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New Findings from Ophthalmology, AJO and Archives
American Journal of Ophthalmology:
Roundup of Other Journals:
Focus On Ophthalmology
Chung et al. have found a novel association between erectile dysfunction (ED) and open-angle glaucoma (OAG), with ED patients experiencing a 2.85-fold greater risk of a prior OAG diagnosis than those individuals without a diagnosis of ED. The authors note this study is the first to document the association between ED and OAG in a population-based data set, which suggests that a common mechanism may be present in the two conditions.
The authors used data from the Longitudinal Health Insurance Database 2000 in Taiwan to identify 4,605 patients with ED and 23,025 individuals as controls. They used conditional logistic regression analysis, adjusting for patients’ monthly income, geographic location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity and alcohol abuse. Among all patients, prior OAG was found in 137 (0.5 percent)— 53 individuals with ED (1.1 percent) and 84 without ED (0.4 percent).
The authors recommend conducting prospective studies to develop clinical guidelines for evaluating concurrent or subsequent ED in patients with OAG.
In a controlled trial, Jiang et al. found that the incidence of clinically significant IOP elevation after laser peripheral iridotomy (LPI) is low in angle-closure suspects. They also discovered that eyes in which a higher number of laser pulses were used and those with shallower central anterior chambers were at increased risk for IOP spikes after LPI. Specifically, LPI in primary angle-closure suspects resulted in an increase in IOP of 8 mmHg or greater in 9.8 percent of cases at one hour and 0.82 percent of cases at two weeks.
The study involved 734 Chinese patients, aged 50 to 70 years, with suspected primary angle closure. One eye underwent iridotomy using an Nd:YAG laser, and the untreated fellow eye served as the control. The authors measured IOP at one hour and at two weeks after treatment.
Employing thin-sectioned MRI technology, Kim and Hwang demonstrated that the abducens nerve is present on the affected side in patients with type 2 Duane’s retraction syndrome (DRS), the rarest type of DRS.
The authors conducted a retrospective review of ophthalmologic examination medical records. They then performed thin-sectioned MRI at the brainstem level on 12 patients who presented with the typical signs of type 2 DRS, including adduction deficit; globe retraction; narrowing of fissure on adduction; and upshoot, downshoot, or both.
In vivo confocal microscopy (IVCM) has yielded insight into the morphologic diversity of the transparent cornea in the aging eye. Hillenaar et al. identified four characteristic manifestations of normal corneal aging: stromal microdots, folds in the posterior stroma, opacification of the Descemet membrane and corneal guttae. The authors maintain that understanding the effects of aging on corneal morphology is essential in distinguishing between the signs of normal aging and degenerative disorders.
The observational, cross-sectional study involved 300 corneas of 75 healthy men and 75 healthy women, evenly distributed over five age categories: 20 to 29, 30 to 39, 40 to 49, 50 to 59 and 60 to 79. In addition to determining the four characteristic manifestations of corneal aging, the authors identified some features that were age independent, including bright superficial epithelial cells, dendriform cells and tortuous stromal nerves. The authors also found a novel corneal endothelium phenotype in four normal eyes of two participants, which they named “salt-and-pepper endothelium,” but they could not determine whether this was a morphologic variant of normal endothelium or a new condition.
American Journal of Ophthalmology
De Benito-Llopis et al. found that there is a reorganization of the stromal cell population soon after surface ablation with mitomycin C (MMC). They also identified a decrease in density of the stromal bed that compensated initially with an increase in the mid and posterior stroma. Corneal cellularity tended to normalize over time, and the mean cell density throughout the cornea seemed to maintain normal values, three years postoperatively.
The authors studied the effects of surface ablation with MMC on keratocyte population in a prospective, nonrandomized, interventional case series. They compared 32 eyes treated with surface ablation (with 0.02 percent MMC) with 32 nontreated eyes. Keratocyte density was measured three, 15, 36 and 42 months after the surgery in the anterior, mid and posterior stroma, and compared with control eyes.
