetes, hypertension and other factors, those with DES were more likely to report problems with reading, carrying out professional work, using a computer, television watching, driving during the day and driving at night.
DES seems to be associated with a measurable adverse impact on several common and important tasks of daily living, further implicating this condition as an important public health problem.
Patching vs. No Patching After Bilateral Cataract Surgery
Stifter and Menapace compared two methods of postoperative dressing regimen: patching vs. “instant vision” without patching in a randomized, clinical trial.Sixty consecutive hospitalized, patients scheduled for cataract surgery under topical anesthesia on both eyes on different days were enrolled prospectively. In randomized order, one eye was patched for the first 24 hours postoperatively. The other eye was left open without patch to obtain instant vision. Both eyes received the same anti-inflammatory and antibiotic drop therapy.
Twenty-four hours postsurgery, no significant differences between patching and instant vision could be found for corrected and uncorrected visual acuity, corneal epithelial defects, conjunctival inflammation, anterior chamber flare and IOP. During the first 24 hours postoperatively, all tear film parameters were significantly worse in the instant vision eyes, indicating transient tear film instability. During the first four hours after surgery, pain scores in the instant vision eyes were significantly higher than in the patched eyes. At eight hours and beyond, there were no significant differences in any pain scores.
After experiencing both methods, 27 percent of the patients subjectively rated the two methods as equivalent; 8 percent of the patients preferred instant vision. Despite the benefits of instant vision’s immediately improved orientation, 65 percent of the tested patients preferred patching because of less pain and foreign body sensations, and psychological arguments.
The clinical examinations showed that both methods were equally safe for postoperative therapy. However, further efforts have to be made to increase the patients’ comfort with instant vision in the first hours after cataract surgery.
Subclinical Keratoconus Detected by Corneal First-Surface Higher-Order Aberrations
Buhren et al. investigated corneal higher-order wavefront aberrations of clinically inconspicuous fellow eyes in patients with early keratoconus in a prospective, comparative case series.
Twenty-three eyes (group 1) were newly diagnosed with keratoconus; 10 eyes (group 2) were asymptomatic fellow eyes that showed neither major topographic anomaly nor clinical signs of keratoconus; and 127 healthy eyes of 74 patients served as negative controls (group 3). A seventh-order Zernike decomposition of first surface aberrations was performed. The following measures were assessed for their usefulness to discriminate between clinically normal fellow eyes, keratoconus eyes and controls by plotting receiver-operating characteristic curves: single Zernike coefficients, higher-order aberration root mean square (HOA RMS) values, the Z3 index and the output values of discriminant analysis D13 (groups 1 and 3 data) and D23 (groups 2 and 3 data).
There were significant differences between group 1 and group 3 for 11 Zernike coefficients, Z3, total HOA RMS, coma RMS and third-order RMS. Group 2 and 3 showed significant differences only for the coefficients Z3-1 and Z5-1. The researchers also found that Z3-1, D13 and D23 discriminated between groups 1 and 3 with maximum sensitivity and specificity. For discrimination between groups 2 and 3, D23 turned out to be the best parameter, followed by Z3-1.
The authors conclude that clinically normal fellow eyes with early keratoconus showed significant differences of first-surface aberrations compared with normal eyes and could therefore be considered as eyes with subclinical keratoconus.
Archives of Ophthalmology
Klein et al. performed a study to identify the location of genes influencing the continuous range of refraction (the continuous spectrum of myopia to hyperopia).
The authors did linkage analysis on 486 families who participated in the Beaver Dam Eye Study. These analyses were conducted while controlling for the effects of age, education and nuclear sclerosis on refraction measurements.
The authors identified a novel region with strong evidence of linkage on chromosome 1q (multipoint P-value 0.0019). They also were able to replicate a region on chromosome 22q (multipoint P-value 0.0033) that had previously been linked to myopia in an Ashkenazi Jewish population. In addition to these two regions, a third region on 7p (multipoint P-value 0.0023) also provided modest evidence of linkage.
Previous work by these authors demonstrated that refraction is a complex trait influenced by multiple genes and environmental factors. Their confirmation of linkage to chromosome 22q in the current study provides very strong evidence that a gene influencing refraction is located on this region. Given the multifactoral basis of refraction, the finding that additional refraction genes may reside on chromosomes 1q and 7q is not surprising.
Future studies to identify the genes responsible for these linkage regions are under way. Their identification will help in determining the development of normal visual systems and how disruptions to this process lead to impaired vision. Furthermore, modification of the actions of such a gene may lead to a reduction in the risk of refractive error.
Identification of Novel Genetic Loci for IOP
Duggal et al. performed a genomewide linkage analysis of IOP in the population-based Beaver Dam Eye Study. Elevated IOP is a principal risk factor for primary open-angle glaucoma and this trait may strongly influence disease development.
Included in this quantitative-trait analysis were 1,978 individuals from 486 pedigrees. IOP was measured in each eye by trained observers using a Goldmann applanation tonometer. The higher IOP measurement in either eye was used in the analysis. In addition, treatment for elevated IOP, systolic blood pressure, age and sex were included as covariates.
Seven regions of interest were identified on chromosomes 2, 5, 6, 7, 12, 15 and 19. Of these, two regions, 2 and 19, had previously been identified as potential linkage regions for blood pressure. Each of these regions may harbor a gene that controls the magnitude and variation of IOP.
