Archives of Opthalmology recent issues

Archives of Ophthalmology informs readers of progress, problems, and pertinent research in the practice of ophthalmology through the monthly publication of peer-reviewed original contributions and observations. Archives is one of the best-read, most-frequently cited publications in its field. Special departments provide in-depth information on new instruments, surgical techniques, socioeconomics, epidemiology and biostatistics.

Intravitreous Dexamethasone Effects on Different Patterns of Diabetic Macular Edema [Research Letters]

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Laser Photocoagulation, Photodynamic Therapy, and Intravitreal Bevacizumab for the Treatment of Juxtafoveal Choroidal Neovascularization Secondary to Pathologic Myopia [Clinical Sciences]

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).

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About This Journal [About This Journal]

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Delaying Treatment of Ocular Hypertension: The Ocular Hypertension Treatment Study [Clinical Trial]

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

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Randomized Controlled Trial of an Intravitreous Dexamethasone Drug Delivery System in Patients With Diabetic Macular Edema [Clinical Trial]

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

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Effectiveness of Telescopic Magnification in the Treatment of Amblyopia: A Pilot Study [Clinical Trial]

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

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Dr Thompson's Eye Water [Ophthalmological Ephemera]

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Phacoemulsification vs Phacotrabeculectomy in Chronic Angle-closure Glaucoma With Cataract Complications [Clinical Sciences]

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.

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Errors in Byline and Text in: Association Between Erythropoietin Gene Polymorphisms and Diabetic Retinopathy [Correction]

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Lack of Association Between Thiazolidinediones and Macular Edema in Type 2 Diabetes: The ACCORD Eye Substudy [Clinical Sciences]

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

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Hepatic Abnormalities Identified on Abdominal Computed Tomography at Diagnosis of Uveal Melanoma [Clinical Sciences]

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.

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October 2009 Archives Web Quiz Winner [Archives Web Quiz Winner]

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Incidence of Pediatric Horner Syndrome and the Risk of Neuroblastoma: A Population-Based Study [Clinical Sciences]

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.

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Visual Field Profile of Optic Neuritis: A Final Follow-up Report From the Optic Neuritis Treatment Trial From Baseline Through 15 Years [Clinical Sciences]

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.

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Suppression of Corticosteroid-Induced Ocular Hypertension in Sheep by Anecortave [Laboratory Sciences]

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.

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Helicoid Subretinal Fibrosis Associated With a Novel Recessive NR2E3 Mutation p.S44X [Ophthalmic Molecular Genetics]

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.

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Complement, Age-Related Macular Degeneration and a Vision of the Future [Mechanisms of Ophthalmic Disease]

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.

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Rapid Expansion of Intravitreal Drug Injection Procedures, 2000 to 2008: A Population-Based Analysis [Socioeconomics and Health Services]

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.

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Treatment of Ocular Hypertension: Hamlet's Lament Revisited [Editorial]

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Suppression and Reduction of Corticosteroid-Induced Ocular Hypertension by Anecortave in Sheep [Editorial]

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A Transformation in Ocular Oncology: From Megacenter to Multicenter [Editorial]

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Bilateral Superselective Ophthalmic Artery Chemotherapy for Bilateral Retinoblastoma: Tandem Therapy [Small Case Series]

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Evisceration in Unsuspected Intraocular Tumors [Small Case Series]

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Invasive Orbital Basal Cell Carcinoma [Ophthalmic Images]

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Conservative Surgical Treatment of Medulloepithelioma of the Ciliary Body [Research Letters]

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Mixed Tumor of the Choroid [Research Letters]

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Socioeconomic Status and Choroidal Melanoma in Scotland [Research Letters]

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Endogenous Streptococcus agalactiae (Group B Streptococcus) Endophthalmitis as a Presenting Sign of Precursor T-Cell Lymphoblastic Leukemia [Research Letters]

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Cystic Solitary Fibrous Tumor of the Orbit [Research Letters]

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Ophthalmic Pathology and Ophthalmology [Letters]

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Ophthalmic Pathology and Ophthalmology--Reply [Letters]

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Rupture Pressure of the Healthy Human Eye [Letters]

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About This Journal [About This Journal]

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Fixed Combination of Latanoprost and Timolol vs Individual Components for Primary Open-Angle Glaucoma or Ocular Hypertension: A Randomized, Double-Masked Study [Clinical Trial]

Objective  To assess the efficacy and safety of fixed-combination latanoprost-timolol (FCLT) vs latanoprost or timolol monotherapy.

Methods  This 12-week, randomized, double-masked, parallel-group study included patients with open-angle glaucoma or ocular hypertension treated with a β-blocker and with baseline intraocular pressure (IOP) of 26 through 36 mm Hg. Following washout, eligible patients were randomized to once-daily FCLT in the evening, latanoprost in the evening, or timolol in the morning.

Main Outcome Measures  Postbaseline IOP assessments at 8 am, 10 am, and 4 pm at weeks 2, 6, and 12; statistical superiority of FCLT for the 18 pairwise comparisons between FCLT and the 2 monotherapies, using analysis of variance.

Results  All therapies resulted in significant IOP reductions from baseline. Pairwise comparisons favored FCLT at all time points. When the 18 comparisons were tested simultaneously, FCLT was statistically superior to latanoprost at 7 of 9 time points and at all 9 time points when compared with timolol. In addition, FCLT was associated with greater percentage reductions in diurnal IOP levels and a greater likelihood of achieving lower mean diurnal IOP levels. Diurnal IOP reductions of 30% or more from baseline to week 12 were achieved by 73.5%, 57.5%, and 32.8% of those treated with FCLT, latanoprost, and timolol, respectively (P = .007 for FCLT vs timolol; P < .001 for FCLT vs latanoprost). All therapies were well tolerated.

Conclusions  Fixed-combination latanoprost-timolol therapy is as safe and effective in lowering IOP in patients with either ocular hypertension or glaucoma as monotherapy with latanoprost or timolol. Combination therapy can be used to treat patients for whom monotherapy does not provide sufficient IOP reduction.

Application to Clinical Practice  The simplicity, efficacy, and tolerability of FCLT contribute to its utility in clinical practice.

Trial Registration  clinicaltrials.gov Identifier NCT00277498

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Publishing Online Ahead of Print [Announcement]

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Immunohistochemical Studies of Conjunctival Nevi and Melanomas [Clinical Sciences]

Objective  To evaluate the role of immunohistochemical methods in the diagnosis of benign and malignant conjunctival melanocytic proliferations.

Design  Retrospective immunohistopathologic study.

Methods  Paraffin-embedded tissue sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45, and Ki-67 nuclear proliferation protein.

Results  All nevi immunostained moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were negative in the middle and lower subepithelial portions of 18 of 20 lesions; it was usually only weakly positive within the superficial junctional zone. Only 1 melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in all lesions at some level of intensity. Ki-67 positivity was restricted to the junctional zone of nevi and was diffuse in melanomas. The mean Ki-67 proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45 can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ and atypical primary acquired melanoses had more than twice the Ki-67 proliferation counts of intraepithelial junctional nevocytes (P < .001) and more intense HMB-45 cytoplasmic staining than junctional zone nevocytes.

Conclusions  S-100 and MART-1 were not useful in separating benign from malignant lesions. Results for nevus cells beneath the junctional zone were overwhelmingly negative for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB-45 (P < .001). A higher Ki-67 proliferation index convincingly separated melanomas from nevi (P < .001). Immunostaining for HMB-45 and Ki-67 are valuable adjuncts to careful histopathologic evaluation in assessing benign and malignant conjunctival melanocytic tumors.

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New Insights Into Changes in Corneal Thickness in Healthy Mountaineers During a Very-High-Altitude Climb to Mount Muztagh Ata [Clinical Sciences]

Objective  To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT).

Methods  Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO₂) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m.

Results  Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 µm. Mean CCT in group 2 increased from 534 to 563 µm (P = .048). The amount of decrease in SpO₂ paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO₂ and age.

Conclusions  Corneal swelling during high-altitude climbs is promoted by low SpO₂. Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness–related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.

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In Memoriam: Steven M. Podos, MD (1937-2009) [Obituary]

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Efficacy of Sustained Topical Dorzolamide Therapy for Cystic Macular Lesions in Patients With X-Linked Retinoschisis [Clinical Sciences]

Objective  To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with juvenile X-linked retinoschisis (XLRS).

