Objective  To compare the effects on visual acuity of laser treatment (LT), photodynamic therapy (PDT) with verteporfin, and intravitreal bevacizumab treatment in patients with juxtafoveal choroidal neovascularization secondary to pathologic myopia.

Methods  This prospective randomized clinical investigation enrolled 54 patients, who were divided into 3 groups receiving PDT, LT, or intravitreal bevacizumab treatment. The anti–vascular endothelial growth factor group received 1.25 mg of intravitreal bevacizumab at baseline; retreatment was performed if persistent intraretinal or subretinal fluid evaluated on optical coherence tomography or if choroidal neovascularization progression was detected on fluorescein angiography. The PDT group received treatment following the Verteporfin in Photodynamic Therapy Study Group guidelines. The LT group was submitted to direct LT and received PDT treatment if subfoveal recurrence or progression was detected on fluorescein angiography. A change in best-corrected visual acuity was the primary outcome.

Results  The mean best-corrected visual acuity in the PDT group decreased from 0.52 logMAR (SD, 0.24 logMAR) at baseline to 0.72 logMAR (SD, 0.25 logMAR) at the end of the study (P = .002). The LT group showed substantial stabilization from mean baseline visual acuity (mean, 0.45 logMAR [SD, 0.27 logMAR]) to the 24-month (mean, 0.56 logMAR [SD, 0.34 logMAR) examination values. The mean best-corrected visual acuity in the anti–vascular endothelial growth factor group increased from 0.6 logMAR (SD, 0.3 logMAR) at baseline to 0.42 logMAR (SD, 0.35 logMAR) at the end of the study (P = .006).

Conclusions  Overall, bevacizumab treatment offers the best functional results during a 2-year follow-up. In view of the small size of the sample in this study and the relatively low frequency of juxtafoveal choroidal neovascularization secondary to pathologic myopia, a multicentric clinical trial is necessary to validate our results.

Published online February 8, 2010 (doi:10.1001/archophthalmol.2009.408).

Objective  To compare the safety and efficacy of earlier vs later treatment in preventing primary open-angle glaucoma (POAG) in individuals with ocular hypertension.

Methods  One thousand six hundred thirty-six individuals with intraocular pressure (IOP) from 24 to 32 mm Hg in 1 eye and 21 to 32 mm Hg in the fellow eye were randomized to observation or to topical ocular hypotensive medication. Median time of treatment in the medication group was 13.0 years. After a median of 7.5 years without treatment, the observation group received medication for a median of 5.5 years. To determine if there is a penalty for delaying treatment, we compared the cumulative proportions of participants who developed POAG at a median follow-up of 13 years in the original observation group and in the original medication group.

Main Outcome Measures  Cumulative proportion of participants who developed POAG.

Results  The cumulative proportion of participants in the original observation group who developed POAG at 13 years was 0.22 (95% confidence interval [CI], 0.19-0.25), vs 0.16 (95% CI, 0.13-0.19) in the original medication group (P = .009). Among participants at the highest third of baseline risk of developing POAG, the cumulative proportion who developed POAG was 0.40 (95% CI, 0.33-0.46) in the original observation group and 0.28 (95% CI, 0.22-0.34) in the original medication group. There was little evidence of increased adverse events associated with medication.

Application to Clinical Practice  Absolute reduction was greatest among participants at the highest baseline risk of developing POAG. Individuals at high risk of developing POAG may benefit from more frequent examinations and early preventive treatment.

Trial Registration  clinicaltrials.gov Identifier: NCT00000125

Objective  To evaluate the safety and efficacy of a dexamethasone intravitreous drug delivery system (DDS) in eyes with diabetic macular edema (DME).

Methods  Patients with persistent macular edema (≥90 days' duration) were randomized to treatment with 700 µg or 350 µg of dexamethasone DDS or observation. One eye from each patient was designated as the study eye. The analysis is of the eyes in this study with DME (n = 171).

Main Outcome Measures  The primary outcome measure was the proportion of eyes that achieved an improvement in best-corrected visual acuity (BCVA) of 10 letters or more from baseline at day 90. Other outcome measures included fluorescein leakage, central retinal thickness, and safety parameters.

Results  At day 90, a BCVA improvement of 10 letters or more was seen in more eyes in the 700-µg group (33.3%) and 350-µg group (21.1%) than the observation group (12.3%; P = .007 vs 700-µg group). At day 180, a BCVA improvement of 10 letters or more was seen in 30% of eyes in the 700-µg group, 19% in the 350-µg group, and 23% in the observation group (P ≥ .4 for treated vs observed eyes). There were also significantly greater improvements in central retinal thickness and fluorescein leakage in treated eyes than observed eyes (P = .03; day 90). Dexamethasone DDS was well tolerated.

