Ophthalmology

Editorial Board

2014-03-01

This Issue At A Glance

Jean Shaw, John Kerrison — 2014-03-01

In the largest study of the issue to date, Bertelsen et al (p. 637) evaluated the mortality rate of patients with central retinal vein occlusion (CRVO). They found that CRVO was associated with an overall increase in mortality and that the increase could be attributed to cardiovascular and cerebrovascular disease. For this registry-based study, Danish researchers evaluated 439 patients with CRVO and 2195 age- and gender-matched controls. Over a mean follow-up period of 5.1 years for the CRVO patients and 5.7 years for the controls, the overall mortality rate was 5.9 deaths/100 person years for the CRVO patients and 4.3 deaths/100 person years for the controls. In addition, CRVO patients were at increased risk of developing peripheral artery disease, congestive heart failure, ischemic heart disease and myocardial infarction, and cerebrovascular disease. Given this association, the researchers recommended that CRVO patients be treated for such conditions as hypertension and diabetes and, if needed, be referred to a primary care physician.

A Simple Vista en Este Número

Jean Shaw, John Kerrison — 2014-03-01

En el estudio más largo que se haya realizado hasta la fecha, Bertelsen y otros (p. 637) evaluaron la tasa de mortalidad de pacientes con oclusión de la vena central de la retina (CRVO). Encontraron que la CRVO se asociaba con un incremento general en la mortalidad y que ese incremento podría atribuirse a enfermedad cardiovascular y cerebrovascular. Para este estudio, basado en un registro, los investigadores daneses evaluaron 439 pacientes con CRVO y 2195 controles equiparados para edad y género. Durante un período medio de seguimiento de 5,1 años para los pacientes de CRVO y 5,7 años para los controles, la tasa de mortalidad global fue de 5,9 muertes/100 personas año para los pacientes de CRVO y 4,3 muertes/100 personas año para los controles. Además, los pacientes con CRVO mostraron un mayor riesgo de desarrollar enfermedad arterial periférica, insuficiencia cardiaca congestiva, enfermedad cardiaca isquémica e infarto del miocardio, así como enfermedad cerebrovascular. Dada esta asociación, los investigadores recomendaron que los pacientes con CRVO fueran tratados para afecciones como hipertensión y diabetes y que, de ser necesario, fueran remitidos a un médico de atención primaria.

期刊一览

Jean Shaw, John Kerrison — 2014-03-01

在一项迄今为止最大型的研究中，Bertelsen (p. 637) 等人评估了视网膜中央静脉阻塞(CRVO)患者的死亡率。他们发现CRVO与总死亡率提高有密切关系，而这种提高又归因于心血管及脑血管疾病。在这项基于注册表的研究中，丹麦的研究人员分析了439名CRVO患者及2195名年龄及性别相对应的对照组。CRVO组平均观察时间为5.1年，对照组为5.7年，总死亡率CRVO组为5.9/100人年数，对照组为4.3/100人年数。另外，CRVO患者具有高患病风险，如外周动脉疾病，充血性心衰，缺血性心脏病及心肌梗塞，脑血管疾病。基于这种关系，研究人员建议CRVO患者应予以高血压及糖尿病治疗，甚至需要内科医生系统治疗。

2014-03-01

NEI's Audacious Goals Initiative

Rebecca J. Salowe, Joan M. O'Brien — 2014-03-01

In 2013, the National Eye Institute (NEI) launched a program with an unconventional goal. The NEI challenged the ophthalmic and vision research community to seek creative and pioneering initiatives that would fundamentally advance research over the next 10 to 15 years. The response was overwhelming, with >500 researchers and clinicians submitting ideas.

A Close Look at Pediatric Eye Disease

Michael X. Repka — 2014-03-01

The prevalence of visually significant and treatable eye disorders among children is much lower than the rate reported for adults. However, when there is a cost-effective intervention, the gain in quality of life will extend over many years. This premise is consistent with one of the vision objectives of Health People 2020, a national strategic plan developed by the United States Department of Health and Human Services: to reduce the prevalence of visual impairment in children. To assess the value of programs for prevention, detection, and treatment of visual impairment in children, as well as to design future interventions, it is necessary to know the prevalence of pediatric eye disease. Even better would be data describing any differences among identifiable subgroups of that population. Such differences could be present because of demographic and clinical characteristics, such as race or ethnicity or gender. Additionally, prevalence data affords the opportunity to assess differences in groups based on social, economic, and environmental disadvantages. Differences in health caused by such factors often are termed health disparities or inequalities.

Ophthalmic Patient Data Registries: Defining and Improving Quality and Outcomes

Sahar Kohanim, Paul Sternberg — 2014-03-01

Two articles in this issue of Ophthalmology (see articles on pages 637 and 643) highlight the importance of registries and the wealth of data that they can provide. In the first, Jackson et al used the United Kingdom National Ophthalmology Database to study real-life surgeon procedure choices, complication rates, and reoperation rates for primary retinal detachment repair and suggest that this information may assist vitreoretinal surgeons in benchmarking their own rates. In the second article, Bertelsen et al from Denmark cross-referenced multiple Danish national registries to perform a registry-based case-control study assessing mortality and comorbidities in patients with and without central retinal vein occlusion. They found that, although mortality was increased in patients with central retinal vein occlusion, this could be accounted for mostly by the patients' pre-existing comorbidities.

Risk Factors for Amblyopia in the Vision in Preschoolers Study

2013-10-21

Objective: To evaluate risk factors for unilateral amblyopia and for bilateral amblyopia in the Vision in Preschoolers (VIP) study.Design: Multicenter, cross-sectional study.Participants: Three- to 5-year-old Head Start preschoolers from 5 clinical centers, overrepresenting children with vision disorders.Methods: All children underwent comprehensive eye examinations, including threshold visual acuity (VA), cover testing, and cycloplegic retinoscopy, performed by VIP-certified optometrists and ophthalmologists who were experienced in providing care to children. Monocular threshold VA was tested using a single-surround HOTV letter protocol without correction, and retested with full cycloplegic correction when retest criteria were met. Unilateral amblyopia was defined as an interocular difference in best-corrected VA of 2 lines or more. Bilateral amblyopia was defined as best-corrected VA in each eye worse than 20/50 for 3-year-olds and worse than 20/40 for 4- to 5-year-olds.Main Outcome Measures: Risk of amblyopia was summarized by the odds ratios and their 95% confidence intervals estimated from logistic regression models.Results: In this enriched sample of Head Start children (n = 3869), 296 children (7.7%) had unilateral amblyopia, and 144 children (3.7%) had bilateral amblyopia. Presence of strabismus (P < 0.0001) and greater magnitude of significant refractive errors (myopia, hyperopia, astigmatism, and anisometropia; P < 0.00001 for each) were associated independently with an increased risk of unilateral amblyopia. Presence of strabismus, hyperopia of 2.0 diopters (D) or more, astigmatism of 1.0 D or more, or anisometropia of 0.5 D or more were present in 91% of children with unilateral amblyopia. Greater magnitude of astigmatism (P < 0.0001) and bilateral hyperopia (P < 0.0001) were associated independently with increased risk of bilateral amblyopia. Bilateral hyperopia of 3.0 D or more or astigmatism of 1.0 D or more were present in 76% of children with bilateral amblyopia.Conclusions: Strabismus and significant refractive errors were risk factors for unilateral amblyopia. Bilateral astigmatism and bilateral hyperopia were risk factors for bilateral amblyopia. Despite differences in selection of the study population, these results validated the findings from the Multi-Ethnic Pediatric Eye Disease Study and Baltimore Pediatric Eye Disease Study.