Design  Retrospective analysis.

Setting  University hospital, tertiary care referral center.

Patients  Twenty-nine eyes of 15 patients with XLRS receiving treatment with the topical dorzolamide formulation for 4 to 41 months were enrolled.

Main Outcome Measures  Changes in visual acuity, cystic macular lesions, and central foveal zone thickness on optical coherence tomography during follow-up for the duration of treatment.

Results  Among the 15 patients with XLRS, 20 eyes (69%) of 11 patients showed a positive response to treatment. Five of the 20 eyes (25%) in 3 of the 11 patients showed an initial response and a subsequent rebound of macular cysts. In 4 eyes (14%) of 3 patients, there was no response to treatment, but the macular cysts did not worsen compared with the baseline level. In 5 additional eyes (17%) of 4 patients, there was no response to treatment, and the macular cysts worsened when compared with the baseline level. Sixteen eyes (55%) of 12 patients had improvement in best-corrected visual acuity by at least 7 letters in at least 1 eye at the most recent follow-up visit. Seventeen eyes (59%) of 10 patients showed a reduction in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level.

Conclusion  Patients with XLRS have the potential to experience a beneficial effect from sustained treatment with dorzolamide, 2%.

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Dr Thompson's Eye Water [Ophthalmological Ephemera]

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Relationship of Blood Pressure to Retinal Vessel Diameter in Type 1 Diabetes Mellitus [Clinical Sciences]

Objective  To examine the relationship of blood pressure (BP) and use of angiotensin-receptor blocker or angiotensin-converting enzyme inhibitor to retinal vessel diameter in normotensive, normoalbuminuric persons with type 1 diabetes mellitus.

Methods  In a randomized, controlled clinical trial, clinic and 24-hour ambulatory BPs were measured in persons with type 1 diabetes mellitus and gradable fundus photographs both at baseline (n = 147) and at 5-year follow-up (n = 124). Retinal arteriole and venule diameters were measured by a computer-assisted technique. Individual arteriole and venule measurements were combined into summary indexes that reflect the average retinal arteriole (central retinal arteriole equivalent [CRAE]) and venule (central retinal venule equivalent [CRVE]) diameter of an eye, respectively.

Results  While controlling for age, study site, glycosylated hemoglobin level, and ambulatory pulse rate, the daytime ambulatory systolic (–0.29-µm effect per 1 mm Hg; P = .02), daytime ambulatory diastolic (–0.44-µm effect per 1 mm Hg; P = .04), nighttime ambulatory systolic (–0.27-µm effect per 1 mm Hg; P = .03), and 24-hour ambulatory systolic (–0.31-µm effect per 1 mm Hg; P = .03) BPs were cross-sectionally associated with a smaller CRAE. While controlling for age, study site, glycosylated hemoglobin level, ambulatory pulse rate, and baseline CRAE, no BP measure was associated with a change in CRAE or CRVE during 5 years of follow-up. Treatment with losartan potassium or enalapril maleate was not associated with a statistically significant change in CRAE or CRVE.

Conclusion  Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy does not affect retinal arteriole or venule diameter in normotensive persons with type 1 diabetes mellitus.

Trial Registration  clinicaltrials.gov Identifier: NCT00143949

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Impact of Liver Transplantation on Transthyretin-Related Ocular Amyloidosis in Japanese Patients [Clinical Sciences]

Objective  To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients.

Methods  Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities—the most common ocular manifestation of FAP—in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis.

Results  Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not.

Conclusions  Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.

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Development of Choroidal Neovascularization in Rats With Advanced Intense Cyclic Light-Induced Retinal Degeneration [Laboratory Sciences]

Objectives  To study the progressive changes of intense cyclic light–induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV).

Methods  Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal– and nitrotyrosine-modified proteins by immunofluorescence staining.

Results  Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light–exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels.

Conclusions  Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration.

Clinical Relevance  The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

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Expression of Vascular Endothelial Growth Factor in Retinoblastoma [Laboratory Sciences]

Objectives  To investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) and to determine its possible association with tumor differentiation status, optic nerve and/or choroidal invasion, anterior chamber invasion, vitreous seeding, and basophilic staining of the vascular walls.

Methods  A retrospective study was performed to identify the expression of VEGF in 47 of 129 consecutive patients with retinoblastoma treated at the Ocular Pathology Laboratory of the Anatomy and Pathology Institute of the Central University of Venezuela in Caracas from January 1, 2000, through December 31, 2007.

Results  A positive correlation between VEGF staining intensity and time of progression and mitotic and apoptotic indexes was observed. However, no correlation was found between VEGF expression and other prognostic factors in this malignant neoplasm, including tumor stage as assessed by the Grabowski and Abramson classification.

Conclusions  Although the isolated characterization of VEGF in retinoblastoma is not grounds for this protein to be considered a prognostic factor, its association with mitotic and apoptotic indexes suggests it may play a role in the progression of this disease. Thus, therapeutic targeting of VEGF in retinoblastoma may be an effective strategy to reduce tumor progression.

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Rate of Endophthalmitis After Cataract Surgery in Quebec, Canada, 1996-2005 [Epidemiology]

Objective  To estimate the annual incidence of endophthalmitis after cataract surgery from January 1, 1996, through December 31, 2005, in Quebec, Canada.

Methods  Deidentified data were obtained from an outpatient physician billing database (Quebec State Control for Health Insurance [RAMQ]) with regard to all cataract surgical procedures performed from January 1, 1996, through December 31, 2005, in Quebec. For this cohort, records of an International Classification of Diseases, Ninth Revision (ICD-9) code for endophthalmitis during the same years were requested from 2 sources: the RAMQ outpatient database and an inpatient hospital discharge database (Maintenance and Exploitation of Data for the Study of Hospitalized Patients [MED-ECHO]). Endophthalmitis after cataract surgery was assumed if it occurred within 90 days of the surgery. Risk factors were examined using ² tests and logistic regression.

Results  After exclusions, 490 690 cataract surgical procedures were performed from January 1, 1996, through December 31, 2005. A total of 754 cases of endophthalmitis occurred within 90 days after surgery for an overall incidence rate of 1.5 per 1000 surgical procedures (95% confidence interval [CI], 1.4-1.7). Factors associated with endophthalmitis included age of 85 years or older (odds ratio [OR], 1.34; 95% CI, 1.06-1.70), male sex (1.44; 1.24-1.66), later year of surgery (0.94; 0.92-0.97), and region of cataract surgery, because regions 6 (2.21; 1.91-2.55) and 9 (4.00; 2.48-6.43) had higher rates compared with all other regions.

Conclusion  Reasons that explain the apparent decrease in endophthalmitis, especially in 2005, should be explored and further research performed to understand why certain patients and regions have higher risks of endophthalmitis after cataract surgery.

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Association Between the Use of Glaucoma Medications and Mortality [Socioeconomics and Health Services]

Objective  To evaluate the relationship between glaucoma medication use and death.

Methods  This study uses longitudinal data from 2003 to 2007 on persons 40 years and older with glaucoma or suspected glaucoma enrolled in a large managed care network. Cox regression analysis was performed to estimate the hazard of death associated with the use of various glaucoma medication classes and combinations thereof. Multivariable models were adjusted for demographic characteristics and comorbid medical conditions.

Results  Of 21 506 participants with glaucoma or suspected glaucoma, 237 (1.1%) died during the study period. The use of any class of glaucoma medication was associated with a 74% reduced hazard of death (adjusted hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.16-0.40) compared with no glaucoma medication use. This association was observed for use of a single agent alone, such as a topical β-antagonist (0.44; 0.24-0.83) or a prostaglandin analogue (0.31; 0.18-0.54), and for use of different combinations of drug classes.

Conclusions  After adjustment for potential confounding variables, the use of glaucoma medications was associated with a reduced likelihood of death in this large sample of US adults with glaucoma. Future investigations should explore this association further because these findings may have important clinical implications.

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Harvesting Fresh Tumor Tissue From Enucleated Eyes: The 2008 Jack S. Guyton Lecture [Surgical Technique]

There is an increasing need to obtain fresh tumor tissue and normal tissue for genetic studies and research following enucleation of an eye for uveal melanoma, retinoblastoma, and other lesions. A concern about doing this is that the globe will often collapse and lead to difficulties with gross and histopathologic interpretation. The technique reported herein is based on the creation of an opening in the sclera using an 8-mm corneal trephine followed by removal of tumor tissue. This method provides adequate tissue, preserves the spherical configuration of the eye, and allows for excellent histopathologic sections.

