American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
September’s American Journal of Ophthalmology:
August’s American Journal of Ophthalmology:
August’s Archives of Ophthalmology:
July’s Archives of Ophthalmology:
Roundup of Other Journals:
According to Yonekawa et al., older age, unemployment, diabetes and a history of ocular disease constitute risk factors for incident visual impairment and monocular blindness in Latinos.
In this population-based cohort study, investigators performed a detailed history and comprehensive ophthalmologic examination of 4,658 Latinos aged 40 and older at baseline and four years later. The authors defined incident visual impairment as BCVA of worse than 20/40 and better than 20/200 in the better-seeing eye at the four-year follow-up exam if that eye had a previous BCVA of 20/40 or better at baseline. Independent risk factors for impairment included older age, unemployment and diabetes mellitus. The authors defined monocular blindness as BCVA of 20/200 or worse in one eye at four-year follow-up after BCVA of both eyes was better than 20/200 at baseline. Independent risk factors for monocular blindness included being retired or widowed, or having diabetes mellitus or any ocular disease at baseline.
These findings highlight the need for focused intervention strategies to prevent and treat modifiable risk factors among the fastest-growing segment of the U.S. population.
In calculating the individual risk for developing primary open-angle glaucoma (POAG) in patients with ocular hypertension, Brandt et al. have found that it is simpler, and just as accurate, to use IOP and central corneal thickness (CCT) as measured than it is to apply an adjustment formula to correct IOP for CCT. These results indicate that the influence of corneal thickness as a prognostic factor for POAG development is not entirely due to its effect on IOP measurement. Rather, CCT is a biomarker for structural or physical factors involved in the pathogenesis of POAG.
The study reanalyzed the prediction model from the Ocular Hypertension Treatment Study (OHTS) for the risk of developing POAG. The authors used the same five baseline variables as the OHTS (age, IOP, CCT, vertical cup-todisc ratio and pattern standard deviation), except that IOP was adjusted for CCT using different correction formulas. They found that C-statistics for prediction models using IOP adjusted for CCT by different formulas range from 0.75 to 0.77. This figure is no better than the original prediction model of 0.77, which did not adjust IOP for CCT.
The authors recommend downloading the free risk calculator found at ohts.wustl.edu/risk for a simple way to calculate the five-year risk of developing POAG for an individual with ocular hypertension.
Campochiaro et al. found that monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab for six months offered significant benefit in patients with central retinal vein occlusion (CRVO), resulting in mean improvements of 12.7 and 14.9 letters, respectively, from baseline BCVA letter scores. During the following six months, the benefit was maintained when injections were given as needed, resulting in a mean improvement in BCVA letter score of 13.9 in each of the treatment groups.
The prospective, randomized, double-masked clinical trial included 392 patients with macular edema after CRVO. Eligible patients were randomized 1:1:1 to receive six monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections. After six months, all patients with BCVA of 20/40 or worse or central subfield thickness of 250 µm or more could receive ranibizumab. No new ocular or nonocular safety events were reported.
These findings demonstrate that after a period of monthly treatment with ranibizumab, visual benefits can be maintained through close follow-up and re-treatment as needed. What this study does not address is whether even better visual outcomes could have been achieved if a monthly regimen had been continued through the second six months of the study.
According to Liu et al., one-eye therapeutic trials for IOP-lowering medications are based on two core assumptions: 1) There is a timedependent symmetrical IOP variation in the paired eyes, and 2) the extent of IOP reductions resulting from the drug treatment is equal in the paired eyes. In this database study, the authors tested these assumptions. They found a weak association between the right- and left-eye response to IOPlowering monotherapy or adjunctive therapy during a 24-hour period when single-pair IOP data were considered.
The authors retrospectively analyzed 24-hour data from the paired eyes of 66 patients undergoing bilateral monotherapy with latanoprost, travoprost, timolol or brimonidine and from 52 patients undergoing bilateral adjunctive therapy with brinzolamide or timolol added to latanoprost monotherapy. IOP measurements were taken every two hours in a sleep laboratory before and after four-week drug treatments. The overall results failed to support a high symmetry in the 24-hour IOP reductions between the two eyes with monotherapy or adjunctive therapy.
Given these findings, the authors suggest that working with the averages of multiple paired IOP responses may improve the strength of the association.
