Ophthalmology

Editorial Board

2010-03-01

This Issue At A Glance

Lori Baker Schena, John Kerrison — 2010-03-01

In a population-based prospective cohort study, Lindblad et al (p. 424) found a statistically significant positive association between hormone replacement therapy (HRT) and the risk of cataract extraction. This increased risk was higher in current users of HRT with longer duration of use, compared with women who never used HRT. In addition, current users of HRT consuming more than 1 alcoholic beverage per day had further increased risk of cataract extraction. The study involved 30 861 postmenopausal women aged 40 to 83 participating in the Swedish Mammography Cohort who completed a self-administered questionnaire in 1997 about hormone status and HRT. They were followed up through October 2005. In the multivariate adjusted analysis, previous use of HRT was associated with a 14% increased risk of cataract extraction compared with those who never used HRT, and current use was associated with an 18% increased risk. The authors conclude that if these findings are confirmed, an increased rate of cataract extraction may be yet another potential negative outcome associated with HRT.

2010-03-01

A Tale of Two Systems: Health Reform in China and the United States

Nathan G. Congdon, Tin Aung — 2010-03-01

The 9-province survey of Zhao et al, provides new evidence of the burden of vision disability facing rural China. The prevalence of presenting blindness among persons 50 years of age and older exceeds 2%, while 1 in 10 persons are visually impaired. Mild impairment, in the range of 20/40 to 20/63, is of increasing importance in an age when the ability to drive and read a computer screen are requirements of day-to-day life for many Chinese citizens; more than a quarter of persons in the economic vanguard Guangdong province suffer from such impairment. Women and those without formal education are at the highest risk for all levels of visual disability.

Prevalence of Vision Impairment in Older Adults in Rural China: The China Nine-Province Survey

2010-01-15

Purpose: Describe the prevalence of visual impairment/blindness among older adults in rural populations in China.Design: Population-based, cross-sectional study.Participants: We evaluated 45 747 adults ≥50 years of age.Methods: Geographically defined cluster sampling was used in randomly selecting a cross-section of residents from a representative rural county within each of 9 provinces in mainland China. Participants were enumerated through village registers followed by door-to-door household visits. Eligible persons were invited to local examination sites for visual acuity (VA) testing and eye examination.Main Outcome Measures: Presenting and best-corrected distance VA.Results: Of 50 395 enumerated eligible persons, 45 747 (90.8%) were examined and tested for VA. The prevalence of presenting visual impairment <20/63 to ≥20/400 in the better eye was 10.8% and blindness (<20/400) was 2.29%. Across the 9 provinces, presenting visual impairment ranged from 6.89% to 15.8%, and blindness from 1.27% to 5.40%. With best-corrected VA, the prevalence of visual impairment was 5.30%, and 1.93% for blindness. The ranges across the 9 provinces were 3.13% to 9.51% for visual impairment and 0.74% to 4.95% for blindness. Visual impairment and blindness were associated with older age, female gender, lack of education, and geographic area (province) with both presenting and best-corrected VA.Conclusions: Visual impairment and blindness are important public health problems in rural China, with significant regional variations in prevalence. Blindness prevention programs targeting the rural elderly should be expanded, particularly in areas with limited access and affordability of eye care services. Special emphasis should be given to reaching women and those without education. Greater attention should also be given to correction of refractive error.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Distribution of Axial Length and Ocular Biometry Measured Using Partial Coherence Laser Interferometry (IOL Master) in an Older White Population

2009-12-24

Purpose: We aimed to describe norms for the distribution of axial length (AL) and other ocular biometric parameters in an older Caucasian population, measured using partial coherence laser interferometry (Zeiss IOL Master; Carl Zeiss AG, Oberkochen, Germany), a technique now routinely used in measuring AL before cataract surgery. We also aimed to assess age and gender relationships with these parameters and their correlations with spherical equivalent refraction (SER).Design: Cross-sectional analysis of the Blue Mountains Eye Study (BMES) cohort at the examinations (10-year follow-up examination).Participants: From 2002 to 2004, 1952 persons (76% of surviving baseline BMES participants) aged 59 years or older had ocular biometry measured at the 10-year examinations.Methods: Spherical equivalent refraction was calculated as the sum of sphere +0.5 cylinder power, after protocol refraction. Measurements of AL, corneal curvature (K1), anterior chamber depth (ACD), and corneal diameter (WTW) were performed using the IOL Master. Only right phakic eyes (n = 1335) with biometry data were included.Main Outcome Measures: Axial length distribution.Results: Mean AL was 23.44 mm (95% confidence interval [CI], 23.38–23.50) and was greater in men, 23.76 mm (CI, 23.68–23.84), than in women, 23.19 mm (CI, 23.11–23.27). The mean K1, ACD, and WTW were 43.42 diopters (D), 3.10 mm, and 12.06 mm, respectively. The AL and ACD distributions were both positively skewed and peaked, whereas the WTW and K1 distributions were near normal. From age 59 years or older, a mean reduction in AL with age was observed (P for trend = 0.005), 0.12 mm per decade (P = 0.0176) in women but only 0.02 mm per decade (P = 0.6319) in men. Mean SER was 0.58 D, and the distribution was peaked with a negative skew. The SER was negatively correlated with both AL (beta coefficient –0.688) and ACD (beta coefficient −0.222), but not with K1 or WTW.Conclusions: These data provide normative values in the older general population for AL measured using the IOL Master. Axial length distribution was peaked and skewed, suggesting an active modulation process.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Hormone Replacement Therapy in Relation to Risk of Cataract Extraction: A Prospective Study of Women