Prevalence of Vision Disorders by Racial and Ethnic Group among Children Participating in Head Start

2013-11-01

Objective: To compare the prevalence of amblyopia, strabismus, and significant refractive error among African-American, American Indian, Asian, Hispanic, and non-Hispanic white preschoolers in the Vision In Preschoolers study.Design: Multicenter, cross-sectional study.Participants: Three- to 5-year old preschoolers (n = 4040) in Head Start from 5 geographically disparate areas of the United States.Methods: All children who failed the mandatory Head Start screening and a sample of those who passed were enrolled. Study-certified pediatric optometrists and ophthalmologists performed comprehensive eye examinations including monocular distance visual acuity (VA), cover testing, and cycloplegic retinoscopy. Examination results were used to classify vision disorders, including amblyopia, strabismus, significant refractive errors, and unexplained reduced VA. Sampling weights were used to calculate prevalence rates, confidence intervals, and statistical tests for differences.Main Outcome Measures: Prevalence rates in each racial/ethnic group.Results: Overall, 86.5% of children invited to participate were examined, including 2072 African-American, 343 American Indian (323 from Oklahoma), 145 Asian, 796 Hispanic, and 481 non-Hispanic white children. The prevalence of any vision disorder was 21.4% and was similar across groups (P = 0.40), ranging from 17.9% (American Indian) to 23.3% (Hispanic). Prevalence of amblyopia was similar among all groups (P = 0.07), ranging from 3.0% (Asian) to 5.4% (non-Hispanic white). Prevalence of strabismus also was similar (P = 0.12), ranging from 1.0% (Asian) to 4.6% (non-Hispanic white). Prevalence of hyperopia >3.25 diopter (D) varied (P = 0.007), with the lowest rate in Asians (5.5%) and highest in non-Hispanic whites (11.9%). Prevalence of anisometropia varied (P = 0.009), with the lowest rate in Asians (2.7%) and highest in Hispanics (7.1%). Myopia >2.00 D was relatively uncommon (<2.0%) in all groups with the lowest rate in American Indians (0.2%) and highest rate in Asians (1.9%). Prevalence of astigmatism >1.50 D varied (P = 0.01), with the lowest rate among American Indians (4.3%) and highest among Hispanics (11.1%).Conclusions: Among Head Start preschool children, the prevalence of amblyopia and strabismus was similar among 5 racial/ethnic groups. Prevalence of significant refractive errors, specifically hyperopia, astigmatism, and anisometropia, varied by group, with the highest rate of hyperopia in non-Hispanic whites, and the highest rates of astigmatism and anisometropia in Hispanics.

Mortality in Patients with Central Retinal Vein Occlusion

2013-09-18

Purpose: To assess mortality in patients with central retinal vein occlusion (CRVO).Design: Registry-based cohort study.Participants and Controls: Four hundred thirty-nine photographically verified CRVO patients and a control cohort of 2195 unexposed subjects matched by age and gender and alive on the date CRVO was diagnosed in the corresponding case.Methods: Data from nationwide registries were used to compare mortality rates in CRVO patients with a control cohort over a mean follow-up of 5.1 years for cases and of 5.7 years for controls.Main Outcome Measures: Hazard ratios (HRs) obtained by Cox regression and standardized mortality ratios (SMRs) stratified by age and gender served as measures of relative mortality risk.Results: Mortality was higher in patients with CRVO (HR, 1.45; 95% confidence interval [CI], 1.19–1.76) than in the control cohort, adjusted for age, gender, and time of diagnosis. Mortality was comparable between the 2 groups (HR, 1.19; 95% CI, 0.96–1.46) when adjusting for overall occurrence of cardiovascular disease and diabetes. Subgroup analysis found that the age-stratified mortality rate was increased significantly in the total group of men (SMR, 1.27; 95% CI, 1.03–1.56) and in women 60 to 69 years of age (SMR, 1.94; 95% CI, 1.22–3.08).Conclusions: Central retinal vein occlusion was associated with an overall increase in mortality compared with controls that was attributed statistically to cardiovascular disorders and diabetes. We recommend treatment of hypertension and diabetes, if present, and referral of patients found to have CRVO who are not already being treated by a primary care physician.

United Kingdom National Ophthalmology Database Study of Vitreoretinal Surgery: Report 3, Retinal Detachment

2013-08-26

Purpose: To describe rhegmatogenous retinal detachment (RD) surgery.Design: National Ophthalmology Database study.Participants: A total of 3403 eyes from 3321 patients undergoing primary RD surgery.Methods: Participating centers prospectively collected clinical data using a single electronic medical record system, with automatic extraction of anonymized data to a national database, from 2002 to 2010.Main Outcome Measures: Description of the primary procedures performed, intraoperative complication rate, and proportion of eyes undergoing subsequent RD or cataract surgery. We undertook an exploratory analysis of change in visual acuity (VA) using the data available.Results: Of 3403 operations, 2693 (79.1%) were pars plana vitrectomy (PPV), 413 (12.1%) were retinopexy with a scleral buckle (SB), and 297 (8.7%) were PPV with an SB (PPV-SB). For PPV and PPV-SB, 18.8% were with hexafluoroethane, 12.1% were with perfluoropropane, 43.1% were with sulfahexafluoride, 1.8% were with air, 17.9% were with silicone oil, and 10.7% were with cataract surgery. Within 1 year of vitrectomy, 52.1% of phakic eyes had undergone cataract surgery. For all RD operations combined (and excluding cataract surgery complications), 5.1% had 1 or more intraoperative complication, 13.0% underwent further RD surgery, and 8.3% had silicone oil in situ at last review. The RD reoperation rate was 13.3%, 12.3%, and 14.5% for PPV, SB, and PPV-SB, respectively. For 961 eyes with a baseline and final VA measurement, the median presenting logarithm of the minimum angle of resolution VA improved from 1.0 to 0.5 (20/200–20/63) after a median follow-up of 0.6 years.Conclusions: These results may help vitreoretinal surgeons to benchmark their intraoperative complication rate and reoperation rate and to compare their surgical techniques with their peers'. They suggest that the benefits of RD surgery greatly outweigh the risks.