At three months postoperatively, the authors found a lower stromal bed density than in controls, while the cell density was significantly higher in the mid and deep stroma. Three years after the surgery, the cellularity in the stromal bed had not significantly changed from the three-month follow-up. However, the density in the mid and posterior stroma had decreased to show no difference from controls. The mean cell density between the anterior, mid and posterior stroma was not significantly different from that of controls at 15 months as well as three years after surgery.
Kymionis et al. found that corneal collagen crosslinking (CXL) in thin corneas with a minimum thickness of less than 400 µm after epithelial removal resulted in a significant decrease in endothelial cell density. This finding was not related to other intraoperative or postoperative complications.
Twelve patients (14 eyes) were included in the study. All patients underwent riboflavin- and ultraviolet A–induced CXL using the standard CXL (Dresden) protocol. The authors evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction and topography at baseline and at one, three, six and 12 months’ follow-up. Images of the endothelium were acquired with a modified confocal scanning laser ophthalmoscope.
No intraoperative or postoperative complications were observed in the patient series. Mean minimum preoperative corneal thickness at the apex of the cone after epithelial removal and before riboflavin instillation was 373.92 µm. UDVA and CDVA improved from 0.25 and 0.40 to 0.27 and 0.49, respectively, at the last follow-up examination. There was a reduction of the mean keratometry readings from 51.99 D to 49.33 D at the last follow-up. A significant decrease of endothelial cell density was also observed (preoperative, 2,733; last follow-up visit: 2,441).
Stein et al. found that patients with untreated sleep apnea are at an increased risk for idiopathic intracranial hypertension (IIH) and nonarteritic ischemic optic neuropathy (NAION) compared with patients who received treatment.
They performed a retrospective, longitudinal cohort study to determine whether an association exists between sleep apnea and open-angle glaucoma, normal-tension glaucoma, NAION, papilledema or IIH, and whether treatment with continuous positive airway pressure affects the development of these conditions. They reviewed billing records for beneficiaries 40 years of age and older enrolled in a large U.S. managed care network from 2001 through 2007.
Incidences were determined for the above-mentioned conditions among the beneficiaries and were stratified by sleep apnea status. Cox regression analyses determined the hazard of each of these conditions developing among individuals with and without sleep apnea, with adjustment for sociodemographic, ocular and medical conditions.
Among the 2,259,061 individuals in the study, 156,336 (6.9 percent) had one or more sleep apnea diagnoses. The hazard of open-angle glaucoma was no different between persons with sleep apnea (either untreated or treated with continuous positive airway pressure) and individuals without sleep apnea. Similar findings were observed when assessing the hazard of developing normal-tension glaucoma. A significantly increased hazard of developing NAION, papilledema and IIH was observed among individuals with sleep apnea who were not receiving continuous positive airway pressure therapy (as compared with individuals without sleep apnea).
Similar increased risk for papilledema—but not for NAION or IIH—could be demonstrated among patients treated with continuous positive airway pressure for sleep apnea.
Archives of Ophthalmology
Van der Meulen et al. found that both corrected distance visual acuity (CDVA) and straylight are severely impaired in Fuchs dystrophy and that both of these aspects of visual quality improved significantly after Descemet stripping endothelial keratoplasty (DSEK).
Data were collected in an observational case series at the Academic Medical Center in Amsterdam and in a prospective interventional case series at the Mayo Clinic in Rochester, Minn. Phakic and pseudophakic eyes of patients with Fuchs dystrophy were included (99 eyes from the Academic Medical Center and 48 eyes from the Mayo Clinic). CDVA, straylight and corneal thickness were measured in all eyes. The Mayo group underwent DSEK with simultaneous phacoemulsification if the eyes were phakic pre-operatively, and the eyes were examined at one, three, six and 12 months after the procedure.
