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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Methods  In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis.

Results  The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 μm, and control patients had a mean photoreceptor equivalent thickness of 21.8 μm, a mean difference of 6.5 μm (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P = .53).

Conclusions  The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE.

Clinical Relevance  These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of therapeutic interventions.

Design  Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction.

Results  During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1% vs 7.1%; adjusted hazard ratio, 1.45; 95% confidence interval, 1.24-1.69; P < .001). There was no evidence of interaction by advanced carotid atherosclerosis (P > .10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging.

Conclusions  These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.

Methods  A total of 114 infants between 1 and 6 months of age with a unilateral congenital cataract were assigned to undergo cataract surgery either with or without an intraocular lens implant. Standardized definitions of glaucoma and glaucoma suspect were created and used in the IATS.

Results  Of these 114 patients, 10 (9%) developed glaucoma and 4 (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma-related adverse event in the treated eye through the first year of follow-up. Of the 57patients who underwent lensectomy and anterior vitrectomy, 5 (9%) developed a glaucoma-related adverse event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma-related adverse event. The odds of developing a glaucoma-related adverse event were 3.1 times higher for a child with persistent fetal vasculature and 1.6 times higher for each month of age younger at cataract surgery.

Conclusions  Modern surgical techniques do not eliminate the early development of glaucoma following congenital cataract surgery with or without an intraocular lens implant. Younger patients with or without persistent fetal vasculature seem more likely to develop a glaucoma-related adverse event in the first year of follow-up. Vigilance for the early development of glaucoma is needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a child with persistent fetal vasculature. Five-year follow-up data for the IATS will likely reveal more glaucoma-related adverse events.

Trial Registration  clinicaltrials.gov Identifier: NCT00212134

Methods  In 150 consecutive eyes that underwent Descemet membrane endothelial keratoplasty, the incidence and type of graft detachment were studied at 1, 3, 6, 9, 12, and 24 months after surgery in a nonrandomized, prospective clinical study at a tertiary referral center. Four groups of detachments were identified: a partial detachment of one-third or less of the graft surface area (n = 16; group 1); a partial detachment of more than one-third of the graft surface area (n = 8; group 2); a graft positioned upside down (n = 4; group 3); and a free-floating Descemet roll in the host anterior chamber (n = 8; group 4).

Results  Partial or complete graft detachment was found in 36 cases (24%), of which 18 (12%) were clinically significant. All 24 eyes with a partial detachment (groups 1 and 2) showed spontaneous corneal clearance, and all but 6 of these eyes (75%) reached visual acuity of 20/40 or better (≥0.5). A reversed clearance pattern and interface spikes were observed in eyes with the graft positioned upside down (group 3). Eyes with a free-floating graft (group 4) showed persistent corneal edema. Detachments were associated with inward folds (12 eyes [33%]), insufficient air-bubble support (7 eyes [19%]), upside-down graft positioning (4 eyes [11%]), use of plastic materials (2 eyes [6%]), irido-graft synechiae (1 eye [3%]), poor endothelial morphology (1 eye [3%]), and stromal irregularity under the main incision (1 eye [3%]); 14 (58%) of the partial detachments were localized inferiorly.

Conclusions  Awaiting spontaneous clearance may be advocated in eyes with a partial detachment. Minor adjustments in surgical protocol as well as careful patient selection may further reduce the incidence of graft detachment after Descemet membrane endothelial keratoplasty to 4% or less.

Trial Registration  clinicaltrials.gov Identifier: NCT00521898

Methods  We examined the temporospatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence) and 795 nm (near-infrared autofluorescence) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up, 11-57 months; mean, 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations.

Results  Longitudinal fundus autofluorescence imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were nonrandom and followed a radial path that left behind a trail of diminishing autofluorescence. Longitudinal near-infrared autofluorescence imaging also demonstrated centrifugal lesion spread but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. Fundus autofluorescence and near-infrared autofluorescence abnormalities were spatially correlated with each other, and together they reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease.

Conclusions  Stargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in retinal pigment epithelial cells. These progressive foveal-to-peripheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.

Methods  This was a cohort study nested within a randomized clinical trial. There were 235 participants with glaucoma who had a single previous trabeculectomy augmented with either intraoperative 5-fluorouracil or placebo. Cataract surgery with intraocular lens implantation was performed on participants judged to have significant lens opacity. Cox regression was performed to evaluate the effect of time between trabeculectomy and cataract surgery on the time to trabeculectomy failure, after adjusting for other relevant risk factors. The main outcome measure was time to failure of trabeculectomy, defined as an intraocular pressure of greater than 21 mm Hg.

Results  Of the 235 participants, 124 (52.7%) underwent subsequent cataract surgery. The median time from trabeculectomy to cataract surgery for these patients was 21.7 months (range, 4.6-81.9 months). The median follow-up period was 60 months (range, 28-84 months) for the cataract surgery group and 48 months (range, 12-84 months) for the non–cataract surgery group. Cox regression showed that the time from trabeculectomy to cataract surgery was significantly associated with time to trabeculectomy failure (hazard ratio, 1.73 [95% CI, 1.05-2.85]; P = .03). The adjusted declining hazard ratios for risk of subsequent trabeculectomy failure when cataract surgery was performed 6 months, 1 year, and 2 years after trabeculectomy were 3.00 (95% CI, 1.11-8.14), 1.73 (95% CI, 1.05-2.85), and 1.32 (95% CI, 1.02-1.69), respectively.

Conclusions  Cataract surgery after trabeculectomy increases the risk of trabeculectomy failure, and this risk is increased if the time between trabeculectomy and cataract surgery is shorter.

Methods  Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization.

Main Outcome Measures  The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation.

Results  Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (–0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, –0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, –0.31 to –0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (–0.37 to –0.04; P = .02).

Conclusions  We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers.

Application to Clinical Practice  Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers.

Trial Registration  clinicaltrials.gov Identifier: NCT00324168

Methods  Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbiological results, and patient demographics, for patients enrolled in the trial.

Results  Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P = .04) and deeper infiltrates (P = .04) and were more likely to be localized centrally (P = .002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n = 366, 72%).

Conclusions  The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation.

Trial Registration  clinicaltrials.gov Identifier: NCT00324168

Design  Open-label, dose-escalation phase I study of 15 patients (range, 11-30 years of age) evaluated after subretinal injection of the rAAV2- RPE65 vector into the worse-functioning eye. Five cohorts represented 4 dose levels and 2 different injection strategies.

Main Outcome Measures  Primary outcomes were systemic and ocular safety. Secondary outcomes assayed visual function with dark-adapted full-field sensitivity testing and visual acuity with Early Treatment Diabetic Retinopathy Study charts. Further assays included immune responses to the vector, static visual fields, pupillometry, mobility performance, and optical coherence tomography.

Results  No systemic toxicity was detected; ocular adverse events were related to surgery. Visual function improved in all patients to different degrees; improvements were localized to treated areas. Cone and rod sensitivities increased significantly in the study eyes but not in the control eyes. Minor acuity improvements were recorded in many study and control eyes. Major acuity improvements occurred in study eyes with the lowest entry acuities and parafoveal fixation loci treated with subretinal injections. Other patients with better foveal structure lost retinal thickness and acuity after subfoveal injections.

Conclusions  Gene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina. There is no benefit and some risk in treating the fovea. No evidence of age-dependent effects was found. Our results point to specific treatment strategies for subsequent phases.

Application to Clinical Practice  Gene therapy for inherited retinal disease has the potential to become a future part of clinical practice.

Trial Registration  clinicaltrials.gov Identifier: NCT00481546

Methods  The Florida Agency for Health Care Administration ED data sets for ED outpatient visits and ED admissions for eye care were analyzed for type of insurance coverage and stratified according to age younger than 18 years and 18 years or older. Negative binomial regression models were used to measure the percentage of change in payer distribution for each 1-year increase in calendar year.

Results  During the 5-year study period, commercial insurance was the most frequent payer of ED outpatient services (31.1%), followed by self-pay (26.2%) and Medicaid (22.0%). For persons younger than 18 years, Medicaid and self-payment made up 67.7% of principal payers. For outpatient ED visits, the percentage of change in Medicaid increased 5.9% for each calendar year (P < .001) and commercial coverage declined 4.5% (P < .001 ). The proportion of Florida residents receiving Medicaid during the study period was less than the national average.