Vitrectomy with Internal Limiting Membrane Peeling versus No Peeling for Idiopathic Full-Thickness Macular Hole

2013-12-04

Objective: To determine whether internal limiting membrane (ILM) peeling improves anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery when compared with the no-peeling technique.Design: Systematic review and individual participant data (IPD) meta-analysis undertaken under the auspices of the Cochrane Eyes and Vision Group. Only randomized controlled trials (RCTs) were included.Participants and Controls: Patients with idiopathic stage 2, 3, and 4 FTMH undergoing vitrectomy with or without ILM peeling.Intervention: Macular hole surgery, including vitrectomy and gas endotamponade with or without ILM peeling.Main Outcome Measures: Primary outcome was best-corrected distance visual acuity (BCdVA) at 6 months postoperatively. Secondary outcomes were BCdVA at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12 months; primary (after a single surgery) and final (after >1 surgery) macular hole closure; need for additional surgical interventions; intraoperative and postoperative complications; patient-reported outcomes (PROs) (EuroQol-5D and Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness.Results: Four RCTs were identified and included in the review. All RCTs were included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs. No evidence of a difference in BCdVA at 6 months was detected (mean difference, −0.04; 95% confidence interval [CI], −0.12 to 0.03; P = 0.27); however, there was evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean difference, −0.09; 95% CI, −0.17 to −0.02; P = 0.02). There was evidence of an effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95% CI, 4.98–17.24; P < 0.00001) and final macular hole closure (OR, 3.99; 95% CI, 1.63–9.75; P = 0.02) and less requirement for additional surgery (OR, 0.11; 95% CI, 0.05–0.23; P < 0.00001), with no evidence of a difference between groups with regard to intraoperative or postoperative complications or PROs. The ILM peeling was found to be highly cost-effective.Conclusions: Available evidence supports ILM peeling as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.

Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials

2013-12-04

Objective: To describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).Design: Prospective cohort study within a randomized clinical trial.Participants: Patients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).Methods: Eyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation.Main Outcome Measures: Scar formation.Results: Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4–3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1–1.8), foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7–3.6) versus <120 μm, foveal subretinal tissue complex thickness >275 μm (aHR, 2.4; CI, 1.7–3.6) versus ≤75 μm, foveal subretinal fluid (aHR, 1.5; CI, 1.1–2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3–2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5–0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars.Conclusions: Approximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar.

Genetic Susceptibility, Dietary Antioxidants, and Long-Term Incidence of Age-Related Macular Degeneration in Two Populations

2013-12-02

Objective: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk.Design: Pooled data analysis of population-based cohorts.Participants: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS).Methods: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], β-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses.Main Outcome Measures: All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale.Results: In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P = 0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P = 0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between β-carotene or vitamin C and genetic risk status.Conclusions: Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.

Comparison of Outcomes from a Phase 3 Study of Age-Related Macular Degeneration with a Matched, Observational Cohort

2013-12-02

Objective: To compare outcomes of intravitreal therapy from an observational study cohort with those of participants receiving treatment in the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab (MARINA) for the treatment of neovascular age-related macular degeneration (wet AMD).Design: Database observational study. Participants in the observational cohort were chosen to match demographic features and entry criteria of the treatment group from MARINA. Outcomes over 12 months were compared.Participants: Eight hundred twenty-one anti–vascular endothelial growth factor (anti-VEGF)-naïve eyes treated with ranibizumab with 12 months or more of follow-up were included in the total Fight Retinal Blindness! (FRB-All) cohort, whereas a subset of this cohort of 401 eyes who were matched to the MARINA treatment group were included as the FRB-MARINA cohort.Intervention: Intravitreal ranibizumab therapy of 0.5 mg for wet AMD.Methods: Visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters and treatments given were recorded continuously and anonymously in an electronic database for 12 months. Locally weighted scatterplot smoothing (LOESS) regression was used to plot change in visual acuity data over the course of 12 months for both the FRB-All cohort and the FRB-MARINA cohort, whereas results from the MARINA trial were taken from the published study report.Main Outcome Measures: Change in VA in logMAR letters over 12 months, treatment, and visit intensity.Results: Mean visual acuity improvement after 12 months in FRB-MARINA (+5.5 letters) was similar to that of the 0.5-mg group from MARINA (+7.2 letters). Improvement in FRB-ALL was slightly less (+4.9 letters). Mean treatment effect compared with the MARINA control group was similar for the MARINA treated group (+17.6 letters) and the FRB-MARINA cohort (+15.9 letters). A mean of 7.3 injections in 12 months was received by the observational cohorts.Conclusions: Similarity of mean VA improvement in the matched observational cohort with that of the phase 3 clinical trial suggests that these results can be achieved in real-world clinical practice with a modified treatment regimen.

RADIANCE: A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization Secondary to Pathologic Myopia

2013-12-09

Objective: To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV).Design: Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study.Participants: Patients (N = 277) with visual impairment due to myopic CNV.Methods: Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n = 116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55).Main Outcome Measures: Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months.Results: Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P < 0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P < 0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred.Conclusions: Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV.

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration: The COMPLETE Study

2013-11-27

Purpose: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD).Design: Prospective, double-masked, randomized clinical trial.Participants: Patients with GA measuring from 1.25 to 18 mm2 based on spectral-domain optical coherence tomography imaging.Methods: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores.Main Outcome Measures: Change in area of GA at 26 weeks.Results: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55±0.94 and 2.02±0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19±0.12 and 0.18±0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37±0.22 mm in the eculizumab-treated eyes and by a mean of 0.37±0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified.Conclusions: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Histopathology of Streptococcus Mitis/Oralis Endophthalmitis after Intravitreal Injection with Bevacizumab: A Report of 7 Patients

Jared L. Matthews, Sander R. Dubovy, Roger A. Goldberg, Harry W. Flynn — 2014-01-17

Purpose: To report the histopathologic findings of a series of patients from an outbreak of Streptococcal endophthalmitis after intravitreal injection of bevacizumab prepared by a single compounding pharmacy.Design: Case series.Participants: Seven surgical specimens (5 enucleated globes and 2 evisceration specimens) from 7 patients with endophthalmitis after intravitreal injection of bevacizumab.Methods: Retrospective case series, including clinical data and histopathologic specimens examined by light microscopy.Main Outcome Measures: Review of clinical data included baseline visual acuity, clinical intervention, and time elapsed from injection to loss of globe. Histopathologic specimens were reviewed for pathologic changes at all tissue levels.Results: Seven of 12 total patients (4 women, 3 men; mean age, 77.7 years) from an outbreak of Streptococcus mitis/oralis endophthalmitis after bevacizumab injection ultimately sustained loss of the affected globe, with an average of 139.1 days elapsed between injection and globe loss. Mean time from injection to presentation was 2.86 days (range, 1–6), and all patients were initially treated with vitreous tap and injection. Although histologic review of surgical specimens disclosed a wide range of pathologic tissue changes, recurring patterns of tissue damage were evident. All 5 enucleated globes displayed retinal detachment, fibrous proliferation with cyclitic membrane formation, rubeosis iridis, and secondary angle closure. All 7 specimens displayed persistent choroidal inflammation, in 1 case 208 days after injection. Six of 7 specimens had foci of retinal necrosis. Although vitreous cultures were positive in all cases, no organisms were identified by light microscopy in any of the 7 specimens.Conclusions: S. mitis/oralis endophthalmitis is a devastating complication of intravitreal injection with bevacizumab with a high rate of globe loss (7 of 12 patients, 58.3%) and a wide variety of severe pathologic tissue changes. Although no organisms were identified in the examined tissues, persistent inflammation was present in all cases, and fibrous proliferation resulted in cyclitic membrane formation and retinal detachment in all enucleated globes. These findings suggest that potential globe-salvaging interventions must address a pattern of changes involving persistent, chronic inflammation and fibrovascular proliferation as key components.