Conclusions  In eyes with persistent DME, treatment with 700 µg of intravitreal dexamethasone DDS is well tolerated and produces significant improvements in BCVA, central retinal thickness, and fluorescein leakage compared with observation (statistically significant at day 90).

Application to Clinical Practice  Dexamethasone DDS, 700 µg, may have potential as a treatment for persistent DME.

Trial Registration  clinicaltrials.gov Identifier: NCT00035906

Objective  To compare the effectiveness of patching plus telescopic magnification vs patching alone in treating refractory amblyopia.

Methods  Children aged 4 to 17 years who failed previous amblyopia treatment were recruited into this prospective study. Subjects were randomly assigned to either 30 minutes per day of patching of the fellow eye only (n = 7) or 30 minutes per day of patching of the fellow eye plus concurrent use of a telescope in the amblyopic eye (n = 8).

Main Outcome Measure  Best-corrected logMAR visual acuity score of the amblyopic eye after 17 weeks of treatment.

Results  Both treatment groups demonstrated significant improvement in visual acuity in the amblyopic eye after 17 weeks (P = .001). Improvements in the patching-only group were slightly greater over the course of treatment, but this difference was not statistically significant (P = .06). At 17 weeks, mean visual acuity improvement from baseline was 0.14 logMAR (SD, 0.13 logMAR) in the patching-only group and 0.06 logMAR (SD, 0.17 logMAR) in the patching plus telescope group (P = .11). The 17-week visual acuity was at least 0.2 logMAR and/or improved from baseline by at least 0.2 logMAR in 2 patients in the patching-only group and none in the patching plus telescope group (P = .08).

Conclusion  Treatment of refractory amblyopia in children using telescopic magnification did not appear to confer any additional benefits over patching alone.

Application to Clinical Practice  Occlusion and penalization remain the standard of care for patients with amblyopia and should remain the benchmark against which other treatments are compared in clinical trials for amblyopia therapy.

Trial Registration  clinicaltrials.gov Identifier: NCT00970554

Objective  To compare the complications of phacoemulsification alone vs combined phacotrabeculectomy in chronic angle-closure glaucoma (CACG) with coexisting cataract.

Methods  Patients with CACG with coexisting cataract recruited into 2 randomized controlled trials comparing phacoemulsification alone vs combined phacotrabeculectomy were pooled for analysis. The first trial recruited patients with medically controlled intraocular pressure, while the second trial recruited patients with medically uncontrolled intraocular pressure. The 2 trials had otherwise identical study designs. All patients were reviewed every 3 months for 2 years after surgery. The main outcome measure was the surgical complications of phacoemulsification alone vs combined phacotrabeculectomy in CACG eyes with cataract.

Results  One hundred twenty-three CACG eyes with cataract from 123 patients were included. Sixty-two CACG eyes were randomized to receive phacoemulsification alone, and 61 eyes had combined phacotrabeculectomy. In the phacoemulsification group, 5 of the 62 CACG eyes (8.1%) had a total of 5 surgical complications. In the combined phacotrabeculectomy group, 16 of the 61 CACG eyes (26.2%) had a total of 19 surgical complications. The difference in the proportion of eyes with 1 or more surgical complications between the 2 treatment groups was statistically significant (P = .007, Pearson ² test). There was no statistically significant difference in final visual acuity or glaucomatous progression during the 24-month follow-up.

Conclusions  Combined phacotrabeculectomy resulted in significantly more surgical complications than phacoemulsification alone in CACG eyes with coexisting cataract. There was no difference in visual acuity or disease progression between the 2 treatment groups.

Objective  To assess the cross-sectional association of thiazolidinediones with diabetic macular edema (DME).

Methods  The cross-sectional association of DME and visual acuity with thiazolidinediones was examined by means of baseline fundus photographs and visual acuity measurements from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Visual acuity was assessed in 9690 participants in the ACCORD trial, and 3473 of these participants had fundus photographs that were centrally read in a standardized fashion by masked graders to assess DME and retinopathy from October 23, 2003, to March 10, 2006.

Results  Among the subsample, 695 (20.0%) people had used thiazolidinediones, whereas 217 (6.2%) people had DME. Thiazolidinedione use was not associated with DME in unadjusted (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.71-1.44; P = .95) and adjusted (OR, 0.97; 95% CI, 0.67-1.40; P = .86) analyses. Significant associations with DME were found for retinopathy severity (P < .001) and age (OR, 0.97; 95% CI, 0.952-0.997; P = .03) but not for hemoglobin A_1c (P = .06), duration of diabetes (P = .65), sex (P = .72), and ethnicity (P = .20). Thiazolidinedione use was associated with slightly greater visual acuity (0.79 letter; 95% CI, 0.20-1.38; P = .009) of uncertain clinical significance.