Conclusions  A substantial proportion of ED eye care in Florida is reimbursed through Medicaid or is paid for out of pocket. How the Patient Protection and Affordable Care Act of 2010 and the national economic recovery will affect safety-net institutions such as EDs and hospital staff is speculative, but the effect could be substantial.

Methods  In a retrospective study design, we created a histologic grading system based on common characteristics observed histologically among 92 DSAEK specimens sent to the University of Wisconsin Eye Pathology Laboratory with a clinical diagnosis of Fuchs dystrophy from 3 separate corneal surgeons. Cases were graded as mild, moderate, or severe on the basis of guttae dispersion, presence of a laminated Descemet membrane, presence of embedded guttae, and density of guttae. Regression models were built to study the relationship among preoperative VA, histologic findings, and best-corrected VA 6 months and 1 and 2 years after DSAEK.

Results  No correlation was found between the severity of histologic changes of Descemet membrane and preoperative VA. However, a correlation was noted between the preoperative and final VA. Cases with a laminated Descemet membrane but no embedded guttae (n = 8) appeared to be less responsive to DSAEK. Otherwise, the severity of histologic changes of Descemet membrane observed in patients with Fuchs corneal dystrophy after DSAEK did not show a statistically significant correlation with final VA.

Conclusions  Our analysis fails to show an inverse relationship between the severity of histologic changes of the Descemet membrane and the best-corrected VA of at least 20/40 after DSAEK for Fuchs endothelial dystrophy. However, in a subset of patients with Fuchs dystrophy who develop a laminated Descemet membrane without embedded guttae, the visual recovery after DSAEK is less than expected. The laminated architecture of Descemet membrane without embedded guttae may facilitate separation between the membrane layers and, thus, incomplete removal of the recipient's Descemet membrane during DSAEK, which may then limit the postoperative visual outcome.

Methods  A total of 32 eyes of 30 patients with pterygia were managed at the Ocular Surface Center from January 1, 2002, through December 31, 2010. The eyes were consecutively operated on by recession; sealing of the gap; covering of exposed medial rectus muscle by amniotic membrane, conjunctival autograft, or oral mucosal graft (OMG); and covering of the bare sclera with amniotic membrane. Main outcome measures were recurrence, diplopia, and caruncle morphological characteristics.

Results  Caruncle grading strongly correlated with residual conjunctiva (P = .01), severity of diplopia (P = .001), and overall success rate (P = .05). Amniotic membrane transplantation alone was successful in 23 eyes with residual conjunctiva of 27.8 (10.1) mm, which was significantly longer than those in 6 cases in which amniotic membrane transplantation failed (13.1 [11.4] mm, P = .007) and those in 8 cases in which amniotic membrane transplantation was successful but that required an additional conjunctival autograft or oral mucosal graft (10.9 [10.4] mm, P = .001). During mean (SD) follow-up of 27.5 (20.5) months, 30 of 32 eyes (94%) achieved total success without recurrence and diplopia and normal caruncle in 17 of 21 eyes (81%) with abnormal caruncle before surgery. One eye (3%) developed corneal recurrence and was lost to follow-up, and 1 eye (3%) was left with a depressed caruncle and residual diplopia on adduction.

Conclusions  Caruncle morphological characteristics and residual conjunctiva measurement help grade the severity of recurrent pterygium, guide surgical techniques, and predict outcomes. Sealing of the gap is important to create a strong barrier for preventing recurrence, restoring caruncle morphological characteristics, and regaining full motility in multirecurrent pterygia.

Methods  Retrospective review of 4 patients with a diagnosis of unilateral acute idiopathic maculopathy. Clinical characteristics (age, symptoms, Snellen visual acuity, and funduscopic features) and images from spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were analyzed.

Results  The median (range) age at presentation was 31 (27-52) years. The median (range) interval between symptom onset and presentation was 4 (1-20) weeks. Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive coxsackievirus titers (50%). The median (range) visual acuity at initial examination was 20/400 (20/70 to 1/400), which improved to 20/30 (20/20 to 20/60) at final follow-up. The median (range) follow-up time was 8 (8-13) weeks. Early in the disease course, the central macula developed irregular, circular areas of white-gray discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. Fluorescein angiography demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. Spectral-domain optical coherence tomography showed a partially reversible disruption of the outer photoreceptor layer. Fundus autofluorescence initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. Indocyanine green angiography showed "moth-eaten"–appearing choroidal vasculature, suggestive of choroidal inflammation.

Conclusions  The imaging characteristics highlight the structural changes during the active and resolution phases of unilateral acute idiopathic maculopathy. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible.

Methods  A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry. Eight eye cancer centers in 6 countries performed retrospective chart reviews. Statistical analysis included patient and tumor characteristics, ocular and angle abnormalities, management, histopathology, and outcomes.

Results  A total of 131 patients with iris melanoma (mean age, 64 years [range, 20-100 years]) were found to have blue-gray (62.2%), green-hazel (29.1%), or brown (8.7%) irides. Iris melanoma color was brown (65.6%), amelanotic (9.9%), and multicolored (6.9%). A mean of 2.5 clock hours of iris was visibly involved with melanoma, typically centered at the 6-o’clock meridian. Presentations included iritis, glaucoma, hyphema, and sector cataract. High-frequency ultrasonography revealed a largest mean tumor diameter of 4.9 mm, a mean maximum tumor thickness of 1.9 mm, angle blunting (52%), iris root disinsertion (9%), and posterior iris pigment epithelium displacement (9%). Using the American Joint Commission on Cancer–International Union Against Cancer classification, we identified 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3, and 1% of tumors as T4. Histopathologic grades were G1-spindle (54%), G2-mixed (28%), G3-epithelioid (5%), and undetermined (13%) cell types. Primary treatment involved radiation (26%) and surgery (64%). Kaplan-Meier analysis found a 10.7% risk of metastatic melanoma at 5 years.

Conclusions  Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris.

Methods  Subretinal injections (100 µL) of balanced salt solution were placed in the superotemporal macula of 1 eye in 3 cynomolgus macaques. Fellow eyes received intravitreal injections (100 µL) of balanced salt solution. Fundus photography, ocular coherence tomography, and multifocal electroretinography were performed before and immediately after injection and again at intervals up to 3 months postinjection. Histopathologic analyses included transmission electron microscopy and immunohistochemistry for glial fibrillary acidic protein, rhodopsin, M/L-cone opsin, and S-cone opsin.

Results  Retinas were reattached by 2 days postinjection (seen by ocular coherence tomography). Multifocal electroretinography waveforms were suppressed post–subretinal injection within the subretinal injection bleb and, surprisingly, also in regions far peripheral to this area. Multifocal electroretinography amplitudes were nearly completely recovered by 90 days. The spectral-domain ocular coherence tomography inner segment–outer segment line had decreased reflectivity at 92 days. Glial fibrillary acidic protein and S-cone opsin staining were unaffected. Rhodopsin and M/L-cone opsins were partially displaced into the inner segments. Transmission electron microscopy revealed disorganization of the outer segment rod (but not cone) discs. At all postinjection intervals, eyes with intravitreal injection were similar to baseline.

Conclusions  Subretinal injection is a promising route for drug delivery to the eye. Three months post–subretinal injection, retinal function was nearly recovered, although reorganization of the outer segment rod disc remained disrupted. Understanding the functional and anatomic effects of subretinal injection is important for interpretation of the effects of compounds delivered to the subretinal space.

Clinical Relevance  Subretinal injection is a new potential route for drug delivery to the eye. Separating drug effects from the procedural effects is critical.

Methods  An 8-mm stromal dissection was performed in the right eyes of adult New Zealand rabbits. Treatment with PEDF+DHA was for 6 weeks. Corneal sensation was measured weekly by Cochet-Bonnet esthesiometer. After 8 weeks, immunofluorescence with βIII-tubulin, calcitonin gene-related peptide, and substance P antibodies was performed to quantify nerves. Also, rabbits were treated with PEDF+DHA for 4 weeks after lamellar keratectomy, followed by 8-mm epithelial debridement and epithelial defect assessment. One week after surgery, corneas were stained with anti-Ki67 antibody to assess cell proliferation.