The Spectrum of Ocular Alterations in Patients with β-Thalassemia Syndromes Suggests a Pathology Similar to Pseudoxanthoma Elasticum

2013-12-04

Purpose: To determine the prevalence and spectrum of ocular fundus abnormalities in patients with β-thalassemia and to investigate risk factors for their development.Design: Cross-sectional, observational study.Participants: A total of 255 patients with β-thalassemia major (TM) and β-thalassemia intermedia (TI) were consecutively recruited and investigated.Methods: Patients underwent best correct visual acuity, indirect ophthalmoscopy, and fundus photography, including fundus autofluorescence (FAF) and near-infrared reflectance imaging using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters were determined, including mean ferritin levels, aspartate amino transferase, alanine amino transferase, calcium, pre-transfusion hemoglobin, history of splenectomy, and liver iron concentration. Factors associated with the ocular phenotype were assessed using logistic regression.Main Outcome Measures: Ocular phenotype as determined by clinical examination and used multimodal imaging.Results: A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%) affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau d'orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%), and optic disc drusen (2.0%). Pseudoxanthoma elasticum–like changes were more frequent in patients with TI (P < 0.001). Patients with PXE-like fundus changes were older than patients without these fundus changes (P < 0.001). In both patients with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest association with presence of PXE-like fundus changes in multivariate analyses. A total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity independently of the PXE-like fundus changes, which was associated with aspartate amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P = 0.005).Conclusions: Pseudoxanthoma elasticum–like fundus changes are a frequent finding in patients with β-thalassemia. In TI, these changes increase with duration or severity of the disease. This particular ocular phenotype suggests an ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional disease manifestation independent of the PXE-like syndrome. Patients with long-standing disease requiring iron-chelating treatment and a history of splenectomy need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.

En Face Enhanced-Depth Swept-Source Optical Coherence Tomography Features of Chronic Central Serous Chorioretinopathy

2013-11-27

Objective: To characterize en face features of the retinal pigment epithelium (RPE) and choroid in eyes with chronic central serous chorioretinopathy (CSCR) using a high-speed, enhanced-depth swept-source optical coherence tomography (SS-OCT) prototype.Design: Consecutive patients with chronic CSCR were prospectively examined with SS-OCT.Participants: Fifteen eyes of 13 patients.Methods: Three-dimensional 6×6 mm macular cube raster scans were obtained with SS-OCT operating at 1050 nm wavelength and 100 000 A-lines/sec with 6 μm axial resolution. Segmentation of the RPE generated a reference surface; en face SS-OCT images of the RPE and choroid were extracted at varying depths every 3.5 μm (1 pixel). Abnormal features were characterized by systematic analysis of multimodal fundus imaging, including color photographs, fundus autofluorescence, fluorescein angiography, and indocyanine-green angiography (ICGA).Main Outcome Measures: En face SS-OCT morphology of the RPE and individual choroidal layers.Results: En face SS-OCT imaging at the RPE level revealed absence of signal corresponding to RPE detachment or RPE loss in 15 of 15 (100%) eyes. En face SS-OCT imaging at the choriocapillaris level showed focally enlarged vessels in 8 of 15 eyes (53%). At the level of Sattler's layer, en face SS-OCT documented focal choroidal dilation in 8 of 15 eyes (53%) and diffuse choroidal dilation in 7 of 15 eyes (47%). At the level of Haller's layer, these same features were observed in 3 of 15 eyes (20%) and 12 of 15 eyes (80%), respectively. In all affected eyes, these choroidal vascular abnormalities were seen just below areas of RPE abnormalities. In 2 eyes with secondary choroidal neovascularization (CNV), distinct en face SS-OCT features corresponded to the neovascular lesions.Conclusions: High-speed, enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization of pathologic features of the RPE and choroid in eyes with chronic CSCR not usually appreciated with standard spectral domain (SD) OCT. En face SS-OCT imaging seems to be a useful tool in the identification of CNV without the use of angiography. This in vivo documentation of the RPE and choroidal vasculature at variable depths may help elucidate the pathophysiology of disease and can contribute to the diagnosis and management of chronic CSCR.

Driving Habits in Older Patients with Central Vision Loss

2013-12-02

Objective: To determine if central visual loss is associated with driving cessation, driving restriction, or other-driver preference.Design: Cross-sectional study.Participants: Sixty-four subjects with bilateral visual loss (<20/32 in better eye) or severe unilateral visual loss (<20/200) from age-related macular degeneration (AMD) and 58 normally sighted controls between 60 and 80 years of age.Methods: Participants self-reported driving habits. Other-driver preference was defined as preferring that another drive when there is more than 1 driver in the car. Subjects reporting 2 or more driving limitations were considered to have restricted their driving.Main Outcome Measures: Self-reported driving cessation, other-driver preference, and driving restriction.Results: Age-related macular degeneration subjects were older (74.7 vs. 69.7 years), had worse visual acuity (VA; mean better-eye VA, 0.43 vs. 0.08 logarithm of minimum angle of resolution [logMAR]) and contrast sensitivity (CS; 1.4 vs. 1.9 log units of CS [logCS]), and were more likely to be white when compared with controls (P < 0.001 for all). Drivers with AMD-related vision loss were more likely to avoid driving over longer distances, beyond 1 hour, at night, and in unfamiliar conditions (P < 0.05 for all). In multivariate models, driving cessation was associated with worse better-eye VA (odds ratio [OR], 1.5 per 1-line decrement in VA; P < 0.001) and worse binocular CS (OR, 1.36 per 0.1 logCS increment; P = 0.005); however, AMD group status was not associated with driving cessation (OR, 1.9; P = 0.35). Factors predicting driving restriction were AMD (OR, 9.0; P = 0.004), worse vision (OR, 2.5 per line of VA loss; P < 0.001), lower CS (OR, 2.2 per 0.1-logCS increment; P < 0.001), and female gender (OR, 27.9; P = 0.002). Other-driver preference was more common with worse vision (OR, 1.6 per 0.1-logMAR increment; P = 0.003), female gender (OR, 4.5; P = 0.02), and being married (OR, 3.8; P = 0.04).Conclusions: Most patients with AMD-related central vision loss continue to drive, but demonstrate significant driving restrictions, especially with more severe VA and CS loss. Future work should determine which driving adaptations the visually impaired best balance safety and independence.