American Journal of Ophthalmology
In a retrospective case file review, Perera et al. studied the characteristics influencing treatment outcomes of allograft corneal rejection. They found that treatment failure is more likely to occur among patients with corneal neovascularization, large donor graft buttons and corneal edema at presentation.
The researchers reviewed those files containing first episodes of corneal allograft rejection in patients who underwent penetrating keratoplasty at the Royal Victorian Eye and Ear Hospital in Melbourne, Australia, from 1991 to 2006. Cases were divided into two groups based on the response to treatment for graft rejection: treatment responders and failures. Main parameters evaluated were demographic characteristics, preoperative clinical profile, donor characteristics, surgical technique, presentation and treatment of rejection episode.
A total of 235 cases of graft rejection were identified, of which 195 cases (83 percent) were successfully treated and 40 (17 percent) failed to respond. Age and gender were comparable in both groups. On univariate analysis, primary diagnosis of keratoconus and phakic lens status at the time of surgery were more common in treatment responders, whereas aphakic bullous keratopathy, history of glaucoma, aphakia and previous grafts were more common among treatment failures. Multivariate analysis revealed that preoperative corneal neovascularization, larger donor button size (greater than 9 mm) and corneal edema at presentation were independently associated with failure of treatment for graft rejection.
In a nonrandomized, prospective clinical study, Flemmons et al. evaluated iCare rebound tonometry in the home setting for documentation of diurnal IOP fluctuations in children. The researchers found that home tonometry was reliable, easily performed by caregivers and well tolerated; and it offered IOP information valuable in clinical management.
Pediatric ophthalmology clinic patients were recruited if they were able to cooperate with IOP measurement by iCare rebound tonometry and if the caregiver was willing and able to obtain iCare measurements at home. The caregiver was instructed on the use of the iCare tonometer. The patient’s IOP was measured by the caregiver at home at designated time periods for at least two consecutive days. The child’s IOP was measured first by iCare tonometry, followed by a second method (Goldmann applanation).
Seventeen children (17 eyes) with known or suspected glaucoma and 11 normal children were included in the study. Excellent reliability was obtained by caregivers in 70 percent of iCare measurements. The mean difference between iCare and Goldmann applanation in the clinic was 2 ± 4 mmHg. Daily IOP fluctuation occurred both in subjects with glaucoma and in normal subjects. In children with known or suspected glaucoma, relative peak and trough IOPs occurred in the early morning (45 percent) and late evening (43.5 percent), respectively.
Choudhury et al. evaluated the risk factors for four-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. They found that older age and higher pulse pressure were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen and retinal pigmentary abnormalities. In addition, the presence of clinically diagnosed diabetes was independently associated with increased retinal pigment, and male gender was associated with retinal pigment epithelial depigmentation. Older age and current smoking were independently associated with progression of AMD.
In this prospective cohort study, participants aged 40 or older from the Los Angeles Latino Eye Study (LALES) underwent standardized, comprehensive ophthalmologic examinations at baseline and at four years of followup. AMD was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD with baseline sociodemographic, behavioral, clinical and ocular characteristics.
In the Thessaloniki Eye Study, Topouzis et al.. evaluated the risk factors for primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG). They found that IOP was the only factor strongly associated with both conditions, whereas moderate-to-high myopia showed borderline significance in both. Vascular systemic diseases and their treatment were associated only with POAG.
This study included patients 60 years of age and older. Glaucomatous damage and presence of pseudoexfoliation were defined according to specific criteria. Subjects were classified as having POAG if they had glaucoma and an open, normal-appearing anterior chamber angle and the absence of other secondary causes of glaucoma in either eye. Subjects were classified as having PEXG if they had glaucoma and pseudoexfoliation in either eye. Openangle glaucoma (OAG) was considered to be the combination of POAG and PEXG. Subjects were classified as controls in the absence of glaucoma. OAG subjects were compared with controls; POAG subjects were compared with controls without pseudoexfoliation; and PEXG subjects were compared with controls with pseudoexfoliation. All assessments took demographic, lifestyle, ophthalmic and systemic factors into account.