Results  Eight weeks after surgery, calcitonin gene-related peptide–positive nerve fibers in the PEDF+DHA group were similar to normal rabbit corneas but were decreased in the vehicle. Substance P was localized in the subepithelial plexus but appeared in epithelial cells after nerve injury regardless of treatment. Five weeks after surgery, an increase in corneal sensitivity occurred in the PEDF+DHA group and reached normal values by 8 weeks. Pigment epithelial–derived factor plus DHA increased epithelial wound healing after lamellar keratectomy. One week after epithelial injury, Ki67-positive cells increased in the limbal area.

Conclusion  Pigment epithelial–derived factor plus DHA promotes regeneration of calcitonin gene-related peptide–positive corneal nerves, accelerating wound healing and return of corneal sensitivity.

Clinical Relevance  Pigment epithelial–derived factor plus DHA represents a new approach to regenerate nerves and a potential treatment for prevention of severe dry eye after surgery or diseases of the ocular surface.

Methods  The effects of intraperitoneal injections of 400 μg of anti–VEGF-C antibody (treated group) and intraperitoneal normal saline (untreated group) were studied in murine dry eyes induced by exposing mice to high-flow desiccated air in a controlled-environment chamber. Growth of lymphatic vessels and infiltration of macrophages were evaluated by immunohistochemistry using CD31 (panendothelial marker), lymphatic vessel endothelial receptor 1 (lymphatic endothelial marker), and CD11b (monocyte and macrophage marker). Real-time polymerase chain reaction was performed to quantify expression of different inflammatory cytokine transcripts in the conjunctiva and lymph nodes as well as vascular endothelial growth factors and their receptors (VEGF-A, VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3) in the cornea.

Results  Blocking VEGF-C led to significant reductions in lymphatic caliber (P = .02) and lymphatic area (P = .006) in the corneas of mice with dry eye disease. In addition to significantly decreasing CD11b⁺ cells (P = .005), anti–VEGF-C treatment significantly decreased transcript levels of VEGF-C (P = .002), VEGF-D (P = .01), and VEGFR-3 (P = .02) in the corneas of the treated group. A significant decrease in expression of inflammatory cytokines in the conjunctiva (interleukin 1α, P = .003; interleukin 1β, P = .02; interleukin 6, P = .005) and lymph nodes (interferon , P = .008; interleukin 17, P = .003) was also seen with anti–VEGF-C treatment.

Conclusion  Treatment with anti–VEGF-C led to significant improvement in dry eye disease, reflected by a decrease in inflammation at the clinical, molecular, and cellular levels.

Clinical Relevance  Targeting prolymphangiogenic growth factors or their receptors could inhibit the trafficking of antigen-presenting cells to the draining lymph nodes and hence prove to be a potential therapeutic target for dry eye disease.

Methods  The visual fields of 468 eyes (381 patients) from the Advanced Glaucoma Intervention Study with 10 or more reliable visual field tests and 3 or more years of follow-up were studied. Starting at year 1, every other visual field examination was deleted to create a low-frequency data set, and the original group was kept as the high-frequency data set. The proportion of progressing eyes and the time to progression were compared between the 2 data sets with global and pointwise linear regression criteria.

Results  The median number of visual field examinations was 20 and 12 for the high- and low-frequency data sets, respectively. Based on primary mean deviation criteria, 204 eyes (43.6%) in the high-frequency data set and 160 eyes (34.2%) in the low-frequency data set progressed (P < .001), whereas 185 eyes (39.5%) in the high-frequency data set and 167 eyes (35.7%) in the low-frequency data set progressed according to pointwise linear regression (P = .02). The high-frequency data set was more likely to detect progression with mean deviation (hazard ratio [HR], 1.69 [95% confidence interval {CI}, 1.36-2.10]) or pointwise linear regression criteria (HR, 1.52 [95% CI, 1.21-1.90]). A similar number of improving eyes were detected with mean deviation criteria (HR, 0.95 [95% CI, 0.58-1.60]), but pointwise linear regression criteria were more likely to detect improvement in the high-frequency data set (HR, 2.27 [95% CI, 1.43-3.62]). The results did not significantly change after censoring data at 5 years.

Conclusions  Increasing the frequency of visual field testing leads to earlier detection of glaucoma progression, especially with global trend analyses. This finding has significant implications for the care of patients with glaucoma.

Methods  To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC+IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC+IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea.

Results  The RGC+IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman  = 0.71-0.74). Agreement was worse (0.53-0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC+IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°.

Conclusion  In the central 7.2°, local RGC+IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement.

Methods  There was an observational case series (Amsterdam group) and a prospective interventional case series (Mayo group). Corrected distance visual acuity (CDVA), straylight, and corneal thickness were measured in patients with phakic and pseudophakic eyes with Fuchs dystrophy recruited at the Academic Medical Center, Amsterdam, the Netherlands (99 eyes), and at Mayo Clinic, Rochester, Minnesota (48 eyes). The Mayo group was also examined at 1, 3, 6, and 12 months after DSEK; all these eyes were rendered pseudophakic during DSEK.

Results  Eyes with Fuchs dystrophy had decreased CDVA (mean [SD], 0.42 [0.26] logMAR; Snellen equivalent 20/53) and increased straylight (mean [SD], 1.54 [0.24] logarithm of the straylight parameter) compared with normal eyes. Younger patients were affected more by increased straylight than by decreased CDVA. Corrected distance visual acuity (r = 0.26; P = .003; n = 135) and straylight (r = 0.26; P = .003; n = 133) were correlated with corneal thickness. Corrected distance visual acuity and straylight improved at all postoperative examinations (P < .001), and improvement in straylight from before DSEK to 12 months after DSEK correlated with recipient age (r = –0.43; P = .01; n = 33). Improvement in straylight was more predictable than that of CDVA and was associated with preoperative straylight more than 1.33 logarithm of the straylight parameter.

Conclusions  Quality of vision is severely impaired in patients with Fuchs dystrophy and improves significantly after DSEK. Straylight improves more in younger than in older eyes after DSEK. Preoperative straylight can be a useful clinical metric to predict postoperative improvement, especially in cases where preoperative visual acuity is close to 20/20.

Methods  We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial.

Results  The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component.

Conclusions  We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

Methods  Fifteen volunteers were recruited. Each volunteer was positioned over an open blood agar plate and did the following: read a 5-minute script with a face mask, read a 5-minute script without a face mask, read a 5-minute script with the face turned away from the plate without a face mask, and stood in silence for 5 minutes. Each volunteer then read a 5-minute script while reclined in a standard ophthalmic examination chair with an open blood agar plate secured to the forehead to simulate bacterial dispersal associated with a talking patient. Total numbers of colony-forming bacteria per plate were counted, and the bacteria were identified.

Results  Significantly less bacterial growth occurred in the face mask and silence conditions compared with the no face mask condition (both P < .001). Bacterial growth was significantly greater in the reclined condition compared with the room control (P = .02). Oral streptococcal species represented 66.7% to 82.6% of bacterial colonies in the no face mask, face turned, and reclined conditions.

Conclusions  During simulated intravitreous injection, wearing a face mask or remaining silent significantly decreases culture plate contamination from talking. Talking from above and talking in the reclined position were associated with a significant increase in culture plate contamination. Physicians performing intravitreous injections should be aware of these patterns of bacterial contamination, should consider either wearing a face mask or minimizing speech, and should encourage patients to minimize speech during the procedure.

Methods  We evaluated 1059 infants born before week 28 of gestation for ROP. Infants were classified as having early (postnatal week 1) or late (weeks 2-4) definite (culture-proven) or presumed (antibiotics taken for >72 hours despite negative blood culture results) bacteremia. Severe ROP was defined as stage 3 to 5, zone 1, prethreshold/threshold, or plus disease. We used time-oriented risk models to adjust for confounders.

Results  In univariable, but not multivariable, analysis, newborns with presumed early bacteremia were at increased risk for plus disease (odds ratio [OR], 1.7; 95% CI, 1.1-2.7), and those with definite early bacteremia were at increased risk for stage 3 to 5 disease (1.9; 1.1-3.2). Infants who had presumed or definite late bacteremia were at increased risk for all 4 indicators of severe ROP in univariable analysis. In multivariable analysis, newborns with presumed late bacteremia were at increased risk for prethreshold/threshold ROP (OR, 1.8; 95% CI, 1.02-3.2), and those with definite late bacteremia were at increased risk for prethreshold/threshold ROP (1.8; 1.1-2.9) and plus disease (1.8; 1.05-2.9).