Association between Visual Field Defects and Quality of Life in the United States

Mary Qiu, Sophia Y. Wang, Kuldev Singh, Shan C. Lin — 2013-12-16

Purpose: To investigate the association between visual field defects and quality of life in the United States population.Design: Cross-sectional study.Participants: A total of 5186 participants in the 2005 through 2008 National Health and Nutrition Examination Survey 40 years of age and older without a self-reported history of age-related macular degeneration or prior refractive surgery who had undergone frequency doubling technology perimetric testing.Methods: Frequency doubling technology perimetry was performed in both eyes. Results from the better eye were used to categorize subjects as normal or having mild, moderate, or severe visual field loss. Subjects completed surveys about their visual and physical functioning ability.Main Outcome Measures: Disability pertaining to 6 vision-related activities, 2 visual function questions, and 5 physical functioning domains.Results: Eighty-one percent of subjects had normal visual fields and 10%, 7%, and 2% demonstrated mild, moderate, and severe visual field defects, respectively. Subjects with greater severity of visual field defects had greater difficulty with vision-related activities. Subjects with severe visual field defects demonstrated the greatest odds of difficulty with all 6 activities. The 2 activities impacted most adversely were daytime driving in familiar places (odds ratio [OR], 12.4; 95% confidence interval [CI], 6.1–25.1) and noticing objects off to the side when walking (OR, 7.7; 95% CI, 4.7–12.7). Subjects with severe visual field defects had greater odds of worrying about eyesight (OR, 3.4; 95% CI, 2.0–5.8) and being limited by vision in the time spent on daily activities (OR, 5.1; 95% CI, 3.0–8.5). Subjects with severe visual field defects demonstrated the greatest odds of difficulty with 3 physical function domains, including activities of daily living (OR, 2.45; 95% CI, 1.37–4.38), instrumental activities of daily living (OR, 2.45; 95% CI, 1.37–4.38), as well as leisure and social activities (OR, 3.29; 95% CI, 1.87–5.77).Conclusions: Greater severity of visual field abnormality was associated with significantly greater odds of disability with vision-related function and physical function. These findings support the necessity of routine screening to find those who may benefit from therapy to prevent progressive glaucomatous vision loss.

Defining 10-2 Visual Field Progression Criteria: Exploratory and Confirmatory Factor Analysis Using Pointwise Linear Regression

2013-12-02

Purpose: To test different visual field progression criteria using trend analysis in a glaucoma population followed with long sequences of 10-2 tests as a first attempt to understand and document rates of progression in the central field.Design: Retrospective cohort study.Participants: We included 146 eyes of 146 patients with established glaucoma.Methods: Pointwise linear regression analysis using the methods of ordinary least squares was performed on the 68 test locations of the 10-2 visual field sequences. Threshold sensitivities at each test location were plotted as the dependent variable against follow-up time as the independent variable. Statistically significant progression or improvement of a visual field test point was defined if its regression slope measured ≤−1.0 dB/year or ≥+1.0 dB/year, respectively, at P < 0.01. We explored sets of criteria to define visual field progression, generating a hypothetical sensitivity (progression), specificity (improvement), and progression-to-improvement ratio (PIR) for each criterion. The criterion with the highest PIR was deemed the one with best performance. Latent class analysis (LCA) was used to determine visual field sectors with highest inter-correlation.Main Outcome Measures: The performance of different visual field progression criteria to detect fast rates of mean deviation (MD) change.Results: Median baseline 10-2 MD value was −12.0 dB (interquartile range [IQR], −6.7 to −17.8 dB), and the median rate of 10-2 MD change over time was −0.38 dB/year (IQR, −0.07 to −0.77 dB/year). The highest PIR was obtained with the progression criterion requiring at least 3 test points located in the same LCA-derived 10-2 visual field sector progressing faster than −1.0 dB/year at P < 0.01. This criterion was further validated for content and convergence.Conclusions: This is the first study to investigate progression criteria for 10-2 visual fields using rates of change and to test their performance and validity. These findings may be useful to improve the monitoring of patients with glaucoma at different levels of functional loss and to develop new perimetric algorithms that scrutinize specific visual field locations for a more accurate detection of progression.

Retinal Blood Flow in Glaucomatous Eyes with Single-Hemifield Damage

2013-12-02

Purpose: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere.Design: Prospective, nonrandomized, case-control study.Participants: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls.Methods: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed.Main Outcome Measures: Total and hemispheric RS, RBF, RNFL, and GCC values.Results: The total RBF (34.6±12.2 μl/minute) and venous cross-sectional area (0.039±0.009 mm2) were reduced (P < 0.001) in those with glaucoma compared with controls (46.5±10.6 μl/minute; 0.052±0.012 mm2). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3±5.4 vs. 19.3±8.4 μl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0±20.2 vs. 103.7±20.6 μm, P = 0.002; 77.6±12.1 vs. 83.6±10.1 μm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3±8.4 μl/minute), RNFL (103.7±20.6 μm), and GCC (83.6±10.1 μm) were reduced (P < 0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2±5.3 μl/minute, 124.8±9.6 μm, and 96.1±5.7 μm, respectively).Conclusions: In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.

The Ability of Healthy Volunteers to Simulate a Neurologic Field Defect on Automated Perimetry

Deepta Ghate, Brian Bodnarchuk, Sheila Sanders, Sunil Deokule, Sachin Kedar — 2013-12-04

Objective: To determine if volunteers can simulate and reproduce 3 types of neurologic field defects: hemianopia, quadrantanopia, and central scotoma.Design: Cross-sectional study.Participants: Thirty healthy volunteers new to perimetry (including automated perimetry).Methods: After informed consent, volunteers were randomized to 1 of the 3 visual field defects listed above. All visual field testing was performed on the right eye using the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA) SITA Fast 24-2 protocol. Each volunteer was provided with standard new patient instructions and was shown a diagram of the defect to be simulated. Two sets of visual fields were performed on the right eye with 10 minutes between tests. Three experts used the Ocular Hypertension Treatment Study reading center criteria and determined if the simulation was successful.Main Outcome Measures: Proportion of volunteers able to simulate the assigned visual field.Results: All 10 volunteers (100%) successfully simulated a hemianopia on the first and second fields. All 10 volunteers (100%) simulated a quadrantanopia on the first field and 9 (90%) did so on the second field. Eight volunteers (80%) successfully simulated a central scotoma in the first field and all 10 (100%) did so on in the second field. Reliability criteria were excellent. Forty-seven fields (78%) had 0 fixation losses, 48 (80%) had 0 false-positive results, and 44 (73%) had 0 false-negative results.Conclusions: It is easy to simulate reproducible and reliable neurologic field defects on automated perimetry using HFA.