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Intense Cyclic Light-Induced Retinal Degeneration in Rats [Editorial]

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Moving Toward Information in the Blink of an Eye [Editorial]

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Kindred With Prominent Corneal Nerves Associated With a Mutation in Codon 804 of RET on Chromosome 10q11 [Small Case Series]

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Intravitreous Ranibizumab (Lucentis) for Radiation Maculopathy [Small Case Series]

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September 2009 Archives Web Quiz Winner [Archives Web Quiz Winner]

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Unusual Adaptive Optics Findings in a Patient With Bilateral Maculopathy [Research Letters]

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Topical Treatment for Capillary Hemangioma of the Eyelid Using {beta}-Blocker Solution [Research Letters]

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Propranolol for Isolated Orbital Infantile Hemangioma [Research Letters]

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Ocular Involvement by Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly: A New Disease Entity in the World Health Organization Classification [Research Letters]

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Severe Retinal Vascular Infarction After Photodynamic Therapy With Verteporfin Using the Standard Protocol [Research Letters]

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Diabetic Macular Edema Following Panretinal Photocoagulation [Letters]

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Diabetic Macular Edema Following Panretinal Photocoagulation--Reply [Letters]

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Reviewers Who Completed a Review During 2009 [Annual Reviewers List]

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About This Journal [About This Journal]

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Randomized Trial of Effect of Bifocal and Prismatic Bifocal Spectacles on Myopic Progression: Two-Year Results [Clinical Trial]

Objective  To determine whether bifocal and prismatic bifocal spectacles could control myopia in children with high rates of myopic progression.

Methods  This was a randomized controlled clinical trial. One hundred thirty-five (73 girls and 62 boys) myopic Chinese Canadian children (myopia of ≥1.00 diopters [D]) with myopic progression of at least 0.50 D in the preceding year were randomly assigned to 1 of 3 treatments: (1) single-vision lenses (n = 41), (2) +1.50-D executive bifocals (n = 48), or (3) +1.50-D executive bifocals with a 3–prism diopters base-in prism in the near segment of each lens (n = 46).

Main Outcome Measures  Myopic progression measured by an automated refractor under cycloplegia and increase in axial length (secondary) measured by ultrasonography at 6-month intervals for 24 months. Only the data of the right eye were used.

Results  Of the 135 children (mean age, 10.29 years [SE, 0.15 years]; mean visual acuity, –3.08 D [SE, 0.10 D]), 131 (97%) completed the trial after 24 months. Myopic progression averaged –1.55 D (SE, 0.12 D) for those who wore single-vision lenses, –0.96 D (SE, 0.09 D) for those who wore bifocals, and –0.70 D (SE, 0.10 D) for those who wore prismatic bifocals. Axial length increased an average of 0.62 mm (SE, 0.04 mm), 0.41 mm (SE, 0.04 mm), and 0.41 mm (SE, 0.05 mm), respectively. The treatment effect of bifocals (0.59 D) and prismatic bifocals (0.85 D) was significant (P < .001) and both bifocal groups had less axial elongation (0.21 mm) than the single-vision lens group (P < .001).

Conclusions  Bifocal lenses can moderately slow myopic progression in children with high rates of progression after 24 months.

Applications to Clinical Practice  Bifocal spectacles may be considered for slowing myopic progression in children with an annual progression rate of at least 0.50 D.

Trial Registration  clinicaltrials.gov Identifier: NCT00787579

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The Infant Aphakia Treatment Study: Design and Clinical Measures at Enrollment [Clinical Trial]

Objective  To compare the use of contact lenses and intraocular lenses (IOLs) for the optical correction of unilateral aphakia during infancy.

Methods  In a randomized, multicenter (12 sites) clinical trial, 114 infants with unilateral congenital cataracts were assigned to undergo cataract surgery with or without IOL implantation. Children randomized to IOL treatment had their residual refractive error corrected with spectacles. Children randomized to no IOL treatment had their aphakia treated with a contact lens.

Main Outcome Measures  Grating acuity at 12 months of age and HOTV visual acuity at 41/2 years of age.

Application to Clinical Practice  This study should determine whether either treatment for an infant with a visually significant unilateral congenital cataract results in a better visual outcome.

Results  Enrollment began December 23, 2004, and was completed January 16, 2009. The median age at the time of cataract surgery was 1.8 months. Fifty patients were 4 to 6 weeks of age at the time of enrollment; 32, 7 weeks to 3 months of age; and the remaining 32, more than 3 to less than 7 months of age. Fifty-seven children were randomized to each treatment group. Eyes with cataracts had shorter axial lengths and steeper corneas on average than the fellow eyes.

Conclusions  The optimal optical treatment of aphakia in infants is unknown. However, the Infant Aphakia Treatment Study was designed to provide empirical evidence of whether optical treatment with an IOL or a contact lens after unilateral cataract surgery during infancy is associated with a better visual outcome.

Trial Registration  clinicaltrials.gov Identifier: NCT00212134

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Outbreak of Acquired Ocular Toxoplasmosis Involving 248 Patients [Clinical Sciences]

Objective  To describe the demographic profile and clinical and laboratory findings of 248 patients with acquired retinitis caused by systemic infection with toxoplasmosis in a presumed outbreak of the disease.

Design  Retrospective observational case series.

Results  Most patients (209) were residents of one city in Southern India. A total of 35 patients had a prodrome of fever, and 242 patients had unilateral retinitis without associated old retinochoroidal scars. All had laboratory evidence of acquired systemic infection with Toxoplasma gondii, and all favorably responded to antitoxoplasma therapy. Toxoplasma IgM and IgG antibodies were detected, suggesting recently acquired systemic disease. Complications seen were macular scars in 50 eyes (25.1%); epiretinal membranes, 23 eyes (11.5%); cataract, 5 eyes (2.5%); posterior vitreous detachment, 12 eyes (6%); and retinal detachment, 12 eyes (6%). One recurrence has been seen. The suspected source of infection is municipal drinking water.

Conclusion  Large numbers of residents of any age in a population are at risk of acquiring ocular disease during an outbreak of toxoplasmosis, which can go unnoticed, and can cause significant ocular morbidity.

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High Caloric and Sodium Intakes as Risk Factors for Progression of Retinopathy in Type 1 Diabetes Mellitus [Clinical Sciences]

Objective  To report the association of dietary nutrient intakes in relation to the 6-year progression of diabetic retinopathy (DR) in African American patients with type 1 diabetes mellitus.

Methods  African American patients with type 1 diabetes who participated in the baseline and 6-year follow-up examinations as part of the New Jersey 725 study were included. At the baseline examination, a food frequency questionnaire was used to document average daily dietary nutrient intakes. Clinical evaluations at baseline and at the 6-year follow-up also included a structured clinical interview, ocular examination, grading of 7 standard field stereoscopic fundus photographs, and blood pressure measurements. Biological evaluations included blood and urine assays. Nutrient intake data were analyzed using DietSys software and nutrient databases developed by the National Cancer Institute.

Results  Among the 469 participants at risk for progression of DR, baseline total caloric intake was significantly associated with 6-year incidence of vision-threatening DR (either proliferative DR or macular edema) and of severe hard exudates—after adjusting for clinical risk factors for DR progression. Baseline high sodium intake was a significant and independent risk factor for 6-year incidence of macular edema.

Conclusions  In African American patients with type 1 diabetes, high caloric and sodium intakes are significant and independent risk factors for progression to severe forms of DR. Dietary recommendations of low caloric and sodium intakes may be beneficial in relation to the development of DR.

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Prevalence and Risk Factors of Retinopathy in an Asian Population Without Diabetes: The Singapore Malay Eye Study [Clinical Sciences]

Objective  To describe the prevalence and risk factors of retinopathy in an Asian population without diabetes.

Methods  We conducted a population-based, cross-sectional study of 3280 Malays aged 40 to 80 years residing in Singapore. Participants had retinal photographs taken, which were graded for retinopathy signs using the modified Airlie House Classification System. Risk factors were assessed from standardized interviews, clinical examinations, and laboratory investigations.