Conclusions  Definite late neonatal bacteremia seems to be an independent risk factor for prethreshold/threshold ROP and plus disease, and presumed late bacteremia seems to be related to prethreshold/threshold ROP.

Methods  Eight patients with molecularly proved BPES underwent high-resolution surface-coil 3-T magnetic resonance imaging before surgical intervention. The features of LPS muscle and adjoining connective tissue were compared with an age-matched control subject. During LPS resection for ptosis repair, detailed anatomic examination of the LPS was performed. Histopathologic characteristics were compared with normal control samples from a cadaver and a patient with simple severe congenital ptosis.

Results  The most striking feature shown on magnetic resonance imaging was the thin, long anterior part of the LPS. During the operation, this consisted of a disorganized, thin, long aponeurosis. However, in the posterior part of the LPS, there was an organized thick structure suggestive of a muscle belly. Histopathologic examination revealed posteriorly well-formed striated muscle fibers in all patients with BPES but not in the control sample from the patient with simple severe congenital ptosis. These striated muscle fibers were comparable to those of the normal control tissue but were more intermixed with collagenous tissue and little fatty degeneration.

Conclusions  The presence of striated muscle fibers in LPS of patients with BPES contrasts with the fatty degeneration in patients with simple severe congenital ptosis. To our knowledge, this is the first study providing novel insights into the pathogenesis of the eyelid malformation in BPES through extensive imaging, anatomic study, and histopathologic testing in a unique cohort of patients with molecularly proved BPES.

Methods  The study consisted of 125 consecutive patients who sought treatment from January 1, 2008, through December 31, 2010, for vertical strabismus of various causes: skew deviation (25 patients), trochlear nerve palsy (58 patients), restrictive causes (14 patients), and other causes (eg, myasthenia gravis and childhood strabismus) (28 patients). Twenty healthy participants served as controls. The deviation was measured by the prism and alternate cover test using a near target at 1/3 m in both the upright and supine positions. A vertical strabismus that decreased by 50% or more from the upright to supine position constituted a positive test result.

Results  The upright-supine test result was positive in 20 of 25 patients with skew deviation (sensitivity, 80%) but negative in all patients with trochlear nerve palsy, restrictive, or other causes (specificity, 100%).

Conclusions  The upright-supine test is highly specific for differentiating skew deviation from other causes of vertical strabismus. This test could be added as a fourth step after the 3-step test, and if the result is positive, neuroimaging should be considered if indicated clinically.

Methods  The medical records of patients with uveal melanoma evaluated at Memorial Sloan-Kettering Cancer Center from January 1998 to September 2009 were reviewed. Inclusion criteria were biopsy-proven liver metastasis and CT scan images available within 2 months of biopsy. Exclusion criteria were prior systemic or liver-directed therapy for uveal melanoma. Statistical analyses were carried out using the t test, ² test, and Kaplan-Meier log-rank analyses.

Results  Of 505 medical records reviewed, 76 were selected for study. Characteristic CT findings included multiple (68 patients [90%]), hypodense (100%), heterogeneous (100%), and enhancing (100%) hepatic lesions with a mean dominant lesion size of 46.8 cm². Eighteen patients (24%) exhibited hepatomegaly. Predominant lesion size larger than 100 cm², hepatomegaly, and ascites correlated with a lower survival rate (P = .008, P < .001, and P < .001, respectively). Radiographic evidence of extrahepatic metastases was present in 40 patients (53%). However, the presence of extrahepatic metastases did not affect survival. The results of at least 1 liver function test were abnormal in 46 of 67 patients (69%), and elevation of at least 1 serum transaminase and elevation of alkaline phosphatase were associated with larger lesions (P = .009 and P = .004, respectively) and hepatomegaly (P < .001 for both).

Conclusions  Radiographic evidence of predominant lesion size larger than 100 cm², hepatomegaly, and ascites—but not radiographic evidence of extrahepatic metastases—correlate with a lower survival rate in patients with biopsy-proven hepatic metastases of uveal melanoma.

Methods  Using immunohistochemistry and confocal microscopic analysis, we evaluated the relative numbers of inflammatory cell types in the single available clinical specimen of early NAION (21 days after event). We correlated this with the temporal inflammatory response occurring in optic nerve tissue at different times following pNAION induction.

Results  In pNAION, there is a previously unsuspected infiltration of polymorphonuclear leukocytes occurring almost immediately after infarct induction, followed by invasion of ED1+ extrinsic macrophages, which peaks 5 weeks after infarct. Intrinsic microglia accumulate up to 70 days after induction in the area of primary axonal loss. The analyzed human NAION specimen was similar to 21-day pNAION tissue, with extrinsic macrophages and intrinsic microglial cells in the region of focal axon loss.

Conclusions  Cellular inflammation plays a major early role following white-matter (optic nerve) infarct, with both polymorphonuclear leukocyte and macrophage function involved in debris elimination and tissue remodeling. The optic nerve in NAION and its primate model are associated with early cellular inflammation, previously unsuspected, that may contribute to postinfarct optic nerve damage.

Methods  African Americans aged 65 years or older who had not had a DFE in at least 2 years were recruited from community settings. Participants were randomized to receive either a tailored or targeted newsletter. Telephone follow-up was conducted at 1, 3, and 6 months to ascertain eye examination status. All participant-reported DFEs were confirmed by contacting their eye doctor (optometrist or ophthalmologist) by telephone.

Main Outcome Measure  Eye doctor–confirmed DFE at 6 months.

Results  Of the 329 participants enrolled, 128 (38.9%) had an eye doctor–confirmed DFE. No significant difference was noted in this measure by intervention group (relative risk, 1.07; 95% confidence interval, 0.82-1.40), with 66 participants in the tailored group (40.2%) and 62 participants in the targeted group (37.6%) having an eye doctor–confirmed DFE. Based on logistic regression analysis, reading the newsletter (odds ratio, 1.76; 95% confidence interval, 1.08-2.87) and planning to make an appointment for a DFE (odds ratio, 2.46; 95% confidence interval, 1.42-4.26) were significant predictors for DFE.

Conclusions  The tailored and targeted interventions were equally effective in promoting eye doctor–confirmed DFEs at 6 months. Given the increased cost and effort associated with tailoring, our results suggest that well-designed targeted print messages can motivate older African Americans to get DFEs.

Trial Registration  clinicaltrials.gov Identifier: NCT00649766

Methods  In this retrospective, noncomparative, interventional case series, 6 different surgeons performed 4509 PPV procedures from August 1, 2005, through May 31, 2010, with 1-port vitrectomy using a miniaturized multifunction probe (the Intrector).

Results  Complications were reported in 20 eyes (0.44%). Culture-positive endophthalmitis occurred in 2 eyes (0.04%), sterile endophthalmitis occurred in 6 eyes (0.13%), intraoperative or postoperative retinal detachment occurred in 4 eyes (0.09%), and vitreous hemorrhage occurred in 8 eyes (0.18%). None of the 20 eyes with complications of 4509 total eyes had worse visual outcomes than preoperative visual acuity.

Conclusion  One-port vitrectomy using the Intrector is a procedure that can be used efficiently for selected cases that do not require membrane peeling.

Methods  A retrospective interventional series in which 17 patients were treated with ophthalmic artery injection of melphalan, 5 mg, was undertaken to determine retinoblastoma control.

Results  Of 190 children with retinoblastoma, 17 (9%) were treated with IAC. Catheterization was successful in 37 of 38 attempts. The treatment was primary in 13 cases (1 failed catheterization) and secondary in 4. The median retinoblastoma base was 20 mm and the median retinoblastoma thickness was 9.0 mm. Iris neovascularization was present in 5 cases. Following IAC, complete response of the main tumor was found in 14 cases (88%) and partial response was found in 2 (12%). Eyes with complete response and followed up for a minimum of 1 year (n = 10) showed no solid tumor recurrence. Of 11 eyes with subretinal seeds, 9 (82%) had complete response, 1 (9%) had partial response, and 1 (9%) had recurrence. Of 9 eyes with vitreous seeds, 6 (67%) had complete response, 2 (22%) had partial response, and 1 (11%) had recurrence. Globe salvage was achieved in 8 of 12 eyes (67%) treated with primary IAC, including 2 of 2 group C eyes, 4 of 4 group D eyes, and 2 of 6 group E eyes according to the International Classification of Retinoblastoma. Globe salvage was achieved in 2 of 4 eyes (50%) treated secondarily after failure of other methods.