Effect of Centration and Circularity of Manual Capsulorrhexis on Cataract Surgery Refractive Outcomes

Mali Okada, Dov Hersh, Eldho Paul, David van der Straaten — 2013-12-16

Purpose: To determine if postoperative refractive outcome in cataract surgery relates to centration or circularity of the capsulorrhexis.Design: Prospective, observational study.Participants: One hundred thirteen eyes from 108 patients undergoing routine phacoemulsification cataract surgery with manual continuous curvilinear capsulorrhexis.Methods: Patients underwent refraction, and digital retroillumination photographs were obtained 1 month and 1 year after surgery. Capsulorrhexis parameters were analyzed using computer photographic software.Main Outcome Measures: Postoperative spherical equivalent (SE), deviation from predicted refraction, and postoperative spectacle cylinder.Results: At 1 month, mean capsulorrhexis circularity index was 0.83±0.01 mm and mean decentration was 0.30±0.14 mm. There was no significant correlation between either circularity or decentration and any of the refractive outcomes of SE, deviation from predicted refraction, or spectacle cylinder at 1 month or at 1 year. In contrast, an association between capsulorrhexis decentration and change in postoperative SE from 1 month to 1 year was observed: 56% of patients with more than 0.4 mm of decentration had a change in SE of more than 0.25 diopter (D) compared with 30% with 0.4 mm or less of decentration (P = 0.04). In eyes with incomplete capsulorrhexis–optic overlap, 60% had a change in spectacle cylinder of more than 0.50 D from 1 month to 1 year, compared with 15% of eyes with complete overlap (P = 0.004).Conclusions: Postoperative refraction at 1 year was not related to centration or circularity of the capsulorrhexis. However, decentration by more than 0.4 mm was associated with a 0.25-D change in SE and incomplete capsulorrhexis–optic overlap was associated with a 0.50-D change in spectacle cylinder from 1 month to 1 year.

Results of Toric Intraocular Lenses for Post-Penetrating Keratoplasty Astigmatism

Matthew Wade, Roger F. Steinert, Sumit Garg, Marjan Farid, Ronald Gaster — 2013-12-09

Purpose: Evaluate the usefulness of toric intraocular lens (IOL) implantation during cataract surgery in patients after penetrating keratoplasty (PKP).Design: Retrospective case review.Participants: A total of 21 eyes of 16 patients with prior PKP and moderate to high regular astigmatism after full suture removal underwent phacoemulsification and implantation of a single-piece acrylic toric IOL (SN6AT series; Alcon, Fort Worth, TX).Methods: Patients underwent comprehensive examinations at standard intervals, including visual acuity, manifest refraction, and corneal topography.Main Outcome Measures: Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) expressed as the logarithm of the minimum angle of resolution (logMAR) and manifest refraction astigmatism.Results: From preoperatively to the last visit (mean, 14.7 ± standard deviation 12.8 months), the 21 eyes had significant improvement in UDVA (logMAR, 0.90±0.48 to 0.23±0.25; P = 0.0001) and CDVA (logMAR, 0.31±0.14 to 0.08±0.13; P = 0.0001). A total of 14 of 21 eyes (67%) and 17 of 21 eyes (81%) had UDVA and CDVA of ≥20/30, respectively. Preoperative topographic astigmatism was 4.57±2.05 diopters (D). Postoperative manifest refraction astigmatism was 1.58±1.25 D overall, but lower (0.75±0.54 D) in the T7–T9 subgroup (excluding 1 outlier whose corneal astigmatism doubled after surgery) than in the T4–T6 subgroup (1.88±1.28 D; P = 0.013). A total of 16 of all 21 eyes (76.2%) and 8 of 9 eyes (89%) in the T7–T9 subgroup were within 1 D of postoperative manifest astigmatism as predicted or better.Conclusions: Toric IOLs placed during cataract surgery after PKP and full suture removal can reduce manifest refraction cylinder to predictably low levels with corresponding improvement in UDVA and CDVA in patients with moderate to high regular preoperative topographic astigmatism.

Factors Predictive of Remission of New-Onset Anterior Uveitis

2013-12-16

Purpose: To identify factors predictive of remission of inflammation in new-onset anterior uveitis cases treated at tertiary uveitis care facilities.Design: Retrospective cohort study.Participants: Patients seeking treatment at participating academic uveitis clinics within 90 days of initial diagnosis of anterior uveitis.Methods: Retrospective cohort study based on standardized chart review.Main Outcome Measures: Factors predictive of remission (no disease activity without corticosteroid or immunosuppressive treatments at all visits during a 90-day period).Results: Nine hundred ninety eyes (687 patients) had a first-ever diagnosis of anterior uveitis within 90 days before initial presentation and had follow-up visits thereafter. The median follow-up time was 160 days. Systemic diagnoses with juvenile idiopathic arthritis (JIA; adjusted hazard ratio [aHR], 0.38; 95% confidence interval [CI], 0.19–0.74) and Behçet's disease (aHR, 0.10; 95% CI, 0.01–0.85) were associated with a lower incidence of uveitis remission. Cases of bilateral uveitis (aHR, 0.68; 95% CI, 0.54–0.87) and those with a history of cataract surgery before presentation (aHR, 0.51; 95% CI, 0.29–0.87) also had a lower incidence of remission. Regarding clinical findings at the initial visit, a high degree of vitreous cells at initial presentation was associated with a lower incidence of remission (for 1+ or more vs. none: aHR, 0.72; 95% CI, 0.55–0.95). An initial visual acuity of 20/200 or worse, with respect to 20/40 or better, also was predictive of a lower incidence of remission (aHR, 0.52; 95% CI, 0.32–0.86).Conclusions: Factors associated with a lower incidence of remission among new-onset anterior uveitis cases included diagnosis with JIA, Behçet's disease, bilateral uveitis, history of cataract surgery, findings of 1+ or more vitreous cells at presentation, and an initial visual acuity of 20/200 or worse. Patients with these risk factors seem to be at higher risk of persistent inflammation; reciprocally, patients lacking these factors would be more likely to experience remission. Patients with risk factors for nonremission of uveitis should be managed taking into account the higher probability of a chronic inflammatory course.

Expert Panel Recommendations for the Use of Anti–Tumor Necrosis Factor Biologic Agents in Patients with Ocular Inflammatory Disorders

2013-12-18

Topic: To provide recommendations for the use of anti-tumor necrosis factor α (TNF-α) biologic agents in patients with ocular inflammatory disorders.Clinical Relevance: Ocular inflammatory diseases remain a leading cause of vision loss worldwide. Anti–TNF-α agents are used widely in treatment of rheumatologic diseases. A committee of the American Uveitis Society performed a systematic review of literature to generate guidelines for use of these agents in ocular inflammatory conditions.Methods: A systematic review of published studies was performed. Recommendations were generated using the Grading of Recommendations Assessment, Development, and Evaluation group criteria.Results: Numerous studies including controlled clinical trials have demonstrated that anti–TNF-α biologic agents (in particular infliximab and adalimumab) are effective in the treatment of severe ocular inflammatory disease. Based on these studies, the expert panel makes the following recommendations.Conclusions: Infliximab and adalimumab can be considered as first-line immunomodulatory agents for the treatment of ocular manifestations of Behçet's disease. Infliximab and adalimumab can be considered as second-line immunomodulatory agents for the treatment of uveitis associated with juvenile arthritis. Infliximab and adalimumab can be considered as potential second-line immunomodulatory agents for the treatment of severe ocular inflammatory conditions including posterior uveitis, panuveitis, severe uveitis associated with seronegative spondyloarthropathy, and scleritis in patients requiring immunomodulation in patients who have failed or who are not candidates for antimetabolite or calcineurin inhibitor immunomodulation. Infliximab and adalimumab can be considered in these patients in preference to etanercept, which seems to be associated with lower rates of treatment success.