In multivariate analysis restricted to persons who had at least one phakic eye and who participated in clinic visits, factors associated with higher odds for OAG included IOP, pseudoexfoliation, history of coronary artery bypass or vascular surgery, and moderate-tohigh myopia. In an analysis including all clinic visits, increased age became significantly associated as well. In multivariate analysis for POAG, associations were found for increased age, increased IOP, history of coronary artery bypass or vascular surgery, and history of diabetes treated with insulin. In multivariate analysis for PEXG, associations were found for increased IOP.
In a retrospective, longitudinal cohort study, Vanderbeek et al. compared the incidence, prevalence and hazard of nonexudative and exudative age-related macular degeneration among different racial groups in the United States. They found that racial minorities, including Latinos and Asian-Americans, had different risks of developing nonexudative and exudative AMD than did Caucasians.
The researchers reviewed the billing records of all encounters for 2,259,061 beneficiaries aged 41 and older who were enrolled in a large, national U.S. managed care network from 2001 through 2007. They then determined the incidence and prevalence of nonexudative and exudative AMD and stratified the results by race. Cox regression analyses determined the hazard of nonexudative and exudative AMD for each race, with adjustment for confounders.
During the study, 113,234 individuals (5 percent) were diagnosed with nonexudative and 17,181 (0.76 percent) with exudative AMD. After adjustment for confounders, African-Americans had a significantly reduced hazard of both types of AMD at age 60 and a reduced hazard of both types at age 80 relative to Caucasians. Similar comparisons for Latinos demonstrated an 18 percent reduced hazard for nonexudative AMD at age 80 relative to Caucasians. Asian-Americans showed a 28 percent increased hazard for nonexudative AMD at age 60 but a 46 percent decreased hazard for exudative AMD at age 80.
In a nationally representative longitudinal sample of Medicare patients, Day et al. determined the rates of ocular complications after anti-VEGF treatment for age-related macular degeneration (AMD). They found that rates of endophthalmitis, uveitis and vitreous hemorrhage were higher in the group treated with anti-VEGF injection than in the control group, although these complications were rare in both groups. The overall risk of severe ocular complications was significantly higher in the anti-VEGF treatment group.
Using a large sample of Medicare inpatient, outpatient, Part B and durable medical equipment claims files, the researchers identified diagnoses of AMD and anti-VEGF injections of ranibizumab, bevacizumab or pegaptanib from the International Classification of Diseases codes and Current Procedural Terminology procedure codes. They compared 6,154 individuals undergoing anti-VEGF treatment for AMD against 6,154 matched controls with AMD who did not undergo anti-VEGF treatment. Propensity score matching was used to match individuals receiving anti-VEGF injections with controls. Rates of postinjection adverse outcomes (endophthalmitis, rhegmatogenous retinal detachment, retinal tear, uveitis and vitreous hemorrhage) were analyzed by cumulative incidence and Cox proportional hazards model to control for demographic factors and ocular comorbidities.
At the two-year follow-up, the perinjection rates of endophthalmitis (0.09 percent), uveitis (0.11 percent) and vitreous hemorrhage (0.23 percent) were significantly higher in the anti-VEGF treatment group. With Cox proportional hazards modeling, the anti-VEGF treatment group had a 102 percent higher risk of severe ocular complications overall and a 4 percent increased risk per injection; these findings were both statistically significant.
Archives of Ophthalmology
Dev Borman et al. investigated the phenotype of a cohort of pediatric patients with autosomal recessive bestrophinopathy, a recently described condition caused by compound heterozygous mutations in BEST1. The authors found that the diagnostic features, results of electrophysiological studies and retinal imaging distinguish this condition from Best disease.
Six patients presenting at between 2 and 10 years of age from five unrelated Caucasian families participated in this retrospective case series. Subjects underwent complete ophthalmic examination, retinal imaging and ISCEV-standard electrophysiological assessment. Electro-oculography (EOG) was performed in available parents. Molecular analysis was undertaken for all coding regions and intron-exon boundaries of BEST1.
Visual acuity remained well preserved over the maximum follow-up period of 13 years, unless subretinal neovascularization developed. Funduscopy demonstrated characteristic bilateral subretinal yellow deposits. Fundus autofluorescence imaging displayed marked hyperautofluorescence corresponding to these lesions. OCT features included subretinal hyporeflective regions at the macula; discrete dome-shaped, hyperreflective subretinal elevations; and prominence of the photoreceptor outer segment layer. In the oldest patients, intraretinal cysts had developed in the inner retinal layers. The EOG light rise was undetectable in all patients tested but was normal in all available parents. Full-field electroretinograms were normal in the younger patients; however, the two oldest subjects demonstrated generalized photoreceptor dysfunction with macular involvement. All patients were found to have compound heterozygous mutations in BEST1.
