Objective  To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, but dilated eye evaluations may be a more cost-effective policy.

Design  Monte Carlo cost-effectiveness simulation model with a total of 50 000 simulated patients with demographic characteristics matched to persons 65 years of age in the US population.

Results  Compared with no screening policy, dilated eye evaluations increased quality-adjusted life-years (QALYs) by 0.008 (95% credible interval [CrI], 0.005-0.011) and increased costs by $94 (95% CrI, –$35 to $222). A visual acuity screening increased QALYs in less than 95% of the simulations (0.001 [95% CrI, –0.002 to 0.004) and increased total costs by $32 (95% CrI, –$97 to $159) per person. The incremental cost-effectiveness ratio of a visual acuity screening and an eye examination compared with no screening were $29 000 and $12 000 per QALY gained, respectively. At a willingness-to-pay value of $15 000 or more per QALY gained, a dilated eye evaluation was the policy option most likely to be cost-effective.

Conclusions  The currently recommended visual acuity screening showed limited efficacy and cost-effectiveness compared with no screening. In contrast, a new policy of reimbursement for Welcome to Medicare dilated eye evaluations was highly cost-effective.

Objectives  To assess the impact of thrombospondin 1 (TSP1) deficiency on choroidal neovascularization (CNV) and to determine whether administration of a TSP1 antiangiogenic mimetic peptide attenuates CNV.

Methods  The impact of TSP1 deficiency on laser-induced CNV was assessed using wild-type (TSP1+/+) and TSP1-deficient (TSP1–/–) mice. Three laser burns were placed in each eye of TSP1+/+ and TSP1–/– mice to induce CNV. Intravitreal injection of the TSP1 mimetic peptide was performed on days 1 and 7 postlaser in the mice. For quantitative measurements of neovascularization, intercellular adhesion molecule 2 staining was performed at 14 days postlaser of the choroidal-sclera flat mounts. The recruitment of macrophages to the sites of damage was investigated by immunohistochemistry. The CNV area was measured by intercellular adhesion molecule 2 staining and use of ImageJ software.

Results  The TSP1–/– mice exhibited significantly larger areas of neovascularization on choroidal flat mounts compared with TSP1+/+ mice. This was consistent with enhanced recruitment of macrophages in TSP1–/– mice compared with TSP1+/+ mice 3 days postlaser. The development of CNV was significantly attenuated in mice receiving the TSP1 antiangiogenic mimetic peptide compared with those receiving vehicle alone.

Conclusions  Deficiency of TSP1 contributes to enhanced choroidal neovascularization. This is consistent with the anti-inflammatory and antiangiogenic activity of TSP1. The TSP1 antiangiogenic peptide was effective in attenuation of CNV.

Clinical Relevance  Intravitreal injection of TSP1 antiangiogenic mimetic peptides may provide alternative treatment for CNV.

Objective  To investigate whether the severity of cystoid macular edema (CME) in neonates who were 31 to 36 weeks' postmenstrual age, as viewed by spectral-domain optical coherence tomography (SD-OCT) imaging, predicts the severity of retinopathy of prematurity (ROP) or is related to systemic health.

Design  Of 62 prematurely born neonates in a prospective institutional review board–approved study, 42 met the following inclusion criteria: at least 1 SD-OCT imaging session prior to 37 weeks' postmenstrual age and prior to ROP laser treatment, if a laser treatment was performed, and an ophthalmic ROP examination at or after 41 weeks' postmenstrual age, evidence of complete retinal vascularization in zone III, or documentation through telephone report of such information after transfer of care. Measures of CME severity, including central foveal thickness, retinal layer thicknesses, and foveal-to-parafoveal thickness ratio in 1 eye per subject, were compared with ROP outcomes: laser treatment, maximum plus disease, and maximum ROP stage. Systemic health factors were also correlated.

Results  Cystoid macular edema was present in 50% of neonates. Multiple elongated cystoid structures within the inner nuclear layer were most common. The presence of CME was not associated with ROP outcomes. The central foveal thickness, the thickness of the inner retinal layers, and the foveal-to-parafoveal thickness ratio were higher in eyes that required laser treatment or that developed plus disease or ROP stage 3. Cystoid macular edema was not clearly associated with systemic factors.

Conclusions  Cystoid macular edema is common in premature infants screened for ROP before 37 weeks' postmenstrual age, with the most common SD-OCT phenotype of a bulging fovea from multiple elongated cystoid spaces. Detection of CME is not associated with ROP severity; however, tomographic thickness measurements could potentially predict a higher risk of requiring laser treatment or developing plus disease or ROP stage 3. Systemic health factors are probably not related to the development of CME.