Resident and Fellow Participation in Strabismus Surgery: Effect of Level of Training and Number of Assistants on Operative Time and Cost

2013-11-21

Objective: To investigate the effect of the level of training and number of assistants on operative time for uncomplicated, 2-muscle, horizontal strabismus surgery at an academic institution.Design: Comparative case series.Participants: A total of 993 children and adults between the ages of 6 months and 75 years.Methods: Retrospective chart review of strabismus surgeries performed between July 1, 2008, and December 31, 2012, by any of 3 attending surgeons assisted by a resident in the postgraduate year 3 (PGY3), fellow in the postgraduate year 5 (PGY5), or both.Main Outcome Measures: Operative time (minutes) and associated operative cost (dollars).Results: There were 373 cases with 1 assistant and 44 cases with 2 assistants. Of all cases with 1 assistant, there were 200 cases with a PGY3 assistant an average operative time of 62.5 minutes (standard deviation [SD], 15.1) and 173 cases with a PGY5 assistant an average operative time of 59.0 minutes (SD, 14.7); the difference of 3.5 minutes was statistically significant (P = 0.02). The average operative time for all cases with 2 assistants (both PGY3 and PGY5) was 10.6 minutes longer than all cases with 1 assistant (P = 0.0002). No statistically significant variation in operative times was demonstrated when comparing cases with a PGY3 (P = 0.29) and PGY5 (P = 0.44) assistant in their respective first and last halves of the academic year, but operative times within individual quarters of the academic year were significant for PGY3 (P = 0.03) but not for PGY5 (P = 0.24) assistant cases. Operative times were significantly different for individual PGY3 (P = 0.03) but not PGY5 (P = 0.22) assistant cases. Cost per PGY3 assistant per year for additional operative time is $3141.95.Conclusions: Operative time in strabismus surgery increased with PGY3 participation and further increased with both assistants over either assistant alone. Operative times earlier in the year did not vary from those later in the year for PGY3 or PGY5 assistants. The difference in quarterly and individual PGY3 but not PGY5 assistant operative times suggests that efficiency in strabismus surgery varies by assistants with less experience or interest.

Acetazolamide in Retinoschisis: A Prospective Study

2013-12-03

X-linked retinoschisis (XLRS) is the leading cause of hereditary juvenile macular degeneration in males with an estimated prevalence ranging from 1 in 15 000 to 1 in 30 000. It accounts for approximately 5% of all childhood-onset inherited retinal dystrophies. It is caused by mutations in the RS1 gene encoding retinoschisin resulting in schitic changes traversing the retinal layers. Clinical findings include bilateral, cystlike macular changes, and areas of peripheral bullous elevation. Vision is affected progressively with age, leading to poor central vision after the fifth decade of life. Currently, there is no medical treatment available for XLRS.

Abnormal Deep Retinal Capillary Networking and Microaneurysms in the Outer Nuclear Layer of Diabetic Eyes

Giuseppe Querques, Francesco Bandello, Eric H. Souied — 2013-12-02

Diabetic retinopathy (DR) is the leading cause of legal blindness in several countries. In DR, breakdown of the inner blood–retinal barrier, with leakage of plasma from small blood vessels, is responsible for the swelling of central retina and development of diabetic macular edema (DME). However, different pathophysiologic mechanisms may be involved in the development of DME, and they are believed to be associated with the various therapeutic responses and prognosis.

The Effect of Colored Overlays on Reading Performance in Infantile Nystagmus

Niraj Barot, Rebecca J. McLean, Irene Gottlob, Frank A. Proudlock — 2013-12-04

Infantile nystagmus (IN) is an involuntary oscillations of the eyes with onset within 6 months from birth. It can result in vision loss owing to constant retinal motion and lead to significant psychosocial problems. Recent studies have described reading deficits associated with IN and found that they can be relatively mild under optimal reading conditions, but are more apparent when reading smaller font sizes. Colored overlays have been tested in numerous diseases for improving reading performance but not in IN. Newman Wright et al have found them to be beneficial in multiple sclerosis, a condition associated with acquired pendular nystagmus and other visual symptoms such as optic neuritis.

Corrigendum

2014-03-01

The authors of “Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment: Three Year Randomized Trial Results” (Ophthalmology 2012;119:2312–2318) would like to clarify the following statement, which applies throughout the manuscript:

Quantitative Measurement of Interocular Suppression in Anisometropic Amblyopia

Carrie Huisingh, Gerald McGwin — 2014-01-24

We read with great interest the recently published study by Li et al and would like to provide feedback on a several issues related to their methodology, statistical analysis, and sample selection. This study is described as both a case-control study and a cohort study; however, the former description is incorrect. A case-control study would involve a group of patients who have the outcome of interest (cases) and a group of patients who do not have the outcome of interest (controls). In the current study, the authors selected a group of participants based on an exposure of interest, anisometropic amblyopia. Although anisometropic amblyopia is a disease, the authors' underlying hypothesis is that amblyopia affects visual function, and in this context of their study, amblyopia is considered a risk factor. Those with anisometropic amblyopia were given occlusion therapy and followed over time; clinical and suppression measurements were collected before and after therapy. As such, although this design clearly reflects a cohort study design, the description of any aspect of this design as a case-control study is erroneous.

Author reply

Jinrong Li, Minbin Yu, Robert F. Hess, Lily Y. Chan, Benjamin S. Thompson — 2014-01-24

First, We really appreciate Huisingh and McGwin's interest in our recent publication regarding the study of suppression in patients with anisometropic amblyopia. However, the concerns they raise in their recent correspondence are not directly relevant to our study. The aim of our study was not to measure suppression before and after occlusion therapy. Rather, measurements of suppression, stereopsis, and visual acuity were made in observers with amblyopia (cases) and age-matched observers without amblyopia (controls). For a number of measurements, visual acuity was decreased in the nondominant eye of each control using optical defocus so that it matched the amblyopic eye visual acuity of the case with whom they were paired. In addition, suppression was simulated in controls using neutral density filters. We also examined the relationships between acuity, stereopsis, and suppression in observers with amblyopia and explored the acute effects of spectacle and rigid gas-permeable contact lens correction on suppression in a specified subset of 19 cases (Figure 4 in our original paper). Once the case-control phase of the study was complete, 26 cases had subsequently received occlusion therapy combined with spectacle correction as part of their standard clinical care. Measurements of amblyopic eye visual acuity made at the first follow-up visit after treatment initiation were available for these cases. It has previously been reported that pretreatment measurements of suppression may be related to the outcomes of occlusion therapy, whereby stronger pretherapy suppression is associated with a poorer response to therapy. We therefore investigated whether a similar effect was present in the subset of our cases who had received treatment. We found that cases whose treatment had resulted in an amblyopic eye visual acuity improvement of <0.2 logarithm of the minimum angle of resolution had significantly stronger pretreatment suppression than those whose treatment was considered successful (>0.2 logarithm of the minimum angle of resolution acuity improvement). Detailed descriptions of the experimental design and analyses outlined are provided in our original manuscript.