Results  Of participants without diabetes (n = 2500), 149 (6.0%; 95% confidence interval [CI], 5.0-6.9) had signs of retinopathy that represented minimal (5.8%) or mild (0.2%) retinopathy. After adjusting for multiple covariables, higher serum glucose levels (odds ratio [OR], 1.13; 95% CI, 1.00-1.28; per millimole per liter increase), higher systolic blood pressure (OR, 1.15; 95% CI, 1.06-1.25; per 10–mm Hg increase), higher body mass index (OR, 1.04; 95% CI, 1.00-1.07 per point increase), and a history of heart attack (OR, 2.68; 95% CI, 1.48-4.83) were significantly associated with the presence of retinopathy lesions in persons without diabetes.

Conclusions  Similar to studies in white individuals, signs of retinopathy are common in Asian persons without diabetes. Early signs of retinopathy in persons without diabetes are related to metabolic and vascular risk factors and may indicate intermediate pathologic changes along the pathway to cardiovascular disease.

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Fundus Autofluorescence Imaging of the White Dot Syndromes [Clinical Sciences]

Objective  To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs).

Methods  Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence.

Results  Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P < .001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P < .001).

Conclusions  Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs.

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Retinoschisis Detected With Handheld Spectral-Domain Optical Coherence Tomography in Neonates With Advanced Retinopathy of Prematurity [Clinical Sciences]

Objectives  The recent development of handheld spectral-domain optical coherence tomography (HHSD-OCT) has enabled us to obtain high-resolution retinal scans of premature infants with retinopathy of prematurity (ROP). The purpose of this study is to document HHSD-OCT findings in laser-treated neonates with progressive ROP.

Methods  This is a retrospective consecutive case series of 3 patients with progressive ROP despite laser photocoagulation. All patients were transferred from peripheral neonatal intensive care units (NICUs) to the Children's Hospital Los Angeles. All patients had a complete ocular examination, fundus photography, fluorescein angiography, and HHSD-OCT.

Results  All 3 patients had active progressive ROP despite prior laser photocoagulation. Of the 6 eyes, 1 was excluded from the study because it had an exudative retinal detachment following laser photocoagulation. Retinal detachment was not detected on clinical examination in the 5 remaining eyes, although there was vitreoretinal traction at the ridges of 3 of the 5 eyes. The HHSD-OCT identified presumed retinoschisis in all 5 study eyes.

Conclusions  Tractional retinoschisis may be an important finding in progressive laser-treated ROP, made possible by use of the HHSD-OCT. This finding may have significant implications for how we classify and treat patients whose ROP is progressing despite laser treatment. Furthermore, the use of the HHSD-OCT can provide valuable insight into the interaction of the retina, vitreous, and ridge in patients with progressive ROP, and it allows shallow detachments and retinoschisis to be diagnosed earlier and more accurately than would otherwise be possible.

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Dr Thompson's Eye Water [Ophthalmological Ephemera]

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Endothelial Cell Density to Predict Endothelial Graft Failure After Penetrating Keratoplasty [Clinical Sciences]

Objective  To determine whether preoperative and/or postoperative central endothelial cell density (ECD) and its rate of decline postoperatively are predictive of graft failure caused by endothelial decompensation following penetrating keratoplasty to treat a moderate-risk condition, principally, Fuchs dystrophy or pseudophakic corneal edema.

Methods  In a subset of Cornea Donor Study participants, a central reading center determined preoperative and postoperative ECD from available specular images for 17 grafts that failed because of endothelial decompensation and 483 grafts that did not fail.

Results  Preoperative ECD was not predictive of graft failure caused by endothelial decompensation (P = .91). However, the 6-month ECD was predictive of subsequent failure (P < .001). Among those that had not failed within the first 6 months, the 5-year cumulative incidence (±95% confidence interval) of failure was 13% (±12%) for the 33 participants with a 6-month ECD of less than 1700 cells/mm² vs 2% (±3%) for the 137 participants with a 6-month ECD of 2500 cells/mm² or higher. After 5 years' follow-up, 40 of 277 participants (14%) with a clear graft had an ECD below 500 cells/mm².

Conclusions  Preoperative ECD is unrelated to graft failure from endothelial decompensation, whereas there is a strong correlation of ECD at 6 months with graft failure from endothelial decompensation. A graft can remain clear after 5 years even when the ECD is below 500 cells/mm².

Clinical Trial Registry  clinicaltrials.gov Identifier: NCT00006411

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Recognition Acuity, Grating Acuity, Contrast Sensitivity, and Visual Fields in 6-Year-Old Children [Clinical Sciences]

Objective  To measure monocular distance visual acuity (VA), grating VA, contrast sensitivity, and visual field extent in full-term, 6-year-old children.

Methods  Subjects were 59 healthy full-term children aged 5.8 to 6.3 years who had no ocular abnormalities and no myopia of 1.00 diopter (D) or greater, hyperopia of 4.00 D or greater, astigmatism of 1.50 D or greater, or anisometropia of 1.50 D or greater spherical equivalent or cylinder, as evaluated by a standard eye examination with cycloplegic refraction. All were tested monocularly for recognition acuity (Early Treatment Diabetic Retinopathy Study VA charts), grating acuity (Teller acuity cards), contrast sensitivity (Pelli-Robson contrast sensitivity charts), and visual field extent (white-sphere kinetic perimetry).

Results  Right and left eye values did not differ significantly. Mean values for the right eye were 0.040 logMAR (SD, 0.075 log units) for Early Treatment Diabetic Retinopathy Study VA, 24.5 cycles per degree (SD, 0.3 octaves) for grating acuity, and 1.63 (SD, 0.12 log units) for contrast sensitivity. Mean visual field extent for the inferonasal, superonasal, superotemporal, and inferotemporal meridians was 59.1° (SD, 9.7°), 57.8° (SD, 9.6°), 71.2° (SD, 12.3°), and 100.4° (SD, 6.6°), respectively.

Conclusions  The results provide additional normative monocular data on visual function in 6-year-old children and indicate that their thresholds are less than those of adults for distance recognition VA, grating VA, and contrast sensitivity, but similar to those of adults for white-sphere kinetic perimetry.

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Confocal Microscopy of Corneal Wound Healing After Deep Lamellar Keratoplasty in Rabbits [Laboratory Sciences]

Objective  To compare wound healing and morphologic characteristics of the host-donor interface in rabbit corneas after maximum-depth and near–Descemet membrane anterior lamellar keratoplasty.

Design  Descriptive analysis of confocal microscopy images after 2 types of deep lamellar keratoplasty (deep stromal dissection vs total stromal resection).

Methods  Deep anterior lamellar keratoplasty (DALK) was performed in 16 rabbit eyes, with exposure of the Descemet membrane in 8 eyes (deep group) and deep stromal dissection to near the Descemet membrane in 8 eyes (near group). A full-thickness graft devoid of endothelium and Descemet membrane was sutured in place. Confocal examination of lamellar interface and wound edge was performed throughout 6 months.

Results  Four days postoperatively, confocal microscopy revealed numerous highly reflective keratocytes at and adjacent to the interface in all eyes, fewer in the deep than the near group. Keratocyte density and reflectivity returned to normal at 4 to 6 weeks (deep) and 8 to 10 weeks (near) postoperatively.

Conclusions  In the deep group, the smooth interface showed less scarring. In the near group, stroma-to-stroma healing stimulated more activated keratocytes and hence more haze. Successful DALK requires minimal central healing for clarity but significant suture-stimulated healing at the edge to prevent corneal bulge.

Clinical Relevance  Deep anterior lamellar keratoplasty is rarely accompanied by rejection, avoids entrance into the anterior chamber, and can be performed with tissue that does not have living keratocytes. Interface healing is a determinant of the final visual acuity; depth of the lamellar bed is a major determinant of the healing response. Although dissection to bare the Descemet membrane is more difficult, there is less keratocyte activation and scarring.

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Subconjunctival Delivery of Antibiotics in a Controlled-Release System: A Novel Anti-infective Prophylaxis Approach for Cataract Surgery [Laboratory Sciences]

Objective  To compare the efficacy of subconjunctival injection of a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL, in a controlled-release system (DuoCat) with that of ciprofloxacin hydrochloride, 0.3%, eyedrops for infection prophylaxis.