Stein et al. assessed whether an association exists between geographic and climatic factors and exfoliation syndrome, the most common form of secondary open-angle glaucoma. They found that ambient temperature and sun exposure were the most important triggers.
Using longitudinal data obtained from a large, nationwide managed care network in the United States, the researchers studied 626,901 enrollees aged 60 and older to assess whether the risk of exfoliation syndrome differed among persons residing in central-tier, northern-tier and southern-tier states. They also examined whether climatic factors, such as levels of sunshine exposure, temperature and altitude, were associated with the syndrome.
In multivariable-adjusted Cox regression analyses, the researchers found that residents of northern-tier states had a 114 percent increased likelihood of developing exfoliation syndrome relative to persons living in middle-tier states. In contrast, residents of southern states had a 17 percent reduced hazard for the condition. In further analyses, residents of the upper Midwest were found to have a considerably elevated risk for exfoliation syndrome, compared with persons living in the centrally located state of Missouri.
Lambiase et al. evaluated tear levels of neuromediators in patients with dry eye and identified their correlation with clinical changes and disease severity. They found that decreased tear levels of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) in dry eye were related to impaired lacrimal function, while increased tear levels of nerve growth factor (NGF) were more closely related to corneal epithelial damage.
Nineteen patients with dry eye (10 non-Sjögren, five Sjögren and four ocular cicatricial pemphigoid patients) underwent complete ocular examination, lacrimal function tests and fluorescein staining. Dry eye severity was graded according to the Oxford score. Tear samples were collected, and substance P, CGRP, NPY, vasoactive intestinal peptide and NGF concentrations were evaluated and correlated to the clinical findings.
Results showed that dry eye patients had increased NGF and decreased CGRP and NPY tear levels. Dry eye severity correlated directly with NGF and inversely with CGRP and NPY. NGF also showed a direct correlation with conjunctival hyperemia and fluorescein staining, whereas CGRP directly correlated with Schirmer test values. Subgroup analysis revealed selective changes in tear levels of CGRP and NPY—but not NGF—in patients with autoimmune dry eye.
Rao et al. evaluated the structurefunction relationship in glaucoma using spectral-domain optical coherence tomography (SD-OCT). The strongest relationships using SDOCT were found for retinal nerve fiber layer (RNFL) measurements at arcuate areas and inner macular thickness measurements.
In a cross-sectional study, structure- function relationships were determined for all the participants in the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study who had undergone standard automated perimetry (SAP) and SD-OCT testing within six months of each other. The relationship was also evaluated using a linear model described by Hood and Kardon. The researchers analyzed 579 examinations from 80 eyes of 47 normal subjects, 199 eyes of 130 glaucoma suspects and 213 eyes of 146 glaucoma patients. R2 for the association between SAP total deviation and SD-OCT parameters ranged from 0.01 for the nasal rim area to 0.3 for the inferior inner macular thickness. The strongest structure-function associations were found for RNFL measurements at arcuate areas and inner macular thickness measurements. The linear model proposed by Hood and Kardon fitted the data well.
Christen et al. found that regular consumption of omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) and fish was associated with a significantly decreased risk of incident age-related macular degeneration in a large cohort of female health professionals and may be of benefit in primary prevention of AMD.
At baseline, a total of 38,022 women who did not have a diagnosis of AMD completed a food-frequency questionnaire. The study outcome was incident AMD that caused a reduction in visual acuity to 20/30 or worse based on participant self-reporting and confirmed by medical record review.
During an average of 10 years of follow-up, a total of 235 cases of AMD were confirmed. Most cases were characterized by some combination of drusen and retinal pigment epithelial changes. Compared with women in the lowest tertile for intake of docosahexaenoic acid, women in the highest tertile had a 38 percent reduced risk of AMD. For eicosapentaenoic acid, women in the highest tertile of intake had a 34 percent reduced risk. Regular intake of fish was associated with comparable reductions in risk.
In a retrospective case series, Missoi et al. evaluated the efficacy and adverse effects of oral propranolol for treatment of periocular infantile hemangioma. They found that the treatment was effective in all study patients, with a mean 33 percent reduction in astigmatism and a 39 percent reduction in hemangioma surface area.