CABP4 Mutations Do Not Cause Congenital Stationary Night Blindness

Arif O. Khan — 2013-12-13

I read with interest the analysis of Dutch patients diagnosed with congenital stationary night blindness (CSNB) by Bijveld et al, particularly what was written regarding patients with recessive mutations in calcium binding protein 4 (CABP4; Mendelian Inheritance in Man *608965). CABP4 encodes a protein that is specifically located in photoreceptor synaptic terminals, where it probably modulates photoreceptor calcium release. Only 3 of 101 patients diagnosed with CSNB in the authors' series had CABP4 mutations, and all 3 patients (2 families) harbored the same homozygous mutation (c.646C>T; p.Arg216X). These 3 patients had nystagmus and low vision. Two were photophobic. All 3 had a normal fundus appearance and severe color deficiency. None complained of night blindness. All 3 were hyperopic. Such signs and symptoms, combined with their cone–rod dysfunction by electroretinography, should suggest a diagnosis of cone-rod disease rather than predominantly rod disease such as CSNB. However, because during scotopic flash stimulus there was an electronegative waveform, which is classically associated with CSNB, the 3 patients were labeled as CSNB2 (“incomplete CSNB,” with the “incomplete” referring to some rod function being present rather than completely absent). The authors recognized that these 3 patients had a distinct phenotype that was atypical for a diagnosis of CSNB2 and wondered whether studies of additional patients would confirm or refute their findings.

Anterior Cerebral Circulation Infarction and Retinal Ganglion Cell Degeneration

Mitchell Lawlor, Gordon Plant — 2013-12-23

We congratulate Park et al on replicating our group's work demonstrating that transsynaptic retrograde degeneration (TRD) of retinal ganglion cells occurs after occipital injury. Their paper is interesting in that it seems to show this process occurring not only after occipital injury, but also after infarction of other areas of the brain. It would be of major theoretical importance if retinal nerve fiber layer (RNFL) thinning could be seen after damage to anterior brain areas with no damage to the pre- or postgeniculate visual pathway.

Author reply

Hae-Young L. Park, Chan Kee Park — 2013-12-23

We are pleased to receive comments regarding our manuscript reporting transsynaptic retrograde degeneration (TRD) of retinal ganglion cells after infarction in various areas of the brain. We measured retinal nerve fiber layer (RNFL) thickness to indirectly observe TRD of retinal ganglion cells. Previous work by Jindahra et al showed TRD of retinal ganglion cells after congenital or acquired occipital lobe injury. Our work differed from their study because our patients had acquired brain lesions owing to ischemic stroke. They had various stroke lesions, including lesions other than in the occipital lobe.

Ethnic Difference in Myopia between Asians and Non-Hispanic Whites in the United States

Chen-Wei Pan — 2013-12-16

The excellent article by Wen et al supports what has been noted by ophthalmic epidemiologists, namely that myopia seems to much more prevalent in preschool children of Asian descendants (mainly Chinese) than non-Hispanic whites in the United States, with a 3-fold difference in prevalence (3.98% vs 1.20%). I feel this finding deserves further discussion. In the Multi-Ethnic Study of Atherosclerosis on middle-aged to elderly adults in the United States, the magnitude of difference in myopia prevalence between the 2 ethnic groups was much smaller (37.2% in Chinese and 31.0% in non-Hispanic whites).

Ophthalmology

Editorial Board

This Issue At A Glance

A Simple Vista en Este Número

期刊一览

Contents

NEI's Audacious Goals Initiative

A Close Look at Pediatric Eye Disease

Ophthalmic Patient Data Registries: Defining and Improving Quality and Outcomes

Risk Factors for Amblyopia in the Vision in Preschoolers Study

Prevalence of Vision Disorders by Racial and Ethnic Group among Children Participating in Head Start

Mortality in Patients with Central Retinal Vein Occlusion

United Kingdom National Ophthalmology Database Study of Vitreoretinal Surgery: Report 3, Retinal Detachment

Vitrectomy with Internal Limiting Membrane Peeling versus No Peeling for Idiopathic Full-Thickness Macular Hole

Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials

Genetic Susceptibility, Dietary Antioxidants, and Long-Term Incidence of Age-Related Macular Degeneration in Two Populations

Comparison of Outcomes from a Phase 3 Study of Age-Related Macular Degeneration with a Matched, Observational Cohort

RADIANCE: A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization Secondary to Pathologic Myopia

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration: The COMPLETE Study

Histopathology of Streptococcus Mitis/Oralis Endophthalmitis after Intravitreal Injection with Bevacizumab: A Report of 7 Patients

The Spectrum of Ocular Alterations in Patients with β-Thalassemia Syndromes Suggests a Pathology Similar to Pseudoxanthoma Elasticum

En Face Enhanced-Depth Swept-Source Optical Coherence Tomography Features of Chronic Central Serous Chorioretinopathy

Driving Habits in Older Patients with Central Vision Loss

Association between Visual Field Defects and Quality of Life in the United States

Defining 10-2 Visual Field Progression Criteria: Exploratory and Confirmatory Factor Analysis Using Pointwise Linear Regression

Retinal Blood Flow in Glaucomatous Eyes with Single-Hemifield Damage

The Ability of Healthy Volunteers to Simulate a Neurologic Field Defect on Automated Perimetry

Effect of Centration and Circularity of Manual Capsulorrhexis on Cataract Surgery Refractive Outcomes

Results of Toric Intraocular Lenses for Post-Penetrating Keratoplasty Astigmatism

Factors Predictive of Remission of New-Onset Anterior Uveitis

Expert Panel Recommendations for the Use of Anti–Tumor Necrosis Factor Biologic Agents in Patients with Ocular Inflammatory Disorders

Resident and Fellow Participation in Strabismus Surgery: Effect of Level of Training and Number of Assistants on Operative Time and Cost

Acetazolamide in Retinoschisis: A Prospective Study

Abnormal Deep Retinal Capillary Networking and Microaneurysms in the Outer Nuclear Layer of Diabetic Eyes

The Effect of Colored Overlays on Reading Performance in Infantile Nystagmus

Corrigendum

Quantitative Measurement of Interocular Suppression in Anisometropic Amblyopia

Author reply

CABP4 Mutations Do Not Cause Congenital Stationary Night Blindness

Anterior Cerebral Circulation Infarction and Retinal Ganglion Cell Degeneration

Author reply

Ethnic Difference in Myopia between Asians and Non-Hispanic Whites in the United States