Methods  Rabbit eyes were injected subconjunctivally with a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL, or ciprofloxacin hydrochloride, 2 mg/0.1 mL, alone. The aqueous and vitreous humor pharmacokinetic profiles were compared with those of a single drop of ciprofloxacin hydrochloride, 0.3%, 6 times daily. In 45 rabbits, Staphylococcus aureus was injected into the anterior chamber: 15 randomly received 1 drop of ciprofloxacin hydrochloride, 0.3%, every 4 hours during 24 hours; 15 received drops of balanced salt solution; and 15 received a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL. After 24 hours, endophthalmitis scores were recorded, aqueous and vitreous humors underwent culture, and histologic analysis was performed.

Results  The combined triamcinolone and ciprofloxacin treatment allowed higher intraocular levels of ciprofloxacin. The median endophthalmitis clinical scores for the combination of triamcinolone and ciprofloxacin and ciprofloxacin-only eyedrop groups were equivalent (P = .42) and were significantly lower than those of the balanced salt solution group (P < .001). The culture was negative for S aureus in the combined triamcinolone and ciprofloxacin and ciprofloxacin eyedrop regimens. No adverse effects were observed with either route.

Conclusions  Ciprofloxacin eyedrops and combined triamcinolone and ciprofloxacin were equally tolerated and efficacious. The combined triamcinolone and ciprofloxacin treatment may eliminate noncompliance issues and may prove to be a valuable clinical tool for surgical prophylaxis.

Clinical Relevance  The combined triamcinolone and ciprofloxacin treatment may be a new useful strategy for surgical prophylaxis.

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Measuring Refraction in Adults in Epidemiological Studies [Epidemiology]

Objective  To compare refraction measured before and after pharmacologic cycloplegia.

Methods  This study used preliminary data from the Beaver Dam Offspring Study, which includes adult children of participants in the population-based Epidemiology of Hearing Loss Study of older adults living in Beaver Dam, Wisconsin. Data were available for 5018 eyes of 2529 participants. Refraction was defined by the spherical equivalent (SE), using autorefractor readings. Differences were calculated as the SE after drops were administered minus the SE before drops were administered. Myopia was defined as SE of –1 diopter (D) or less; emmetropia, as SE more than –1 D and less than 1 D; and hyperopia, as SE of 1 D or more.

Results  The mean age was 48 years (range, 22-84 years). The mean difference in SE between measurements before and after cycloplegia was 0.29 D (95% confidence interval, 0.28-0.31). The difference decreased with age and varied by refractive status for participants younger than 50 years, with the largest differences observed among young persons with hyperopic refractive errors. Across all age groups, agreement on classifications of refraction was high (84%-92%).

Conclusions  Overall, clinically inconsequential differences were observed between SEs before and after pharmacologic cycloplegia, suggesting that cycloplegia may not be necessary in epidemiological studies of refraction in adults.

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Minimal Clinically Important Difference for the Ocular Surface Disease Index [Socioeconomics and Health Services]

Objective  To assess the minimal clinically important difference (MCID) for the Ocular Surface Disease Index (OSDI; Allergan Inc, Irvine, California, holds the copyright), a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to dry eye disease.

Methods  Study data were collected within the Restasis Review of Efficacy and Safety vs Tears in the Relief of Dry Eye (RESTORE), an observational registry. A clinician global impression (CGI) and a subject global assessment (SGA) served as anchors to estimate the MCID for the overall OSDI score (range, 0-100). The overall OSDI score defined the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease. RESTORE patients were included if they completed the OSDI at the baseline visit and at a follow-up visit and had a global change rating (SGA or CGI).

Results  Three hundred ten patients were included (82.3% white and 81.6% female [mean age, 57.8 years]). The CGI and SGA correlated with the OSDI score change for all OSDI categories except the normal category. The MCID ranged from 7.0 to 9.9 for all OSDI categories. The MCID ranged from 4.5 to 7.3 for mild or moderate disease and from 7.3 to 13.4 for severe disease.

Conclusions  Using observational data, we estimated the MCIDs for different baseline OSDI categories of dry eye disease. These results will assist clinicians and researchers when interpreting OSDI score changes.

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Association Between Erythropoietin Gene Polymorphisms and Diabetic Retinopathy [Ophthalmic Molecular Genetics]

Objective  To determine whether sequence variation in the erythropoietin gene (EPO) is associated with the development of diabetic retinopathy (DR).

Methods  This was a multicenter study based on 518 subjects with long-standing diabetes mellitus (DM), 173 with type 1 DM (T1DM) and 345 with type 2 DM (T2DM). Study groups consisted of 233 control subjects with no DR, 155 subjects with nonproliferative DR, 126 with proliferative DR, and 90 with clinically significant macular edema. Subjects with end-stage renal disease were excluded. DNA extracted from blood of each subject was genotyped for 3 EPO single-nucleotide polymorphisms (SNPs).

Results  All 3 SNPs in EPO were associated with overall DR status in the combined T1DM and T2DM and T2DM alone groups (CC genotype of rs507392, P < .008; GG genotype of rs1617640, P < .008; and CC genotype of rs551238, P < .008) in the multivariate analysis. The GCC haplotype was also associated with overall DR status in the combined DM and T2DM alone groups (P = .008) by multivariate analysis. All SNPs and the GCC haplotype were also associated with proliferative DR and clinically significant macular edema in the combined DM and T2DM alone groups. No associations were found with T1DM alone.

Conclusion  Sequence variation in EPO is associated with the risk of DR independent of duration of DM, degree of glycemic control, and nephropathy.

Clinical Relevance  Identifying EPO genetic markers for high risk of developing DR could lead to the possibility of developing novel treatments or preventive therapies.

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Genotype-Phenotype Correlation for Leber Congenital Amaurosis in Northern Pakistan [Ophthalmic Molecular Genetics]

Objectives  To report the genetic basis of Leber congenital amaurosis (LCA) in northern Pakistan and to describe the phenotype.

Methods  DNA from 14 families was analyzed using single-nucleotide polymorphism and microsatellite genotyping and direct sequencing to determine the genes and mutations involved. The history and examination findings from 64 affected individuals were analyzed to show genotype-phenotype correlation and phenotypic progression.

Results  Homozygous mutations were found in RPGRIP1 (4 families), AIPL1 and LCA5 (3 families each), and RPE65, CRB1, and TULP1 (1 family each). Six of the mutations are novel. An additional family demonstrated linkage to the LCA9 locus. Visual acuity, severe keratoconus, cataract, and macular atrophy were the most helpful features in predicting the genotype. Many of the phenotypic variables became more prevalent with increasing age.

Conclusions  Leber congenital amaurosis in northern Pakistan is genetically heterogeneous. Mutations in RPGRIP1, AIPL1, and LCA5 accounted for disease in 10 of the 14 families. This study illustrates the differences in phenotype, for both the anterior and posterior segments, seen between patients with identical or different mutations in the LCA genes and also suggests that at least some of the phenotypic variation is age dependent.

Clinical Relevance  The LCA phenotype, especially one including different generations in the same family, may be used to refine a molecular diagnostic strategy.

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August 2009 Archives Web Quiz Winner [Archives Web Quiz Winner]

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Use of a Microvascular Clip for Iris Fixation of an Intraocular Lens: A Laboratory Model [Surgical Technique]

Here we present a potential novel surgical technique consisting of fixation of a posterior-chamber intraocular lens to the iris that may be used in the treatment of aphakia or the management of intraocular lens complications when capsular support has been compromised. The technique was performed in a laboratory model using cadaveric human eyes. A commercially available neurovascular clip was used to securely fasten the intraocular lens to the iris with minimal trauma. The use of a metal clip has the advantage of avoiding potential risks of suture fixation such as suture breakage. Also, this technique is easier than suturing and may potentially serve as another tool in a cornea surgeon's armamentarium.

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Simulating Vision With and Without Macular Disease [Special Article]

Conventional photographs do not show how, at any moment of visual fixation, neural vision is clear only in the foveal center. We have developed new computer simulations to show both normal vision and vision with macular disease. These simulations show the nature of momentary vision for life tasks such as reading, facial recognition, and walking in the street. They also dramatically show the impact of macular disease (with scotomas and visual distortion), as there is no surrounding region of clarity. We hope these images will be instructive to both physicians and patients.