Conclusions  Of 12 eyes managed with IAC as primary treatment, globe salvage was achieved in 67%. Eyes classified as group C or D showed 100% globe salvage, whereas group E had 33% salvage. Of 4 eyes managed with IAC as secondary treatment, globe salvage was achieved in 50%.

Methods  A retrospective interventional series of ophthalmic artery cannulation for IAC injection (3 planned sessions at 1-month intervals) was undertaken. Thirty-eight catheterizations of 17 eyes of 17 patients were performed from September 2008 to September 2010. Fluoroscopy of the ophthalmic artery was performed before and immediately after treatment. Heparin was given during the procedure and aspirin (40 mg) was given orally for 1 week. The treatment complications were determined.

Results  Only 17 of 190 children were selected for treatment with IAC during this period. Following successful ophthalmic artery cannulation in 16 cases, there was no evidence of metastasis, stroke, brain injury, or persistent systemic toxic effects. Fluoroscopy demonstrated patent ophthalmic artery immediately before and after IAC injection in each case. Following therapy, orbital and adnexal findings at 1 month included eyelid edema (n = 13), blepharoptosis (n = 10), cilia loss (n = 1), and orbital congestion with temporary dysmotility (n = 12). These findings resolved within 6 months in all cases. Following therapy, vascular findings included ophthalmic artery stenosis (permanent in 3 cases, temporary in 1 case), confirmed on fluoroscopy in 3 cases. Concomitant central or branch retinal artery occlusion was noted (permanent in 2 cases, temporary in 1 case). Subtle retinal pigment epithelial mottling in 9 cases that slowly evolved to later-onset underlying choroidal atrophy in 5 cases was noted.

Conclusions  Treatment with IAC for retinoblastoma can lead to mild and severe short-term ocular complications, including eyelid edema as well as potentially blinding vascular obstruction. This procedure should be used with caution.

Methods  Retrospective histopathologic analysis of 8 eyes.

Results  The eyes were enucleated for tumor viability (n = 4), neovascular glaucoma (n = 2), anaphylactic reaction from IAC (n = 1), and persistent retinal detachment with poor visualization of the tumor (n = 1). Of the 2 eyes judged clinically with complete tumor regression and the 5 with viable tumor, the findings were confirmed on histopathology. The Rb response ranged from minimal (n = 1) to moderate (n = 1) to extensive (n = 4) to complete regression (n = 2). Viable vitreous seeds (n = 4 eyes), invasion into the optic nerve (n = 3), reaching the lamina cribrosa in 2 cases, and invasion into the choroid (n = 1) were observed. Histopathologic evidence of ischemic atrophy involving the outer retina and choroid was found in 4 eyes. One eye treated at another center with IAC and enucleated by our team for recurrence was observed to have extensive choroidal and outer retinal atrophy. This case showed orbital vascular occlusion and subendothelial smooth muscle hyperplasia. Intravascular birefringent foreign material was observed in 5 cases within occluded vessels, stimulating a granulomatous inflammatory response. The foreign material comprised cellulose fibers (n = 3), synthetic fabric fibers (n = 1), or unknown composition (n = 2). Thrombosed blood vessels were identified in 5 eyes and involved ciliary arteries in the retrobulbar orbit (n = 5), scleral emissarial canals (n = 1), small choroidal vessels (n = 1), and central retinal artery (n = 1).

Conclusion  Retinoblastoma can be controlled with IAC, but histopathology of enucleated eyes reveals that ocular complications including thromboembolic events can occur.

Purpose  To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma.

Methods  Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea and optic nerve involvement.

Results  Of 51 consecutive patients with high-risk retinoblastoma, there were 30 males (59%) and 21 females (41%), with a median age of 28 months at diagnosis. All 52 eyes were classified as group E. The main histopathologic risk factors included anterior segment invasion (7 [13%]), isolated massive posterior uveal invasion of 3 mm or greater (6 [12%]), isolated postlaminar optic nerve invasion (15 [29%]), or any posterior uveal invasion with any optic nerve involvement (24 [46%]). There was additional invasion into the sclera (3 [6%]) and extrascleral structures, including the orbit (1 [2%]). A single histopathologic high-risk factor was present in 32 eyes (62%), whereas 20 eyes (38%) manifested 2 or more high-risk characteristics. Based on previously published series, untreated high-risk retinoblastoma carries at least a 24% risk for metastatic disease. In the present series, using vincristine, etoposide, and carboplatin in all cases, there was no metastasis during a mean follow-up of 66 months (median [range], 55 [12-202] months).

Conclusions  Retinoblastoma with invasion into the postlaminar optic nerve and/or posterior uvea is at high risk for metastasis and death. In this study, postenucleation chemotherapy using vincristine, etoposide, and carboplatin was effective in preventing metastasis in every case (100%).

Methods  The multidisciplinary team included pediatric oncologists, an ophthalmologist, an ophthalmic pathologist, a geneticist, and genetic counselors. Retrospective data from 8 years included 90 initial evaluations, of which 81 probands were diagnosed with retinoblastoma (34 bilateral and 47 unilateral) and 9 were evaluated because of a positive family history.

Results  Genetic testing was accomplished equivalently in bilateral and unilateral cases in 51 of 81 patients (63%). In 5 of 30 patients (17%), with unilateral disease an RB1 mutation was identified in peripheral blood samples. In another 7 of 30 patients (23%), mutation analysis confirmed the occurrence of sporadic retinoblastoma. Overall, genetic testing of 48 at-risk family members from 21 families revealed 6 individuals positive and 42 negative for the familial mutation.

Conclusions  Our study emphasizes that genetics can be incorporated into the management plan of all retinoblastoma patients using a team approach to ensure timely evaluations and appropriate counseling. Genetic evaluations improved risk prediction for patients and family members as well as prevented overutilization of clinical screening tests, which had potential morbidity for relatives documented to not carry an RB1 mutation.

Methods  Descemet membrane endothelial keratoplasty was performed in 200 patients with Fuchs endothelial dystrophy or bullous keratopathy. Best-corrected visual acuity, subjective and objective refractive outcome and stability, and endothelial cell density were evaluated at 1, 3, and 6 months postoperatively, and intraoperative and postoperative complications were documented.

Results  At 6 months, 94% reached a best-corrected visual acuity of 20/40 or better (≥0.5); 77%, 20/25 or better (≥0.8); 47%, 20/20 or better (≥1.0), and 16%, 20/17 or better (≥1.2) (n = 159). The preoperative to 6 months' postoperative spherical equivalent showed a mean (SD) +0.38 (1.2) diopter hyperopic shift (P = .001) that correlated with a decrease in central corneal thickness (n = 143) (P = .047). Two-thirds of eyes showed refractive stability at 3 months. Donor endothelial cell density showed a decrease from mean (SD) 2560 (186) cells/mm² preoperatively to 1690 (520) cells/mm² at 6 months after surgery (n = 173) (P < .001). Graft detachment was the main complication and occurred in 18 eyes (9%). Recipient Descemet membrane remnants were present in 12 eyes (6%). Secondary glaucoma was seen in 8 eyes (4%), of which 4 showed air-bubble dislocation behind the iris. In 2 of 33 phakic eyes (6%), a secondary cataract developed requiring phacoemulsification.

Conclusions  Descemet membrane endothelial keratoplasty may offer complete visual rehabilitation within 1 to 6 months after surgery in a majority of eyes. Similar to earlier keratoplasty techniques, Descemet membrane endothelial keratoplasty may be associated with a one-third decrease in donor endothelial cell density in the early postoperative phase. Incidence of (partial) graft detachment stabilized at about 5% but could be further reduced by patient selection and/or technique modification.

Trial Registration  clinicaltrials.gov Identifier: NCT00521898

Methods  Prospective comparative case series of 718 eyes (500 patients) and 260 eyes (195 patients) that had trabeculectomy and Molteno implants, respectively, at Dunedin Hospital as the first drainage operation for primary open-angle glaucoma between 1976 and 2007, and followed up for a mean of 7.7 (range, 0.0-28.0) and 5.0 (range, 0.0-27.4) years, respectively.