Objectives  To assess focal lamina cribrosa (LC) defects in glaucoma using enhanced depth imaging optical coherence tomography and to investigate their spatial relationships with neuroretinal rim and visual field loss.

Methods  Serial horizontal and vertical enhanced depth imaging optical coherence tomographic images of the optic nerve head were obtained from healthy subjects and those with glaucoma. Focal LC defects defined as anterior laminar surface irregularity (diameter, >100 µm; depth, >30 µm) that violates the normal smooth curvilinear contour were investigated regarding their configurations and locations. Spatial consistency was evaluated among focal LC defects, neuroretinal rim thinning/notching, and visual field defects.

Results  Forty-six healthy subjects (92 eyes) and 31 subjects with glaucoma (45 eyes) were included. Ninety-eight focal LC defects representing various patterns and severity of laminar tissue loss were found in 34 eyes with glaucoma vs none in the healthy eyes. Seven of 11 eyes with glaucoma with no visible focal LC defect had a deeply excavated optic disc with poor LC visibility. Eleven focal LC defects presented clinically as an acquired pit of the optic nerve, and the others as neuroretinal rim thinning/notching. Focal LC defects preferably occurred in the inferior/inferotemporal far periphery of the LC including its insertion. Eyes with focal LC defects limited to the inferior half of the optic disc had greater sensitivity loss in the superior visual hemifield and vice versa.

Conclusions  Mechanisms of LC deformation in glaucoma include focal loss of laminar beams, which may cause an acquired pit of the optic nerve in extreme cases. Focal LC defects occur in tandem with neuroretinal rim and visual field loss.

Objectives  To determine the efficacy of refractive correction alone and patching treatment with near activities on amblyopia associated with myopic anisometropia in children aged 4 to less than 14 years. The associations of visual acuity (VA) improvement with age, degree of anisometropia, patching compliance, presence of strabismus, and presence of eccentric fixation were also investigated.

Methods  Seventeen amblyopic children were recruited (range of VA in the amblyopic eye, 20/80 to 20/400). Visual acuity was assessed at 4, 8, 12, and 16 weeks while participants wore spectacles and/or contact lenses for full refractive correction. Patching treatment was initiated at the 16-week visit. The primary outcome was VA after 16 weeks of refractive correction alone and final VA after 16 weeks of patching.

Results  The mean (SD) baseline VA in the amblyopic eye was 0.96 (0.27) logMAR, which improved to a mean (SD) of 0.84 (0.24) logMAR with refractive correction and to a mean (SD) of 0.71 (0.30) logMAR after the addition of patching (P < .001). Comparing the final VA with the baseline VA, we found that VA improvement averaged 2.59 lines. The final VA in the amblyopic eye was associated with the baseline VA in the amblyopic eye (P < .001), the magnitude of anisometropia (P < .001), and the level of patching compliance (P = .04). The improvement in VA with patching was inversely associated with participants' age (P = .03) and presence of eccentric fixation (P = .02).

Conclusion  Both refractive correction and patching significantly improved the VA of the amblyopic eye associated with myopic anisometropia, with 88% of participants' eyes improving 2 lines or more. Further improvement in VA was observed when patching plus near activities was added to refractive correction and patients were followed for 16 more weeks. We recommend that clinicians treat myopic anisometropic amblyopia with refractive correction and patching plus near activities.

Objectives  To compare different screening procedures for hydroxychloroquine sulfate (Plaquenil) toxicity at different stages of damage.

Methods  Ten patients were studied using 10-2 automated fields, multifocal electroretinography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence.

Results  All 10 patients used hydroxychloroquine for more than 6 years, and those with severe toxicity had been overdosed. Fundus examination findings were normal except for the patients with severe toxicity. All the patients showed parafoveal field loss, but this was sometimes subtle. Multifocal electroretinography demonstrated parafoveal weakness in the milder cases. The SD-OCT subfield thickness plots showed a ring of parafoveal thinning in all the patients. The SD-OCT cross-sections showed parafoveal loss of the inner segment–outer segment and cone outer segment tip lines at early stages of toxicity, progressing to parafoveal thinning of the outer nuclear layer and eventually to retinal pigment epithelium damage. There was a ring of autofluorescence in most patients.

Conclusions  Overdosage with hydroxychloroquine seemed a significant risk factor for toxicity. Different individuals were more or less sensitive to different tests. Fields can be sensitive but only if read with a low threshold for change. Hydroxychloroquine causes early parafoveal loss of the outer segment lines on SD-OCT, with the first changes often evident in the inferotemporal quadrant. Parafoveal thinning of the outer nuclear layer follows, before retinal pigment epithelium damage is visible. Careful screening with multiple tests can detect toxic damage before prominent loss of the outer nuclear layer.