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Colorful Visual Experiences During Cataract Surgery [Ophthalmic Images]

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An Epidemic of Toxoplasmosis: Lessons From Coimbatore, India [Editorial]

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Informing Patient Choice and Consent: What Patients Really Want and Need to Know [Editorial]

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Idiopathic Orbital Inflammation and Graves Ophthalmopathy [Small Case Series]

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Delayed Diagnosis of Microcystic Adnexal Carcinoma in Progressive Eyelid Distortion [Small Case Series]

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Cost Analysis of Povidone-Iodine for Ophthalmia Neonatorum Prophylaxis [Research Letters]

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Shifting Distribution of Chicago-Area Acanthamoeba Keratitis Cases [Research Letters]

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Marked Cup Reversal Presumably Associated With Scleral Biomechanics in a Case of Adult Glaucoma [Research Letters]

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Characterization of Retinal Nerve Fiber Layer in Nonglaucomatous Eyes With Tilted Discs [Research Letters]

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Intraretinal Neovascularization in Diabetic Retinopathy [Research Letters]

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Glomus Cell Tumor of the Orbit [Research Letters]

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Association of Proliferative Diabetic Retinopathy With Insulin Use and Microalbuminuria [Letters]

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Association of Proliferative Diabetic Retinopathy With Insulin Use and Microalbuminuria--Reply [Letters]

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Controversies of Diagnosing Autoimmune Retinopathy [Letters]

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Controversies of Diagnosing Autoimmune Retinopathy--Reply [Letters]

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About This Journal [About This Journal]

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Exploratory Analysis of Diabetic Retinopathy Progression Through 3 Years in a Randomized Clinical Trial That Compares Intravitreal Triamcinolone Acetonide With Focal/Grid Photocoagulation [Clinical Sciences]

Objective  To compare the effect of intravitreal triamcinolone acetonide with focal/grid photocoagulation on the progression of diabetic retinopathy.

Methods  We performed an exploratory analysis of participants with diabetic macular edema randomly assigned to receive laser therapy or intravitreal triamcinolone acetonide (1 or 4 mg). Fundus photographs were obtained at baseline and 1, 2, and 3 years. The main outcome measure was progression to proliferative diabetic retinopathy or worsening of 2 or more severity levels on reading-center masked assessment of 7-field fundus photographs, plus additional eyes that received panretinal photocoagulation or had a vitreous hemorrhage.

Results  From July 15, 2004, through May 5, 2006, 840 eyes from 693 participants were enrolled in the study and randomly assigned to receive laser therapy (n = 330), 1 mg of triamcinolone acetonide (n = 256), or 4 mg of triamcinolone acetonide (n = 254). The cumulative probability of progression of retinopathy at 2 years was 31% (laser group), 29% (1-mg group), and 21% (4-mg group) (P = .64 in the 1-mg group and .005 in the 4-mg group compared with the laser group). These differences appeared to be sustained at 3 years.

Conclusions  Intravitreal triamcinolone acetonide (4 mg) appeared to reduce the risk of progression of diabetic retinopathy. Given the exploratory nature of this analysis and because intravitreal triamcinolone adverse effects include cataract formation and glaucoma, use of this treatment merely to reduce the rates of progression of proliferative diabetic retinopathy or worsening of the level of diabetic retinopathy does not seem warranted at this time.

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Melanoma-Associated Retinopathy: A Paraneoplastic Autoimmune Complication [Clinical Sciences]

Objectives  To study 11 patients with melanoma-associated retinopathy (MAR) to clarify the reliability of various methods of diagnostic testing, to determine the underlying antigenic retinal proteins, and to study the clinical histories and types of associated melanomas.

Methods  Clinical data were obtained from patients with melanoma who developed marked visual problems. Testing included electroretinography, kinetic visual fields, comparative studies of Western blots, and indirect immunohistologic examination to detect antiretinal antibodies, as well as proteomic studies to identify underlying antigenic retinal proteins.

Results  Patients with MAR typically have rapid onset of photopsias, scotomata, and loss of central or paracentral vision. Ophthalmoscopy seldom shows significant changes early, but electroretinograms are abnormal. Results of Western blots and immunohistologic examination can show antiretinal antibodies but not always. Most patients (9 of 11) had a strong family history of autoimmune disorders. Any type of melanoma (cutaneous, choroidal, ciliary body, or choroidal nevi) may be associated with this paraneoplastic autoimmune reactivity. MAR may precede or follow the diagnosis of melanoma. Patients with MAR have the same antigenic retinal proteins that have been associated with cancer-associated retinopathy. In addition, 2 new antigenic retinal proteins, aldolase A and aldolase C, were found.

Conclusions  There was a high prevalence of positive family histories of autoimmune disease in patients with MAR. To confirm the disorder, multiple clinical and serum diagnostic techniques (Western blot or indirect immunohistologic examination) are needed. Two newly observed antigenic retinal proteins, aldolase A and aldolase C, are associated with MAR.

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Risk of Endophthalmitis After Intravitreal Drug Injection When Topical Antibiotics Are Not Required: The Diabetic Retinopathy Clinical Research Network Laser-Ranibizumab-Triamcinolone Clinical Trials [Clinical Sciences]

Objective  To report the incidence of endophthalmitis after intravitreal drug injection by means of a standardized procedure that does not require topical antibiotics, sterile gloves, or a sterile drape.

Methods  Intravitreal injections of preservative-free triamcinolone acetonide or ranibizumab were administered in 2 prospective randomized clinical trials performed by the Diabetic Retinopathy Clinical Research Network. The standardized procedure for these trials requires the use of a topical combination product of povidone-iodine, a sterile lid speculum, and topical anesthetic, but does not require the use of topical antibiotics before, on the day of, or after injection.

Results  As of February 23, 2009, a total of 3226 intravitreal injections of ranibizumab and 612 injections of preservative-free triamcinolone had been administered. Topical antibiotics were given on the day of injection in 361 (9.4%) of the 3838 cases, for several days after injection in 813 cases (21.2%), on the day of injection and after injection in 1388 cases (36.2%), and neither on the day of injection nor after injection in 1276 cases (33.3%). Three cases of culture-positive endophthalmitis occurred after ranibizumab injections (0.09%), and no cases occurred after triamcinolone injections. In all 3 cases of endophthalmitis, topical antibiotics were given for several days after the injection but not before injection.

Conclusions  The results suggest that a low rate of endophthalmitis can be achieved by means of a protocol that includes use of topical povidone-iodine, a sterile lid speculum, and topical anesthetic, but does not require topical antibiotics, sterile gloves, or a sterile drape.

Trial Registration  clinicaltrials.gov Identifiers: NCT00444600 and NCT00445003

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Short Tag Noose Technique for Optional and Late Suture Adjustment in Strabismus Surgery [Clinical Sciences]

Objective  To present and evaluate a new technique that allows the second-stage suture adjustment in strabismus surgery to be skipped or delayed if the immediate postoperative alignment is satisfactory.

Methods  The "short tag noose" technique replaces long sutures with short tags that can be left under the conjunctiva after adjustment. Retrospectively, the medical records of all patients treated by a single surgeon with this approach between January 1, 2005, and December 31, 2008, were evaluated for success rate (≤10 prism diopters [PD] horizontal and ≤6 PD vertical), reoperation rate, and complications.

Results  Of 120 procedures reviewed, 27 (22.5%) were performed in children; 97 procedures (80.8%) were performed in patients with complex strabismus. Mean follow-up was 6 months. The success rate was 81.0% for horizontal strabismus and 70.7% for vertical strabismus at 2 months. The reoperation rate was 10.0% for horizontal strabismus and 19.0% for vertical strabismus. The noose slipped in 1 patient (0.8%) and was corrected by readjustment on day 4. Two patients (1.7%) required in-office excision of cysts or granulomas.

Conclusions  The short tag noose technique simplifies the logistics of suture adjustment and avoids the need for sedation in children who do not require adjustment. It provides the ability to defer adjustment for days after surgery.

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Dr Thompson's Eye Water [Ophthalmological Ephemera]

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Comparison Between the plusoptiX and MTI Photoscreeners [Clinical Sciences]

Objective  Both the Medical Technology and Innovations (MTI) and plusoptiX photoscreeners are used to objectively screen for amblyogenic risk factors in children. The MTI has been extensively studied, but the limited availability of film may render it obsolete. We compared the MTI with the plusoptiX, a newer digital photoscreener, for the ability to detect amblyogenic factors when compared with a comprehensive pediatric ophthalmic examination. We believe our results will help to guide community-based vision screening programs.