Results  The probability of intraocular pressure (IOP) control at 21 mm Hg or less following trabeculectomy at 1, 2, 5, 10, 15, and 20 years was 0.95 (95% confidence interval [CI], 0.94-0.97), 0.93 (95% CI, 0.91-0.96), 0.89 (95% CI, 0.86-0.92), 0.82 (95% CI, 0.78-0.86), 0.74 (95% CI, 0.68-0.80), and 0.68 (95% CI, 0.59-0.77), respectively. There were 96 (13%) failures (using the >21–mm Hg definition of failure) in the trabeculectomy group by the final follow-up. The probability of IOP control at 21 mm Hg or less following Molteno implant insertion at 1, 2, 5, 10, 15, and 20 years was 0.98 (95% CI, 0.97-1.0), 0.97 (95% CI, 0.96-1.0), 0.96 (95% CI, 0.92-0.99), 0.96 (95% CI, 0.92-0.99), 0.91 (95% CI, 0.81-1.00), and 0.91 (95% CI, 0.81-1.00), respectively. In the Molteno implant group, there were 8 (3%) failures (using the >21–mm Hg definition of failure) by the final follow-up.

Conclusion  Insertion of a Molteno implant provided superior IOP control to trabeculectomy when carried out as a first operation in cases of primary glaucoma.

Methods  A meta-analysis of individual subject data from 4 recently completed randomized amblyopia treatment trials was performed to evaluate the relationship between age and improvement in logMAR amblyopic eye visual acuity. Analyses were adjusted for baseline amblyopic eye visual acuity, spherical equivalent refractive error in the amblyopic eye, type of amblyopia, prior amblyopia treatment, study treatment, and protocol. Age was categorized (3 to <5 years, 5 to <7 years, and 7 to <13 years) because there was a nonlinear relationship between age and improvement in amblyopic eye visual acuity.

Results  Children from 7 to less than 13 years of age were significantly less responsive to treatment than were younger age groups (children from 3 to <5 years of age or children from 5 to <7 years of age) for moderate and severe amblyopia (P < .04 for all 4 comparisons). There was no difference in treatment response between children 3 to less than 5 years of age and children 5 to less than 7 years of age for moderate amblyopia (P = .67), but there was a suggestion of greater responsiveness in children 3 to less than 5 years of age compared with children 5 to less than 7 years of age for severe amblyopia (P = .09).

Conclusions  Amblyopia is more responsive to treatment among children younger than 7 years of age. Although the average treatment response is smaller in children 7 to less than 13 years of age, some children show a marked response to treatment.

Methods  Six adult male Rhesus macaques (Macacca mulatta) were randomly assigned to 1 of 2 treatment cohorts: melphalan (5 mg/30 mL) or carboplatin (30 mg/30 mL). Each animal underwent 3 separate SSIOAC procedures at 3-week intervals. Digital retinal images were obtained during each infusion. Intravenous fluorescein angiography was performed immediately after each procedure.

Results  All SSIOAC procedures were successfully completed. Toxicities were equally distributed between drug cohorts. Systemic toxicities included mild bone marrow suppression in all animals and anorexia in 1. One animal had greater than 50% narrowing of the treated ophthalmic artery after its second infusion. All 18 procedures (100%) resulted in pulsatile optic nerve and choroid blanching, retinal artery narrowing, and retinal edema. Of the 18 procedures, retinal artery sheathing was found during 17 (94%), and retinal artery precipitates were seen in 10 (56%); choroidal hypoperfusion was seen by fluorescein angiogram in 18 (100%).

Conclusion  Real-time ophthalmic investigations are useful and, in our nonhuman primate model, indicate prevalent, acute ocular vascular toxicities during SSIOAC.

Clinical Relevance  Real-time retinal imaging is feasible in a nonhuman primate model of SSIOAC. Application to SSIOAC in children may shed insight into reported vascular toxicities.

Methods  The morphologic features of the human aceruloplasminemic retina were studied with light and electron microscopy. Retinal iron accumulation was assessed with Perls Prussian blue staining, immunohistochemistry, and secondary ion mass spectrometry.

Results  Light and electron microscopic analysis revealed several ocular pathologic findings that resembled age-related macular degeneration, including retinal pigment epithelium (RPE) depigmentation, atrophy and hypertrophy, nodular and diffuse drusen, and lipofuscin and melanolipofuscin granules. Complement deposition was detected in drusen. The RPE cells and neural retina had increased levels of iron. Two major types of RPE cells were observed: melanosome rich and melanosome poor. Melanosome-rich cells had increased levels of iron and melanolipofuscin. The melanolipofuscin granules were observed in large aggregates, where some of the melanosomes were degrading. Melanosome-poor cells lacked melanosomes, melanolipofuscin, and lipofuscin but contained electron-dense aggregates high in iron, phosphorus, and sulfur.

Conclusions  The findings in the aceruloplasminemic retina resemble some of those found in age-related macular degeneration. Also, they suggest that melanosomes in the RPE can be degraded via iron-mediated reactive oxygen species production.

Clinical Relevance  Mechanisms underlying the pathologic mechanisms found in aceruloplasminemia also may be important in age-related macular degeneration.

Methods  Comprehensive ophthalmic testing included visual acuity, static visual field, kinetic visual field, dark adaptometry, full-field electroretinography, spectral-domain optical coherence tomography, and fundus photography. Longitudinal visual function data (range, 15-27 years) were available for some of the affected individuals.

Results  We report a phenotypic assessment of 3 unrelated families, each harboring different KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). The fundi showed classic signs of RP. Best-corrected visual acuity was 20/50 or better in at least one eye up to age 65 years. Static and kinetic visual fields showed concentric constriction to central 10° to 20° by age 65 years; 2 patients with Goldmann perimetry exhibited bilateral visual field retention in the far periphery. Both rod and cone full-field electroretinographic amplitudes were substantially lower than normal, with a decline rate of 3% per year in cone 31-Hz flicker response. Rod and cone activation and inactivation variables were abnormal. Spectral-domain optical coherence tomography indicated retention of foveal inner segment–outer segment junction through age 65 years.

Conclusions  Mutations in KLHL7 are associated with a late-onset form of autosomal dominant retinal degeneration that preferentially affects the rod photoreceptors. Full-field electroretinographic findings, including recovery kinetics, are consistent with those observed in other forms of autosomal dominant RP.

Clinical Relevance  The phenotypes are similar among patients with 3 types of KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). Strong retention of foveal function and bilateral concentric constriction of visual fields with far periphery sparing may guide mutation screening in autosomal dominant RP.

Methods  Retrospective noncomparative case series comprising 17 patients (17 eyes) with partial limbal deficiency (≤50%) secondary to ocular alkali burns (11 eyes) or acid burns (6 eyes). Recipient eyes were treated by removing the conjunctivalized pannus. Superior limbal grafts (mean length, 3-5 clock hours) from HLA antigen–matched living-related donors were transplanted into deficient areas of recipient eyes. No recipients received systemic cyclosporin A therapy. Main outcome measures included corneal reepithelialization, reduction in vascularity, improved corneal clarity, and best-corrected visual acuity.

Results  All eyes achieved epithelialization a mean (SD) of 10.1 (1.9) days after surgery. Corneal reepithelialization, reduction in vascularity, and improved corneal opacity were seen in all eyes. No eyes demonstrated recurrent epithelial defects or fibrovascular tissue, but gradual recurrence of peripheral corneal vascularization was observed in 7 eyes during the follow-up period. Allograft rejection developed in 3 eyes (17.6%), all of which were successfully treated. Best-corrected visual acuity improved in all eyes, and 10 eyes (58.8%) had achieved best-corrected visual acuity of 0.5 or better (≥20/10 Snellen) at the last follow-up visit.

Conclusions  Transplantation of limbal tissue from live-related donors successfully reconstructed the ocular surface. Long-term graft survival in patients with partial limbal deficiency secondary to ocular chemical burns can be accomplished without the use of systemic immunosuppression.

Methods  All cases of lacrimal gland lymphoma from January 1, 1975, through December 31, 2009, were retrieved from The Danish Registry of Pathology. Histologic specimens were reevaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed lymphoma were collected.