Conclusions  In a cross-sectional analysis of data from the largest study to date, no association was observed between thiazolidinedione exposure and DME in patients with type 2 diabetes; however, we cannot exclude a modest protective or harmful association.

Trial Registration  clinicaltrials.gov Identifier: NCT00542178

Objective  To determine the prevalence of hepatic abnormalities identified during abdominal computed tomography (CT) performed within 1 month of the diagnosis of primary uveal melanoma.

Methods  Retrospective review of CT reports generated within 1 month following diagnosis of uveal melanoma in 91 patients at Memorial Sloan-Kettering Cancer Center, New York, New York, from 2004 to 2009.

Results  Of 198 patients reviewed, 91 (46%) had a CT scan within 1 month of uveal melanoma diagnosis; 1 or more hepatic abnormalities were identified in 50 of these patients (55%). Abnormalities included 38 focal (13 solitary, 25 multiple) and 15 diffuse (11 partial, 4 complete) lesions. Six patients had hepatic lesions suspected to be metastatic melanoma, but this was confirmed in only 3. Lesions suspected to be metastases were more likely multiple than solitary (P = .03). Thirty-nine patients had other lesions, most commonly lesions that were too small to be characterized, a fatty liver, and hepatic cysts. Lesions in 5 of 50 patients with abnormalities could not be classified. Neither the protocol (triphasic vs nontriphasic) nor the center where the scan was performed (Sloan-Kettering vs other) was significantly related to the likelihood of identifying hepatic abnormalities in a given patient (P = .46 and P = .1, respectively).

Conclusion  Although hepatic abnormalities were frequently identified in patients who underwent CT within 1 month of uveal melanoma diagnosis, metastatic disease was confirmed only in the setting of multiple lesions in only a minority of patients.

Objective  To describe the incidence of pediatric Horner syndrome and the risk of occult malignancy in a population-based cohort.

Methods  The medical records of all pediatric patients (aged <19 years) residing in Olmsted County, Minnesota, who received diagnoses of Horner syndrome from January 1, 1969, through December 31, 2008, were retrospectively reviewed.

Results  Horner syndrome was diagnosed in 20 pediatric patients during the 40-year period, yielding an age- and sex-adjusted incidence of 1.42 per 100 000 patients younger than 19 years of age (95% confidence interval [CI], 0.80-2.04). Eleven of the 20 patients (55%) had a congenital onset, for a birth prevalence of 1 in 6250 (95% CI, 3333-10 000), while the remaining 9 (45%) had acquired syndromes. Seven of the 11 (63.6%) patients with congenital cases had a history of birth trauma, while the remaining 4 (36.4%) had no identifiable cause. Six of the 9 (66%) acquired cases occurred following surgery or trauma, while the remaining 3 (33%) had no known etiology. None of the 20 patients (95% CI, 0.0%-16.8%) were found to have a neuroblastoma or other malignancy during a mean follow-up of 56.5 months (range, 0-256.9 months).

Conclusions  The incidence of pediatric Horner syndrome in this population was 1.42 per 100 000 patients younger than 19 years, with a birth prevalence of 1 in 6250 for those with a congenital onset. Birth, surgical, or other trauma occurred in 13 (65%) of the patients, while none were found to have an underlying mass lesion, suggesting a need for reappraising current recommendations for extensive evaluations in these patients.

Objective  To evaluate visual field abnormalities after an episode of optic neuritis among participants in the Optic Neuritis Treatment Trial.

Methods  Three readers independently evaluated 10 443 visual fields from 454 patients and classified visual field abnormalities into 21 different monocular categories representing 3 general types of visual loss: diffuse, localized, and artifactual. Classification frequency was determined and reader agreement was evaluated. The association of visual field abnormality classifications with mean deviation, pattern standard deviation, visual acuity, and foveal threshold was assessed.

Results  At baseline, diffuse loss accounted for 66.2% of the abnormalities in the affected eyes but only 6.2% of the abnormalities in the fellow eyes. During years 1 through 15, the affected and fellow eyes exhibited predominantly localized loss in the nerve fiber bundle region (partial arcuate, paracentral, and arcuate defects). At year 1, 35.7% of the abnormalities in the affected eyes and 34.4% in the fellow eyes consisted of localized defects. At year 15, 39.5% of abnormalities in the affected eyes and 26.3% in the fellow eyes consisted of localized defects. Foveal threshold was highly correlated with visual acuity and contrast sensitivity in the affected eye at baseline (–0.82 vs 0.79, respectively), 6 months (–0.84 vs 0.81), and 1 year (–0.84 vs 0.79).

Conclusions  Diffuse and central loss were more predominant in the affected eye at baseline, and nerve fiber bundle defects (partial arcuate, paracentral, and arcuate) were the most predominant localized abnormalities in both the affected and fellow eyes during the study.