Methods  One hundred fifty-one children were examined consecutively in our office. Each patient was screened with the MTI and plusoptiX devices on the same day as part of a comprehensive pediatric ophthalmic examination. Results via MTI were evaluated by an expert masked examiner (R.W.A.), and the plusoptiX results were interpreted by the incorporated software.

Results  Sixty-five percent of patients were found to have amblyopia or amblyogenic risk factors during the pediatric ophthalmic examination conducted via the American Association of Pediatric Ophthalmology and Strabismus referral criteria. We found the MTI photoscreener to have a sensitivity of 83.6%, specificity of 90.5%, false- positive rate of 9.4%, false-negative rate of 16.3%, and positive predictive value of 94.2%. The plusoptiX demonstrated a sensitivity of 98.9%, specificity of 96.1%, false- positive rate of 3.7%, false-negative rate of 1.0%, and positive predictive value of 97.9%.

Conclusion  The MTI and plusoptiX photoscreeners proved to be effective when compared with a comprehensive cycloplegic pediatric ophthalmic examination. The plusoptiX, however, was found to have a higher sensitivity and specificity than the MTI.

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Outer Retinal Tubulation: A Novel Optical Coherence Tomography Finding [Clinical Sciences]

Objective  To describe tubular structures found in the outer retina seen in a variety of retinal disorders.

Methods  Sixty-nine eyes of 63 patients were examined with spectral-domain optical coherence tomography. Optical coherence tomography C-scans were correlated with their corresponding B-scans. The prevalence, number, size, and shape of the tubular structures were determined.

Results  Branching tubules were identified in the outer retina of 54 patients with age-related macular degeneration and in 9 patients with other diagnoses. The tubules appeared as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 40 to 140 µm high and 40 to 2260 µm wide. Morphologic features ranged from single straight or branching tubules to complex cavitary networks, usually overlying areas of pigment epithelial alteration or subretinal fibrosis. The tubules generally remained stable over time. In a retinal practice specializing in advanced age-related macular degeneration, these structures were identified in 60 of 248 patients (24.2%) seen during a 3-month period.

Conclusions  Degenerating photoreceptors may become arranged in a circular or ovoid fashion during a process we propose to term outer retinal tubulation. These changes are apparently common in advanced diseases affecting the outer retina and retinal pigment epithelium. This observation has practical implications because these findings can be misinterpreted as intraretinal or subretinal fluid, possibly prompting unnecessary interventions.

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Comparison of Glaucoma Diagnostic Capabilities of Cirrus HD and Stratus Optical Coherence Tomography [Clinical Sciences]

Objective  To compare the glaucoma diagnostic capabilities offered by Stratus and Cirrus spectral-domain optical coherence tomography (OCT).

Methods  One hundred subjects with glaucoma and 74 healthy subjects were tested by Stratus and Cirrus OCT. Areas under the receiver operating characteristic curves (AUCs) of average, 4-quadrant, and 12-sector retinal nerve fiber layer thicknesses and sensitivities at fixed specificities (80% and 90%) were compared when the 2 OCT modalities were used to evaluate patients with early or moderate to advanced glaucoma. Likelihood ratios using normative classifications were reported.

Results  Overall, both OCT instruments showed similar glaucoma discrimination capability in average retinal nerve fiber layer thickness (AUC, 0.953 [Cirrus] vs 0.934 [Stratus]; P = .15). Cirrus OCT displayed significantly higher AUCs in the average, inferior, temporal, and superior quadrants and 7-o’clock measurements in early stages of glaucoma. The between–OCT instrument AUCs did not differ significantly in moderate to advanced stages. Abnormal results for both OCT instruments, after comparison with their normative databases, were associated with high likelihood ratios.

Conclusions  In our series, the Cirrus OCT showed better glaucoma discrimination capability than Stratus OCT in early stages of glaucoma. Our findings suggest that spectral-domain technology of OCT may offer an improved capability of early-stage glaucoma detection.

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Error in eTable in: Use of Global Visual Acuity Data in a Time Trade-off Approach to Calculate the Cost Utility of Cataract Surgery [Correction]

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Prediction of Glaucomatous Visual Field Loss by Extrapolation of Linear Trends [Clinical Sciences]

Objective  To investigate how well short-term progression rates can predict long-term visual field outcomes in patients with glaucoma.

Methods  We calculated visual field rates of progression using linear regression analysis of the Visual Field Index (VFI) for 100 consecutive patients with glaucoma having 10 or more Swedish Interactive Thresholding Algorithm standard field tests. Final VFI was predicted on the basis of linear extrapolation of the slope defined by the initial 5 field test results. Final VFI also was estimated using linear regression of all qualifying examination results for each patient. Primary outcome measures were the absolute difference and the correlation between predicted and estimated final VFI values.

Results  Patient follow-up averaged 8.2 years and 11 field examinations. Median VFI progression rate was –1.1% per year both for the initial 5 test results and also for the complete series. Seventy percent of patients had a predicted final VFI within ±10% of the estimated final VFI, and the 2 VFI calculations had a correlation coefficient of 0.84.

Conclusion  Linear extrapolation based on 5 initial visual field test results was a reliable predictor of future field loss in most patients. Patients in whom linear regression analysis suggests dangerously rapid rates of visual field progression may be candidates for significant alterations in therapy.

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Errors in Figure and Text in: Inner Retinal Layer Thinning in Parkinson Disease [Correction]

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Contact Lens-Related Adverse Events and the Silicone Hydrogel Lenses and Daily Wear Care System Used [Clinical Sciences]

Objective  To investigate the incidence of adverse events related to the use of varying silicone hydrogel contact lens and lens solution combinations.

Methods  Individuals with myopia (N = 558) participated in 1 or more of approximately 40-participant trials in a matrix of 20 silicone hydrogel contact lens and lens-solution combinations. Visits were at baseline, 2 weeks, 1 month, and 3 months. The mean study completion rate was 90% of the expected participant-months (final data set: 840 lens-solution combinations and 2271 participant-months). Adverse events were reported as the first occurrence of each type per 100 participant-months for each lens-solution combination.

Results  The rate of all corneal infiltrative events (CIEs) was 3.1 per 100 participant-months (range, 0-10.5), and the rate of symptomatic CIEs was 1.7 per 100 participant-months (range, 0-10.5), including 1 case of microbial keratitis (0.04 per 100 participant-months). Rates for CIEs differed substantially among solution groups, with hydrogen peroxide having the lowest rate (0.6 per 100 participant-months; range, 0-0.9). The rate was 0.8 per 100 participant-months (range, 0-8.0) for superior epithelial arcuate lesions, which varied by lens type, 0.04 per 100 participant-months (1 case only) for corneal erosion, and 0.4 per 100 participant-months (range, 0-2.0) for contact lens papillary conjunctivitis, which was modified by type of solution. The rate of solution-induced corneal staining for all lens-solution combinations was 4.7 per 100 participant-months (range, 0-23) and varied significantly based on lens-solution combination (P < .001).

Conclusions  The frequency of adverse events varied with silicone hydrogel contact lens and lens solution combinations, with hydrogen peroxide having the lowest incidence of CIEs and solution-induced corneal staining, indicating that lens material and design, type of solution, and solution-lens interactions are likely contributing factors in this mode of lens wear.

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Essential Role for c-Jun N-Terminal Kinase 2 in Corneal Epithelial Response to Desiccating Stress [Laboratory Sciences]

Objective  To investigate the protective effects of c-Jun N-terminal kinase (JNK)–1 and -2 gene knockout (KO) on the corneal epithelial response to desiccating stress.

Methods  The C57BL/6, JNK1KO, and JNK2KO mice were subjected to desiccating stress (DS) for 5 days. The effects of DS on the corneal epithelium were evaluated by measuring corneal smoothness and permeability. Expression of matrix metalloproteinases (MMP)–1, MMP-9, and cornified envelope protein precursors (small proline-rich protein [SPRR]–1a, SPRR-2a, and involucrin) in the corneal epithelia was evaluated by immunostaining and real-time polymerase chain reaction. Collagenase and gelatinase activity in corneal sections as measured with in situ fluorescent assays.