Results  Twenty-seven patients with lacrimal gland lymphoma were identified. Eight of the patients were men and 19 were women; the median (range) age was 69 (43-87) years. The distribution of lymphoma subtypes was as follows: extranodal marginal zone lymphoma, 10 (37%); follicular lymphoma, 5 (19%); diffuse large B-cell lymphoma, 4 (15%); mantle cell lymphoma, 3 (11%); chronic lymphocytic leukemia/small lymphatic lymphoma, 2 (7%); and unclassified B-cell lymphoma, 3 (11%). Twenty-two patients (81%) had stage I or II lymphoma, 1 patient (4%) had stage III lymphoma, and 4 patients (15%) had stage IV lymphoma. Patients with stage I or II lymphoma were treated with radiotherapy (15 [67%]), chemotherapy (3 [14%]), chemotherapy plus radiotherapy (1 [5%]), and surgery (3 [14%]). Patients presenting with stage III or IV lymphoma were treated with chemotherapy alone. Complete remission was observed in 23 of the patients (85%), although 12 (44%) of these had a relapse, independent of subtype, stage, or treatment. The 5-year overall survival was 70%.

Conclusions  Malignant lymphoma of the lacrimal gland is relatively rare and is mostly prevalent in elderly women. The distribution of lacrimal gland lymphoma subtypes resembles that of lymphoma subtypes of the salivary glands. The majority of lacrimal gland lymphomas are low grade, and the prognosis is relatively good.

Methods  In this prospective study, subjects underwent phacoemulsification with foldable lens implantation. Anterior chamber angle grading of 2 or less (Shaffer grading) in 3 or all quadrants was considered narrow angle (NA). Anterior segment optical coherence tomography and tonometry were performed preoperatively and 10 days and 1, 3, and 6 months after surgery. The ACD and angle opening distance at 500 μm anterior to the scleral spur (AOD500) were assessed from anterior segment optical coherence tomography.

Results  Data were collected from 63 eyes that underwent cataract surgery. Twenty-six eyes were classified as having NA. Before surgery, the mean (SD) AOD500 and ACD in the NA group were 0.179 (0.014) mm and 2.23 (0.07) mm, respectively. Six months after surgery, the mean (SD) AOD500 and ACD in the NA group were 0.389 (0.025) mm and 3.75 (0.05) mm, respectively. The postoperative IOP was reduced significantly in both groups. We found that each 0.1-mm increase in AOD500 corresponded to a mean (SD) 0.42 (0.18)–mm Hg decrease in IOP (P < .001) in the NA group and 0.32 (0.16) mm Hg (P = .046) in the OA group.

Conclusions  Postoperative reduction in IOP was proportional to the increase in angle in both groups, but the IOP reduction per 0.1-mm increase in AOD500 in NA eyes was greater than that in OA eyes.

Methods  A retrospective, consecutive case series of patients presenting to a tertiary referral center in southern Ethiopia during a 13-month period. All patients underwent clinical examination, were diagnosed as having cataract on the basis of standard clinical assessment, and immediately underwent surgical management. Visual acuity results were grossly divided into ambulatory and nonambulatory vision according to patient age and cooperation.

Results  Ninety-one eyes of 73 consecutive patients (57 boys and 16 girls) were included in the study. The mean (SEM) age at diagnosis was 7.1 (0.5) years (range, 0.5-15 years). Fifty-five patients had unilateral cataract and 18 had bilateral cataract. Cataracts were categorized according to the etiologic cause: congenital (n = 50), traumatic (n = 33), congenital glaucoma-related (n = 3), partially absorbed cataracts (n = 3), and congenital rubella infections (n = 2). At presentation, visual acuity ranged from 6/60 to light perception, with 13 eyes (14%) having ambulatory vision (better than hand motion). The mean postoperative visual acuity was significantly improved, ranging from light perception to 6/9. Seventy-five eyes (82%) achieved ambulatory vision. Of the 61 eyes with an implanted intraocular lens, 56 (92%) reached ambulatory visual acuity following surgery. This was significantly greater than preoperative visual acuity results (P < .001).

Conclusions  The underlying cause and management of pediatric cataracts in the developing world can differ significantly from that commonly reported in the literature. The effects of appropriate intervention on both visual outcome and associated survival statistics may be profound.

Methods  One hundred eight glaucoma patients and 38 control patients were enrolled in the study. Eighty-six patients were classified as having normal tension glaucoma and 22 patients as having primary open-angle glaucoma. All patients underwent a complete ophthalmic examination and then a physical examination (in the rheumatology department) and were questioned regarding a history of systemic symptoms. Nailfold capillaroscopy was performed, and the results were analyzed by a single observer in a masked manner. Both the ² test and multivariate logistic regression analysis were performed to determine which ocular characteristics were associated with the findings of nailfold capillaroscopy.

Results  In the glaucoma patients, 55.6% showed dilated vessels, 35.2% showed loss of capillaries, and 19.4% showed nail bed hemorrhages by nailfold capillaroscopy. Disc hemorrhage was significantly associated with avascular area (odds ratio, 11.13; P < .001) and nail bed hemorrhage (81.59; P < .001). By multivariate logistic regression analysis, avascular area and nail bed hemorrhage continued to be independently associated with the presence of disc hemorrhages in glaucoma patients. No significant differences of association were found between patients having normal tension glaucoma and those having primary open-angle glaucoma.

Conclusions  Nailfold capillaroscopy may give valuable information about some features of patients with glaucoma. Nail bed hemorrhage and loss of nail capillaries were strongly associated with the presence of optic disc hemorrhage, and the association was stronger with nail bed hemorrhage. No differences were observed between patients with normal tension glaucoma and patients with primary open-angle glaucoma.

Methods  Twenty eyes of 19 patients were evaluated in a prospective, observational case series. Examination using IVCM and measurement of IOP were performed 15 minutes before and 15 minutes after Nd:YAG goniopuncture.

Results  Two groups could be distinguished on the basis of morphologic characteristics of the TDM before goniopuncture. In group 1 (13 eyes), the TDM was characterized by the presence of an area of epithelial cells in the deep stromal level. After goniopuncture, an opening at the TDM with dispersed epithelial cells was visible. In group 2 (7 eyes), fibrotic tissue overlying the TDM was observed in all cases, and no openings were visible after goniopuncture. Group 1 had a statistically significant decrease in mean (SD) IOP after goniopuncture (21.6 [4.8] mm Hg before and 13.5 [4.6] mm Hg after, P = .008); there was no significant change in group 2 (19.2 [4.3] mm Hg before and 20.8 [7.5] mm Hg after, P = .30). There was a strong correlation between the presence of fibrous tissue and percentage of IOP lowering after goniopuncture ( = –0.89, P < .001).

Conclusions  The presence of fibrotic tissue covering the TDM is associated with failure of goniopuncture. Use of IVCM may be valuable in predicting the efficacy of goniopuncture in patients with elevated IOP after deep sclerectomy with collagen implant.

Methods  We reviewed the medical records and clinical photographs of 26 patients seen at 5 centers in Turkey and Belgium between March 16, 2006, and July 6, 2010. Observation procedures included clinical examination, anterior segment color photography, gonioscopy, laser flare photometry, and pupillometry.

Results  All 26 patients (20 women and 6 men; mean [SD] age, 43.2 [10.5] years) had bilateral involvement. Twenty-three patients (88%) had acute-onset disease with severe photophobia and red eyes. Nineteen patients (73%) had a preceding flulike illness and used systemic antibiotics, including moxifloxacin. Diagnostic laboratory workup was unremarkable. There was pigment discharge into the anterior chamber, and flare was elevated in the absence of inflammatory cells. Most patients had severe diffuse transillumination of the iris and mydriatic distorted pupils. Pupillometry revealed a compromised reaction to light. The most serious complication was an intractable early rise in intraocular pressure. Gonioscopy revealed heavy pigment deposition in the trabecular meshwork. Although symptoms were relieved promptly by application of topical corticosteroid, the median duration of pigment dispersion was 5.25 months.

Conclusions  Bilateral acute iris transillumination with pigment dispersion and persistent mydriasis is a new clinical entity that is not an ocular adverse effect of oral moxifloxacin treatment, as previously suggested. The etiopathogenesis of this entity remains to be elucidated.

Methods  Retrospective observational case series. The medical records of 12 patients (13 eyes) with focal choroidal excavation were reviewed. Clinical histories and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and enhanced depth imaging spectral-domain optical coherence tomography) were analyzed.