Preoperatively, eyes with Fuchs dystrophy had decreased CDVA and increased straylight compared with normal eyes. Younger patients were affected more by increased straylight than by decreased CDVA. Postoperatively, CDVA and straylight improved significantly at all follow-up examinations. Postoperative improvement in straylight was more predictable than that of CDVA and was correlated with preoperative straylight. Eyes with preoperative straylight higher than 1.33 logarithm of the straylight parameter consistently improved after DSEK.
Nouri-Mahdavi et al. found that increasing the frequency of visual field testing from yearly to twice a year leads to earlier detection of glaucoma progression.
The authors enrolled 381 patients (486 eyes) from the Advanced Glaucoma Intervention Study. Starting at year 1, every other visual field examination was deleted to create a low-frequency data set.
The original group was kept as the high-frequency data set. The incidence of progression between the two data sets was then compared using mean deviation and pointwise linear regression analysis.
Based on mean deviation criteria, 204 eyes (44 percent) in the high-frequency data set and 160 eyes (34 percent) in the low-frequency data set progressed. According to pointwise linear regression, 185 eyes (40 percent) in the high-frequency data set and 167 eyes (36 percent) in the low-frequency data set progressed.
Dhar et al. found that clinical genetic evaluation can be incorporated into the management plan of all retinoblastoma patients using a team approach to ensure timely evaluations and appropriate counseling. Genetic evaluations provided improved risk prediction for patients and family members and also prevented overutilization of clinical screening tests, which have potential morbidity for relatives not carrying an RB1 mutation.
This study focused on 81 retinoblastoma patients seen in one children’s hospital over an eight-year period. The researchers were successful in completing the evaluation in 65 percent of patients (similar percentages in both unilateral and bilateral cases). Early in the study period, testing included DNA sequencing, which was supplemented in later years by DNA copy number analysis and methylation. These supplementary analyses resulted in a larger number of definitive genetic test results. Overall, genetic analysis demonstrated the causative mutation in 90 percent of patients with bilateral retinoblastoma and documented the hereditary form of retinoblastoma in 17 percent with unilateral retinoblastoma.
The genetic results from the retinoblastoma patients were then used to accomplish definitive testing of 46 at-risk relatives (predominantly parents and siblings), which found that only six carried the mutation and required surveillance.
Roundup of Other Journals
Mataftsi et al. have found that a tapering regimen of fluorometholone (FML) for ocular surface disease in children constitutes a safe anti-inflammatory treatment option to avoid steroid-induced glaucoma.
The study was performed to address previous findings that showed a dose-dependent rise in IOP associated with FML. The authors note that these findings are key, given that ocular surface disease such as blepharo-kerato-conjunctivitis—which was the most common indication for FML in this study—can present significant ocular problems, especially in children under age 8. These patients may need prolonged treatment with FML to control the inflammation, and a tapering regimen may help them avoid steroid-induced glaucoma.
The retrospective case-note review involved 107 patients with a median age of 6 years. The maximum prescribed frequency for FML was four times daily, which was gradually reduced to once weekly in long-term cases. Post-FML IOP was formally noted in 51 of the 106 patient case notes and was less than 19 mmHg in all cases.
Previous research has shown that two common variants in the gene-encoding complement factor H (CFH) are responsible for 17 percent of cases involving age-related macular degeneration (AMD). In the letters section of Nature Genetics, Raychaudhuri et al. published their findings linking a rare penetrant mutation in CFH with a high risk of AMD. According to the authors, this discovery constitutes one of the first instances in which a common complex disease variant has led to the discovery of a rare penetrant mutation.
Other research has raised the possibility that rare CFH variants confer AMD risk, but investigators had not been able to identify a rare variant conferring risk of advanced AMD. On the assumption that rare functional variants might explain proof of involvement of CFH with AMD, the investigators used genotype data and high-throughput sequencing to discover the rare penetrant mutation. They interpreted results from this sequencing to suggest that loss-of-function alleles at CFH are likely to impact the risk of AMD.