Results  The JNK2KO mice had smoother corneal surfaces and less corneal barrier disruption in response to DS than JNK1KO mice and C57BL/6 wild-type control mice. The DS increased levels of MMP-1, MMP-9, SPRR-1a, SPRR-2a, involucrin immunoreactivity, and mRNA transcripts in the corneal epithelium of JNK1KO and C57BL/6 mice, but not in JNK2KO mice. Knockout of JNK2 prevented DS-induced increase in gelatinase and collagenase activity in the cornea.

Conclusion  The JNK2 protein appears to have an essential role in desiccation-induced corneal epithelial disease by stimulating production of MMP-1, MMP-9, and cornified envelope precursors.

Clinical Relevance  The JNK2 protein could be a novel therapeutic target in dry eye disease.

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Increased Prevalence of Myopia in the United States Between 1971-1972 and 1999-2004 [Epidemiology]

Objective  To compare US population prevalence estimates for myopia in 1971-1972 and 1999-2004.

Methods  The 1971-1972 National Health and Nutrition Examination Survey provided the earliest nationally representative estimates for US myopia prevalence; myopia was diagnosed by an algorithm using either lensometry, pinhole visual acuity, and presenting visual acuity (for presenting visual acuity ≥20/40) or retinoscopy (for presenting visual acuity ≤20/50). Using a similar method for diagnosing myopia, we examined data from the 1999-2004 National Health and Nutrition Examination Survey to determine whether myopia prevalence had changed during the 30 years between the 2 surveys.

Results  Using the 1971-1972 method, the estimated prevalence of myopia in persons aged 12 to 54 years was significantly higher in 1999-2004 than in 1971-1972 (41.6% vs 25.0%, respectively; P < .001). Prevalence estimates were higher in 1999-2004 than in 1971-1972 for black individuals (33.5% vs 13.0%, respectively; P < .001) and white individuals (43.0% vs 26.3%, respectively; P < .001) and for all levels of myopia severity (>–2.0 diopters [D]: 17.5% vs 13.4%, respectively [P < .001]; ≤–2.0 to >–7.9 D: 22.4% vs 11.4%, respectively [P < .001]; ≤–7.9 D: 1.6% vs 0.2%, respectively [P < .001]).

Conclusions  When using similar methods for each period, the prevalence of myopia in the United States appears to be substantially higher in 1999-2004 than 30 years earlier. Identifying modifiable risk factors for myopia could lead to the development of cost-effective interventional strategies.

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Sociodemographic, Lifestyle, and Medical Risk Factors for Visual Impairment in an Urban Asian Population: The Singapore Malay Eye Study [Epidemiology]

Objective  To describe the associations between sociodemographic, lifestyle, and medical risk factors and visual impairment in a Southeast Asian population.

Methods  Population-based cross-sectional study of 3280 (78.7% response rate) Malay Singaporeans aged 40 to 80 years. Participants underwent a standardized interview, in which detailed sociodemographic histories were obtained, and clinical assessments for presenting and best-corrected visual acuity. Visual impairment (logMAR > 0.30) was classified as unilateral (1 eye impaired) or bilateral (both eyes impaired). Analyses used multivariate-adjusted multinomial logistic regression.

Results  Older age and lack of formal education was associated with increased odds of both unilateral and bilateral visual impairment based on presenting and best-corrected visual acuity. The odds doubled for each decade older, and lower education increased the odds 1.59- to 2.83-fold. Bilateral visual impairment was associated with being unemployed (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.30-2.60), widowed status (OR, 1.51; 95% CI, 1.13-2.01), and higher systolic blood pressure (OR, 1.96; 95% CI, 1.44-2.66). Diabetes was associated with unilateral (OR, 1.47; 95% CI, 1.10-1.95) and bilateral (OR, 1.69; 95% CI, 1.23-2.32) visual impairment using best-corrected visual acuity.

Conclusions  Older age, lower education, unemployment, being widowed, diabetes, and hypertension were independently associated with bilateral visual impairment. Public health interventions should be targeted to these at-risk populations.

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Error in Figure in: A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study Report 5 [Correction]

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Clinical Presentation and Genetic Correlation of Patients With Mutations Affecting the FZD4 Gene [Ophthalmic Molecular Genetics]

Objective  To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the FZD4 gene.

Methods  A total of 123 patients diagnosed with autosomal-dominant familial exudative vitreoretinopathy (AdFEVR) or retinopathy of prematurity (ROP) and 42 control patients were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination or during ROP screening. Genomic DNA was isolated and polymerase chain reaction and direct sequencing of the FZD4 gene performed.

Results  FZD4 gene mutations were discovered in 13 of the 123 (10.6%) patients. Nine of the 63 patients with AdFEVR (14.3%) has mutations in the FZD4 gene. Four heterozygous mutations were identified: C117R, C181Y, Q505X, and P33S/P168S. Four of the 60 patients with ROP (6.7%) have a double missense mutation P33S/P168S that was also found in the patients with FEVR. No other FZD4 mutations were found in the patients with ROP. Additionally, patients expressing the double mutation had clinical presentations that overlapped, making it difficult to assign a definitive diagnosis. None of the mutations found in the patients with FEVR or ROP were seen in the control chromosomes.

Conclusion  Mutations occurring in the FZD4 gene affect patients diagnosed with both FEVR and ROP. The clinical picture often overlaps and may require a detailed birth and family history for diagnosis. Genetic testing confirms inherited vitreoretinopathy and helps direct clinical management.

Clinical Relevance  Patients diagnosed with ROP may have a mutation in the FZD4 gene and display characteristics consistent with FEVR. Analysis of the FZD4 gene should be considered.

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Error in Figure and Text in: A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Standard Care to Treat Vision Loss Associated With Macular Edema Secondary to Branch Retinal Vein Occlusion [Correction]

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Adverse Events After Pars Plana Vitrectomy Among Medicare Beneficiaries [Socioeconomics and Health Services]

Objectives  To assess the complication rates of pars plana vitrectomy (PPV) among older Americans and to determine whether rates of adverse events and additional operations have changed during the past decade.

Methods  Claims data were reviewed to identify all adults aged 68 years or older in the 5% Medicare sample who underwent their first PPV during 1994-1995, 1999-2000, and 2004-2005. One-year rates of severe complications (endophthalmitis, suprachoroidal hemorrhage, or retinal detachment), less severe complications, receipt of an additional operation, and blindness were calculated and compared among the 3 groups using Cox regression. Analyses were adjusted for prior adverse events (during the previous 3 years), demographic characteristics, and comorbid conditions.

Results  The 1994-1995, 1999-2000, and 2004-2005 cohorts had 3263, 5064, and 5263 patients, respectively. The 1-year severe complication rates did not differ among the 3 groups (range, 4.8%-5.5%). The hazard of a less severe complication or an additional operation was higher in the 2004-2005 cohort than in the earlier cohorts (P < .05 for all comparisons). The hazard of endophthalmitis was higher in black individuals (P = .07) and those of other races (P = .02) than in white patients.

Conclusions  During the past decade, rates of severe complications after PPV remained stable, but rates of less severe complications and subsequent operations increased. Future studies should explore the potential factors that explain these changes and the alarming elevated incidence of post-PPV endophthalmitis among nonwhite individuals.

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Swan M. Burnett, MD, PhD: The Forgotten Father of Little Lord Fauntleroy [Special Article]

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Intravitreal Corticosteroids for Diabetic Retinopathy Prevention [Editorial]

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Bringing Better Treatments to Patients Faster by Expanding Access [Editorial]

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The 100 Most Influential Journals [Editorial]

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July 2009 Archives Web Quiz Winner [Archives Web Quiz Winner]

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Summary Results and Recommendations From the Age-Related Eye Disease Study [Clinical Trial Retrospective]

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Legacy of the Age-Related Eye Disorder Study [Clinical Trial Retrospective]

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Liquid Nitrogen Cryotherapy of Conjunctival Lymphangiectasia: A Case Series [Research Letters]

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Macular Hole Closure and Visual Improvement With Topical Nonsteroidal Treatment [Research Letters]

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Ocular Vaccinia With Severe Restriction of Extraocular Motility [Research Letters]

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Bitemporal Hemianopia Caused by Retinal Disease [Research Letters]

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