These findings may aid in the design of new treatments for ocular hypertension and subsequently control progression to glaucoma. In addition, they may aid in early identification of individuals at risk for primary open-angle glaucoma related to ocular hypertension.
Major AMD Susceptibility Alleles and Interactions With Modifiable Risk Factors
Schaumberg et al. found genetic predisposition and exposure to modifiable risk factors such as obesity and smoking can multiply the risk for age-related macular degeneration in adults.
Past research found that common variants in genes for complement factor H (CFH) and LOC387715 increase a person’s risk for developing AMD. This prospective study of 457 subjects who developed AMD and 1,071 age- and sex-matched controls further delineated the magnitude of susceptibility to AMD due to common variants in these two genes. Moreover, the authors asked whether these variants interacted with modifiable risk factors.
Participants with one and two copies of the Y402H variant of CFH were 1.98 and 3.92 times more likely to develop AMD, whereas those with one and two copies of LOC387715 A69S were 2.38 and 5.66 times more likely to have AMD, respectively. The fraction of AMD cases attributable to these two variants was 63 percent. Subjects who had two copies of each variant allele had a 50-fold increased risk of AMD. In addition, people with two copies of CFH Y402H were nine times more likely to develop AMD if they smoked and 12 times more likely to develop the disease if they were obese compared with individuals not possessing the genetic variant or reporting modifiable risk factors. Carriers of two variant alleles of LOC387715 A69S who smoked were 22 times more likely to develop AMD.
Researchers stress the importance of leading a healthful lifestyle for individuals who are genetically predisposed to AMD.
Ophthalmology summaries are written by Lori Baker Schena and edited by John Kerrison, MD. American Journal of Ophthalmology summaries are edited by Thomas J.Liesegang, MD. Archives of Ophthalmology summaries are written by the lead authors.
Previous research has shown that inherited variation in the complement factor H gene constitutes a major risk factor for drusen in dry age-related macular degeneration. DeWan et al. contend that a single-nucleotide polymorphism in the promoter region of HTRA1 (a serine protease gene on chromosome 10q26) is a significant risk factor for wet AMD.
They made this discovery by applying a whole-genome association mapping strategy to an Asian cohort. Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.
The authors propose a general model for the pathogenesis of AMD based on its two main characteristics, geographic atrophy with large drusen and neovascularization. Complement factor H influences the drusen that characterizes dry AMD, and HTRA1 influences choroidal neovascularization in wet AMD. These two processes can be combined, leading to composite phenotypes seen in some cases of AMD.
Yang et al. have found that a variant of the HTRA1 gene increases susceptibility to age-related macular degeneration.
The authors genotyped 581 AMD cases and 309 normal controls. They found that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1, is the most likely causal variant for AMD at 10q26. They estimate it confers a population-attributable risk of 49.3 percent.
The researchers found that the HTRA1 gene actually encoded a secreted serine protease. In addition, the risk allele was associated with elevated expression levels of HTRA1 mRNA and protein, a finding gleaned from preliminary analysis of lymphocytes and retinal pigment epithelium from four AMD patients. They also found that drusen in the patients’ eyes were strongly immunolabeled with HTRA1 antibody.
The authors conclude that these findings support a key role of HTRA1 in AMD susceptibility.
Patients with both cataract and glaucoma may benefit from 5-fluorouracil (5FU) phacotrabeculectomy, a combined procedure designed to remove the cataract while lowering IOP. Chang et al. conducted a retrospective, nonrandomized study of 45 5FU phacotrabeculectomies (PT group) and 47 5FU trabeculectomies (T group), looking at pre- and postoperative IOP, number of medications, visual acuity and complications.
In terms of reducing IOP, the T group experienced a significantly greater treatment effect. The T group had a 44.6 percent reduction in IOP and the PT group had a 31.2 percent reduction. In addition, the PT group required significantly more postoperative 5FU injections.
The authors note that these findings should be viewed in light of the advantages of undergoing one combined surgery, thus avoiding the potential complications associated with subsequent cataract surgery, including bleb failure. They note that patients with both glaucoma and cataract should consider 5FU phacotrabeculectomy surgery given that it does achieve effective IOP reduction. However, patients should be reminded that the magnitude of IOP lowering may be less than in 5FU trabeculectomies, and the number of interventions needed in the postoperative period might be more.
Posterior-assisted levitation (PAL) is a technique originally created to support a sinking nucleus. Later it incorporated an ophthalmic viscosurgical device to retrieve nuclear remnants and IOLs. In an effort to determine whether PAL is associated with a higher rate of complications, Por et al. performed a retrospective study of the outcomes and complications of 14 patients who had undergone PAL for dropped nucleus or nuclear fragments or for intraoperative or late subluxated posterior chamber IOLs.
The complications included one case of retinal detachment 20 months after PAL and one case of cystoid macular edema in a patient with previous anterior uveitis. BCVA was 20/40 or better in 11 patients. In the remaining three, one had retinal detachment, one had corneal edema/scarring and one had an unspecified problem.
The researchers conclude that PAL represents a relatively simple, noninvasive way to manage subluxated IOLs and retrieve nuclear fragments.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.