Objective  To confirm the ocular hypotensive effects of anecortave acetate on an ovine model for steroid-induced ocular hypertension. Eyes of normal sheep exhibit a robust steroid-induced ocular hypertensive response. Recent observations in an uncontrolled, interventional case series indicated that anecortave elicited hypotensive effects when administered as a sub-Tenon depot in the eyes of a small sample of patients with glaucoma.

Methods  Intraocular pressure (IOP) was monitored by Perkins applanation tonometry in 16 normal sheep receiving topically administered prednisolone acetate, 0.5%, in both eyes, 3 times daily, a protocol that doubled IOP within 12 days. Half of the sheep had received a unilateral sub-Tenon injection of anecortave in 1 eye prior to the initiation of the bilateral prednisolone instillations, while the 8 remaining sheep received the unilateral anecortave sub-Tenon depot after the IOP was maximally elevated by the prednisolone instillations.

Results  In these 2 sets of experiments, the presence of the anecortave depot suppressed the steroid-induced IOP elevation and reverted the elevated IOP to baseline levels. Measurements of aqueous outflow facility indicated that eyes treated with prednisolone plus anecortave exhibited a 5.8-fold higher outflow facility than the fellow eyes solely exposed to prednisolone, indicating that anecortave prevented the increase in outflow resistance produced by the corticosteroid.

Conclusion  Elucidation of the mechanisms of action of anecortave in animal models may prove relevant to the design of novel interventions for the management of primary open-angle glaucoma.

Objectives  To describe a unique pattern of helicoid subretinal fibrosis associated with a novel recessive NR2E3 mutation and to highlight how examination of the proband's affected relative allowed appropriate genetic testing.

Design  Interventional family study (ophthalmic examination and candidate gene testing).

Results  The proband (mother), who complained of poor vision since early childhood, had bilateral helicoid subretinal fibrosis mostly involving the macula. Two children were symptomatic; one had ophthalmic findings similar to her mother while the second had macular retinoschisis, retinal pigment epithelium changes, and refractive accommodative esotropia. The father and third child were asymptomatic and had unremarkable ophthalmic examination findings. Based on the findings in the second symptomatic child, NR2E3 analysis was performed, which revealed homozygosity for a novel mutation, p.S44X, in all 3 affected individuals and heterozygosity for the mutation in both asymptomatic individuals.

Conclusion  Helicoid subretinal fibrosis is another potential phenotypic manifestation of recessive NR2E3 mutation.

Clinical Relevance  Examination of affected relatives can be helpful in guiding molecular genetic testing for hereditary eye disease when the proband's diagnosis is unclear.

Age-related macular degeneration (AMD) is one of the most well-characterized late-onset, complex trait diseases. Remarkable advances in our understanding of the genetic and biological foundations of this disease were derived from a recent convergence of scientific and clinical data. Importantly, the more recent identification of AMD-associated variations in a number of complement pathway genes has provided strong support for earlier, paradigm-shifting studies that suggested that aberrant function of the complement system plays a key role in disease etiology. Collectively, this wealth of information has provided an impetus for the development of powerful tools to accurately diagnose disease risk and progression and complement-based therapeutics that will ultimately delay or prevent AMD. Indeed, we are poised to witness a new era of a personalized approach toward the assessment, management, and treatment of this debilitating, chronic disease.

Objective  To evaluate patterns of care for age-related macular degeneration following the introduction of vascular endothelial growth factor inhibitors.

Methods  Using a population-based retrospective design, we studied monthly fee claims for intravitreal injections submitted to the Ontario Health Insurance Plan between January 1, 2000, and March 30, 2008, and linked procedures to the physicians who performed them. This database records physician services provided as part of universal health care insurance coverage in Ontario, Canada. This program covers all residents of Ontario, which had an average population of 12.1 million during the study period.

Results  Following regulatory approval of bevacizumab for colorectal cancer in 2005, off-label use of this drug for the treatment of retinal disease, particularly age-related macular degeneration, became increasingly common. The rate of intravitreal injections in Ontario rapidly grew 8-fold, and this growth preceded the availability of ranibizumab by more than a year. Moreover, in 2007, more than 50% of intravitreal injections in Ontario were performed by 3% of ophthalmologists.

Conclusions  The development of vascular endothelial growth factor inhibitors has revolutionized the treatment of age-related macular degeneration. To our knowledge, this study is the first to quantify the dramatic uptake of these treatments at a population level. Our findings also suggest that off-label injection of bevacizumab was highly prevalent in Ontario. Serial intravitreal injections requiring direct physician administration and the concentration of injection procedures in the hands of a small number of ophthalmologists have the potential to affect services for other vision-threatening conditions.