Results  The mean age of the patients was 45 years (range, 22-62 years). Four patients were Asian. Mean visual acuity was 20/31 (range, 20/20 to 20/100). Mean refractive error was –3.54 diopters (D) (range, 6.00 to –8.00 D). One patient had bilateral involvement. All patients manifested varying degrees of foveal pigmentary changes that were usually hypoautofluorescent on fundus autofluorescence images. Fluorescein angiographic findings varied with degree of retinal pigment epithelial alterations. Indocyanine green angiography revealed relative hypofluorescence. In 7 eyes, spectral-domain optical coherence tomography revealed outer retinal layers conforming to retinal pigment epithelial alterations within the excavation. In the other 6 eyes, spectral-domain optical coherence tomography revealed a separation between the outer retina and the retinal pigment epithelium within the excavation. In 7 eyes studied with enhanced depth imaging spectral-domain optical coherence tomography, there was no evidence of scleral ectasia. Mean choroidal thickness of the uninvolved choroid was thicker than normal at 319 μm (range, 244-439 μm). All lesions remained stable except for in 1 eye, which had findings of central serous chorioretinopathy and secondary type 2 (subretinal) neovascularization.

Conclusion  Focal choroidal excavation is a newly described idiopathic entity in eyes having 1 or more focal areas of choroidal excavation. In some patients, there may be an association with central serous chorioretinopathy. Although most lesions remain stable, secondary choroidal neovascularization may occur.

Methods  Consecutive patients with stage 4 retinopathy of prematurity treated with modified 23-gauge vitrectomy were included in this medical record review. Major novel modifications included the use of a small infusion cannula, a 20-gauge blade for the creation of sclerotomies in the pars plicata, and a 23-gauge endoilluminator and vitreous cutter. Conjunctival dissection and suturing of sclerotomies were performed using this modified 3-port, 23-gauge vitrectomy technique. Anatomic success and surgical complications were analyzed.

Results  Twenty-six eyes of 17 patients were included and analyzed. The mean (SD) gestational age was 28.0 (2.5) weeks, and the mean birth weight was 1199 (449) g. Mean postmenstrual age at the time of vitrectomy was 40.5 (3.0) weeks. Overall, 20 eyes (77%) achieved retinal attachment in a single operation, and 23 eyes (88%) achieved retinal attachment after multiple procedures. Postoperative complications included disc dragging (5 eyes [19%]), cataracts (4 [15%]), glaucoma (2 [8%]), persistent vitreous hemorrhage (1 [4%]), and posterior synechia (1 [4%]).

Conclusions  This 23-gauge vitrectomy system seems to be a safe and effective approach for treatment of stage 4 retinopathy of prematurity. This modified system combines the benefits of 20- and 23-gauge vitrectomy and offers safer insertion of infusion cannulas in smaller eyes, more working space in pediatric eyes, a cutting port that is closer to the retina, and a faster cutting speed with less vitreous traction during the operation.

Study Design  A retrospective consecutive case series of patients with thyroid-related orbitopathy.

Results  One hundred eighty-nine orbits from 99 patients were evaluated. Statistically significant clinical predictors of DON on univariate analysis included a difference in intraocular pressure from primary gaze to upgaze (P = .02), the presence of lagophthalmos (P = .04), and inflammation as measured by the VISA (vision, inflammation, strabismus, appearance/exposure) inflammatory scale (P = .004). Dysthyroid optic neuropathy was inversely related to the marginal reflex distance (P = .01), levator function (P = .02), total ductions (P = .003), and interpalpebral fissure (P = .04). Statistically significant radiologic predictors determined on univariate analysis included apical crowding (P < .001), presence of enlarged tendons (P = .004), increasing total rectus diameter (P = .02), and presence of small, low densities within the recti muscles (P = .04). Multivariate analysis found only total ductions (P = .02) and marginal reflex distance (P = .04) determined on clinical examination and apical crowding shown on computed tomography (P = .003) to be significantly associated with DON. Receiver operating characteristic curves were used to evaluate the ability of the clinical and radiologic assessment, as well as the combination of these assessments, to predict DON. All 3 models were strong predictors of DON, with no statistically significant differences in the area under the receiver operating characteristic curve among them (P = .14).

Conclusions  Total ductions, marginal reflex distance, and apical crowding observed on computed tomography scans are able to predict the presence of DON with high sensitivity, specificity, positive predictive value, and negative predictive value. Eyelid ptosis is a novel predictor of DON.

Methods  Using a well-described limbal laser technique, unilateral ocular hypertension was induced in 2 groups (26 per group) of Sprague-Dawley rats. One group remained normoglycemic; the other was rendered hyperglycemic by means of an intraperitoneal injection of streptozocin. After 2 weeks of elevated intraocular pressure, axonal and retinal damage profiles were compared using several histological techniques. Immunohistochemical changes in the retina and optic nerve were also assessed.

Results  We found convincing evidence of delayed axonal degeneration and retinal ganglion cell death in hyperglycemic rats. Axon loss was reduced by about 50% 2 weeks after induction of ocular hypertension. Survival of retinal ganglion cell perikarya increased to a similar extent in hyperglycemic rats.

Conclusions  The optic nerve and retinal ganglion cells are partially protected by short-term hyperglycemia in this rat model of experimental glaucoma. Energy substrate availability may therefore play a role in glaucomatous optic neuropathy.

Clinical Relevance  Our findings, to some extent, support the claims of the Ocular Hypertension Treatment Study, in which diabetes appeared to protect against the conversion to glaucoma. Targeted manipulation of neuronal energy metabolism may delay optic nerve degeneration and may represent a novel neuroprotective strategy for neurodegenerative diseases of the visual system such as glaucoma.

Methods  We analyzed glaucoma medication expenditure trends among participants of the 2001-2006 Medical Expenditure Panel Survey, a subsample of the National Health Interview Survey, which is a continuous multipurpose, multistage area probability survey of the US civilian noninstitutionalized population. After adjusting for survey design and inflation using the 2009 inflation index, data from 1404 participants 18 years and older using glaucoma medication were analyzed.

Results  Mean annual glaucoma medication expenditure per subject increased from $445 in 2001 to $557 in 2006 (slope = 20.8; P < .001). Subgroup analysis showed expenditure increased significantly in women (P = .02), those with public-only insurance (P < .001), and those with less than a high school education (P < .008). Over the survey period, a significant decrease in expenditures on β-blockers (P = .048) and significant increases in expenditures on prostaglandin analogs (P = .01) and α-agonists (P = .01) were found.

Conclusions  Factors associated with increasing glaucoma medication expenditure trends include the increasing use of prostaglandin analogs, changes in insurance coverage, and possibly more aggressive glaucoma treatment. The findings are pertinent to the development of cost-effective strategies that optimize treatment and reduce expenditures.

Methods  Affected individuals in the families underwent a detailed ophthalmological examination that consisted of fundus photography and electroretinography. Blood samples were collected from all participating family members, and genomic DNA was extracted. A genome-wide linkage scan was performed, followed by exclusion analyses among our cohort of nuclear consanguineous families with microsatellite markers spanning the TULP1 locus on chromosome 6p. Two-point logarithm of odds scores were calculated, and all coding exons of TULP1 were sequenced bidirectionally.

Results  The results of ophthalmological examinations among affected individuals in these 5 families were suggestive of retinitis pigmentosa. The genome-wide linkage scan localized the disease interval to chromosome 6p, harboring TULP1 in 1 of 5 families, and sequential analyses identified a single base pair substitution in TULP1 that results in threonine to alanine substitution (p.T380A). Subsequently, we investigated our entire cohort of families with autosomal recessive retinitis pigmentosa and identified 4 additional families with linkage to chromosome 6p, all of them harboring a single base pair substitution in TULP1 that results in lysine to arginine substitution (p.K489R). Results of single-nucleotide polymorphism haplotype analyses were suggestive of a common founder in these 4 families.

Conclusion  Pathogenic mutations in TULP1 are responsible for the autosomal recessive retinitis pigmentosa phenotype in these consanguineous Pakistani families, with a single ancestral mutation in TULP1 causing the disease phenotype in 4 of 5 families.

Clinical Relevance  Clinical and molecular characterization of pathogenic mutations in TULP1 will increase our understanding of retinitis pigmentosa at a molecular level.