Seventeen children with infantile hemangioma were treated with oral propranolol three times daily, with outpatient monitoring of adverse effects. The starting dosage was 0.5 mg/ kg/day for one week, 1 mg/kg/day for the following week and 2 mg/kg/day for the remaining duration of treatment. Amblyopia was treated with part-time occlusion therapy. Treatment was tapered after age 1 or when the treatment response reached a plateau.
Nineteen periocular hemangiomas from 17 children were studied. Treatment with oral propranolol reduced the size of all hemangiomas. Median posttreatment surface area was 61 percent of the original size. Mild rebound growth that did not necessitate retreatment was found in two patients. One patient experienced a benign episode of bradycardia. Seven patients had amblyopia. Vision equalized in all but one child, who received ongoing amblyopia therapy.
Roundup of Other Journals
Through a genome-wide association replication study, Shi et al. have identified a genetic susceptibility locus for high myopia in a Han Chinese population. The authors’ findings serve a twofold purpose: they help reveal the genetic basis of high myopia, and they indicate the existence of genetic heterogeneity of disease susceptibility among different ethnic populations.
The authors analyzed a Shanghai Han Chinese dataset of 419 unrelated individuals with high myopia from the Shanghai and Anhui regions and 669 unrelated normal controls. The investigators identified a significant association between high myopia and a variant at 13q12.12 (rs9318086). In addition, five other single-nucleotide polymorphisms in the same linkage disequilibrium block with rs9318086 proved to be significantly associated with high myopia in the Han Chinese population.
Raz et al. investigated why patients complain of continued visual problems long after recovery from an acute attack of optic neuritis (ON). They discovered that a sustained motion-perception deficit persists following an attack, even when a patient’s static visual functions have recovered.
In this study, the authors followed 21 patients with unilateral, first-ever ON for a year. They utilized a novel set of motion-perceptual tasks to test dynamic visual deficits and found that while the affected eyes had returned to normal static performance levels, motion perception continued to be impaired throughout the 12-month follow-up period.
In an accompanying editorial, Charles J. Duffy notes that these findings may be traced to the parallel pathways that originate in the retina and extend throughout the cerebral cortex to facilitate the separate processing of visual form and motion. He supports both of the hypotheses presented by the authors to explain the more prolonged motion-processing impairments in ON: first, that the greater impact of the acute phase on motion processing may result in greater long-term motion impairments compared with form impairments; and, second, ONrelated impairment recovery might occur less completely and more slowly for motion processing as compared with form processing.
According to a JAMA commentary by Dyrbye and Shanafelt, one key issue that has not been addressed during the national health care debate is physician burnout. The authors contend that physician stress may represent a significant barrier to implementing the Patient Protection and Affordable Care Act. Some factors that may lead to physician burnout include excessive work hours and on-call responsibilities, an inability to balance work and personal time, a lack of control at work and a decrease in autonomy. Implementation of current legislation may cause more stress, as providing insurance to 30 million Americans who previously did not have insurance will no doubt translate into greater demand for care in a system already trying to cope with an increasing older population and a decreasing supply of physicians.
The authors recognize some positive aspects of the new legislation, including the removal of insurance barriers in treating preexisting conditions, assistance for medication coverage and simplification of insurance claims, including the introduction of a standardized claim form. Although these steps are important, efforts must be made to identify and deal with factors that contribute to job dissatisfaction among physicians to avoid the possibility of physician burnout.
Oh et al. used spectral-domain optical coherence tomography (SD-OCT) to gain insight into the retinal changes in areas of commotio retinae, which is characterized by transient opacity at the level of the deep sensory retina. They found that retinal opacity typical of commotio retinae corresponded to a hyperreflective outer segment in the OCT without any change in retinal thickness, demonstrating clinically what was previously described on histopathologic examination.
SD-OCT is designed to allow for segmentation of the retinal pigment epithelium (RPE) and Bruch’s membrane. In this retrospective, observational case series, the authors used this technology to study 14 eyes of 14 patients who had experienced a high-impact blunt injury, without a penetrating wound, resulting in various types of injuries to the eyeball. They performed the SD-OCT on the same day as the injury, comparing the retinal thickness and volume of eyes with commotio retinae to those of eyes without it.