Objective  To evaluate the cellular changes in the corneal epithelium and surrounding structures in limbal stem cell deficiency (LSCD) by using in vivo laser scanning confocal microscopy.

Methods  This was a prospective comparative study that included 27 eyes of 20 patients with LSCD and 12 eyes of 10 healthy subjects. All subjects underwent slitlamp examination, and LSCD was classified into 3 groups on the basis of clinical presentation. Confocal imaging of the central cornea and 4 locations of limbus was performed. Morphologic characteristics of the corneal epithelium were studied. The basal epithelial cell density and subbasal nerve density in the central cornea were calculated, and a potential correlation between the decrease in basal epithelial cell density and subbasal nerve density in LSCD was investigated.

Results  The wing and basal epithelial cells became progressively metaplastic, and the basal epithelial cell density and subbasal nerve density in the early and intermittent stages decreased significantly compared with controls (all P < .01). Normal basal epithelial cell morphology was completely lost and subbasal nerves were absent in the late stage of LSCD. The decrease in basal cell density correlated with the decrease in subbasal nerve density in patients with LSCD (P = .03).

Conclusions  There are significant microstructural changes associated with early LSCD. These cellular changes could help to understand the disease process and classify and monitor limbal stem cell dysfunction.

Objective  To compare visual acuity (VA) scores after autorefraction vs manual refraction in eyes of patients with diabetes mellitus and a wide range of VAs.

Methods  The letter score from the Electronic Visual Acuity (EVA) test from the electronic Early Treatment Diabetic Retinopathy Study was measured after autorefraction (AR-EVA score) and after manual refraction (MR-EVA score), which is the research protocol of the Diabetic Retinopathy Clinical Research Network. Testing order was randomized, study participants and VA examiners were masked to refraction source, and a second EVA test using an identical supplemental manual refraction (MR-EVAsuppl score) was performed to determine test-retest variability.

Results  In 878 eyes of 456 study participants, the median MR-EVA score was 74 (Snellen equivalent, approximately 20/32). The spherical equivalent was often similar for manual refraction and autorefraction (median difference, 0.00; 5th-95th percentile range, –1.75 to 1.13 diopters). However, on average, the MR-EVA scores were slightly better than the AR-EVA scores, across the entire VA range. Furthermore, the variability between the AR-EVA scores and the MR-EVA scores was substantially greater than the test-retest variability of the MR-EVA scores (P < .001). The variability of differences was highly dependent on the autorefractor model.

Conclusions  Across a wide range of VAs at multiple sites using a variety of autorefractors, VA measurements tend to be worse with autorefraction than manual refraction. Differences between individual autorefractor models were identified. However, even among autorefractor models that compare most favorably with manual refraction, VA variability between autorefraction and manual refraction is higher than the test-retest variability of manual refraction. The results suggest that, with current instruments, autorefraction is not an acceptable substitute for manual refraction for most clinical trials with primary outcomes dependent on best-corrected VA.

Objective  To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons.

Methods  In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed.

Results  Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (<–0.5 D) was significantly associated with a lower risk for AMD (odds ratio, 0.44; P < .001, compared with emmetropia) in Chinese men.

Conclusions  The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

Objective  To determine whether treatment with oral azithromycin compared with topical tetracycline reduces the recurrence of trichiasis for up to 3 years following surgery for trichiasis.

Methods  The Surgery for Trichiasis, Antibiotics to Prevent Recurrence (STAR) trial is a randomized, single-masked, clinical trial conducted in southern Ethiopia, a region where trachoma is hyperendemic. A total of 1452 patients who underwent trichiasis surgery were randomly assigned at a 2:1 ratio to either a single dose of oral azithromycin (1 g) or topical tetracycline (twice per day for 6 weeks) following surgery.

Main Outcome Measures  Recurrence of trichiasis within 3 years following surgery.

Results  The rate of recurrence was 10% in the azithromycin group and 13% in the tetracycline group. The azithromycin group had a 22% reduction in recurrence of trichiasis 3 years after surgery compared with the tetracycline group (P = .13). Severity of entropion at baseline was the most significant predictor of recurrence of trichiasis at 3 years.

Conclusion  Trichiasis recurrence rates in the STAR trial remained low for up to 3 years following surgery. The protective effect of a single dose of azithromycin was less than at 1 year and, although not statistically significant, was still suggestive up to 3 years following trichiasis surgery.

Application to Clinical Practice  A single dose of azithromycin after surgery remains an integral component of the World Health Organization's strategy for the elimination of trachoma by the year 2020.

Trial Registration  clinicaltrials.gov Identifier: NCT00347776.