According to the investigators, future studies that sequence the multiple complement-pathway genes associated with AMD in large numbers of patients may also reveal rare, highly penetrant alleles—which, in turn, could add to the understanding of the mechanisms of AMD.
O’Brart et al. have demonstrated that corneal collagen crosslinking induced by riboflavin and ultraviolet A appears to be an effective and safe treatment option not only to halt the progression of keratoconus but also to improve some visual and topographic parameters.
The authors developed an 18-month randomized, bilateral, observer-masked, prospective study, recruiting 24 patients with early to moderate bilateral keratoconus. One eye of each patient was randomly assigned to undergo the crosslinking procedure, and the other eye served as the control.
Orbscan II 3-mm and 5-mm keratometry, simulated astigmatism, cone apex power and wavefront measurements showed significant reduction in disease progression at 18 months in treated eyes. In addition, BCVA improved at 18 months. The only complication reported was transient recurrent corneal erosions in one treated eye.
FOCUS ON OPHTHALMOLOGY
Training the next generation of ophthalmologists comes at a cost. A new study has put a dollar amount on one small part of the cost equation. And though it wasn’t the study’s intent, the findings suggest that timing may be everything when devising the surgical simulation curricula that are mandated for all U.S. training programs.
In this study, Hosler et al. reviewed charts of all patients who underwent phacoemulsification cataract surgery over three years at Penn State Hershey Eye Center. They then measured how resident participation affected surgical time and nonsupply costs, including salary, wages and benefits for all operating room (OR) personnel.1
Residents took longer per case than attending surgeons—an extra 12 minutes and 41 seconds on average. The authors used the nonsupply OR cost of $8.30 per minute in calculating that each graduating resident added $8,293.23 to the annual cost.
Although the surgical learning curve is nothing new, this study quantified that the bulk of intraoperative learning occurs during the first six months of training. By the second half of the academic year, the difference between residents and attending surgeons was negligible.
Value to training. Commenting on the article, Preston Blomquist said, “This study says there is a cost of putting surgical residents in an OR. And it suggests that investment in simulators may be warranted, if their use is shown to decrease time in the OR.” While commending the study, Dr. Blomquist also expressed reservations about the ability of virtual simulators to mimic the stress of performing a first cataract surgery on a live human being. Dr. Blomquist is associate professor of ophthalmology at the University of Texas Southwestern Medical Center.
“The study did not aim to justify the cost of any particular surgical simulation program,” said Ingrid U. Scott, MD, MPH, study coauthor and professor of ophthalmology and public health sciences at Penn State University in Hershey, “but it does provide some data on what might be considered a reasonable investment in surgical simulator training.” Mastering the precise physical tasks of surgery in a simulated setting might better prepare residents for the OR, she said. Next, Dr. Scott plans to evaluate the impact of the Hershey Eye Center surgical skills curriculum, which includes a simulated surgical training component. She predicted that if an effect of the new surgical skills curriculum is demonstrated, it will be observed primarily in the first half of the academic year, or the first 25 to 50 percent of phacoemulsification surgeries performed by ophthalmology residents.
“Even though we do not want residents to speed through the surgery,” said Eduardo P. Mayorga, MD, chief of the ophthalmology service at Hospital Italiano, Buenos Aires, Argentina, “long surgery times may signal that the resident needs to spend more time in the wet lab.” He also recommended that the attending surgeon take over in cases where the resident has exceeded some predetermined time limit.
“I think this study confirms what we thought intuitively,” Dr. Blomquist said. “The only surprise is how quickly residents became competent in cataract surgery—as far as operative time.”
1 Hosler MR et al. Ophthalmology. 2012;119(1):95–98.
Drs. Blomquist, Mayorga and Scott report no financial interests.
Focus on Ophthalmology is an occasional series. It provides an in-depth look at an article selected by the editor-in-chief of Ophthalmology.