Birgitta Ejdervik Lindblad, Niclas Håkansson, Bo Philipson, Alicja Wolk — 2010-01-04

Objective: To investigate the association between hormone replacement therapy (HRT) and the incidence of cataract extraction among postmenopausal women.Design: Population-based, prospective cohort study.Participants: A total of 30 861 postmenopausal women participating in the Swedish Mammography Cohort, age 49 to 83 years, who completed a self-administered questionnaire in 1997 about hormone status, HRT, and lifestyle factors.Methods: The women were followed from September 1997 through October 2005. The cohort was matched with registers of cataract extraction in the study area.Main Outcome Measures: Incident operative extraction of age-related cataract.Results: We identified 4324 incident cases of cataract extractions during 98 months of follow-up. In multivariate adjusted analysis, ever use of HRT was associated with a 14% increased risk of cataract extraction (rate ratio [RR], 1.14; 95% confidence interval [CI], 1.07–1.21) compared with those who never used HRT. Current use of HRT was associated with an 18% increased risk of cataract extraction (RR, 1.18; 95% CI, 1.10–1.26). A significant linear trend was observed where increasing duration of HRT usage resulted in an increased risk of cataract extraction (P for trend = 0.006). Multivariate RR for current HRT usage for >10 years was 1.20 (95% CI, 1.06–1.36; P for trend = 0.001). Among women drinking on average >1 drink of alcohol per day, current HRT users had a 42% increased risk (RR, 1.42; 95% CI, 1.11–1.80) for cataract extraction, compared with women who neither used HRT nor alcohol. The risk of cataract extraction among current users of HRT was similar among current smokers and those who never smoked.Conclusions: Our prospective, population-based study indicates that postmenopausal women using HRT for a long period of time may be at an increased risk for cataract extraction, especially those drinking >1 alcoholic drink daily.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Limbal Stem Cell Deficiency after Topical Mitomycin C Therapy for Primary Acquired Melanosis with Atypia

Alejandro Lichtinger, Jacob Pe'er, Joseph Frucht-Pery, Abraham Solomon — 2010-01-08

Purpose: To describe the incidence, characteristics, risk factors, and clinical outcome of limbal stem cell deficiency (LSCD) resulting from topical treatment with mitomycin C (MMC) for primary acquired melanosis (PAM) with atypia.Design: Retrospective, observational case series.Participants: Patients with LSCD who had been managed with topical MMC for PAM with atypia at the Ocular Oncology Service at the Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, between 2000 and 2007.Methods: Retrospective chart review of all patients with PAM with atypia was performed. Impression cytologic analysis of the corneal and conjunctival epithelium was performed in patients suspected of having LSCD.Main Outcome Measures: Evaluation of risk factors for LSCD, including demographic characteristics, MMC dosage, and length of treatment; and clinical and visual outcome of patients diagnosed with LSCD.Results: Limbal stem cell deficiency was identified in 5 (23.8%) of 21 patients. The mean age±standard deviation of the 5 patients was 61.8±12.7 years compared with 43.7±16.1 years in patients in whom this complication did not develop (P = 0.025). Longer treatment periods of MMC were noted in eyes in which LSCD developed (78.4±24.8 days) compared with eyes without LSCD (37.7±3.1 days; P = 0.07). In 3 patients, spontaneous partial resolution of the LSCD was noted.Conclusions: High-dose topical MMC for PAM with atypia may be associated with a relatively high incidence of LSCD. Mitomycin C concentration and treatment regimen should be reevaluated to improve the safety of this treatment protocol.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Descemet's Stripping Automated Endothelial Keratoplasty Outcomes Compared with Penetrating Keratoplasty from the Cornea Donor Study

2009-12-24

Purpose: To assess outcomes 1 year after Descemet's stripping automated endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty (PKP) from the Specular Microscopy Ancillary Study (SMAS) of the Cornea Donor Study.Design: Multicenter, prospective, nonrandomized clinical trial.Participants: A total of 173 subjects undergoing DSAEK for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema) compared with 410 subjects undergoing PKP from the SMAS who had clear grafts with at least 1 postoperative specular image within a 15-month follow-up period.Methods: The DSAEK procedures were performed by 2 experienced surgeons per their individual techniques, using the same donor and similar recipient criteria as for the PKP procedures in the SMAS performed by 68 surgeons at 45 sites, with donors provided from 31 eye banks. Graft success and complications for the DSAEK group were assessed and compared with the SMAS group. Endothelial cell density (ECD) was determined from baseline donor, 6-month (range, 5–7 months), and 12-month (range, 9–15 months) postoperative central endothelial images by the same reading center used in the SMAS.Main Outcome Measures: Endothelial cell density and graft survival at 1 year.Results: Although the DSAEK recipient group criteria were similar to the PKP group, Fuchs' dystrophy was more prevalent in the DSAEK group (85% vs. 64%) and pseudophakic corneal edema was less prevalent (13% vs. 32%, P<0.001). The regraft rate within 15 months was 2.3% (DSAEK group) and 1.3% (PKP group) (P = 0.50). Percent endothelial cell loss was 34±22% versus 11±20% (6 months) and 38±22% versus 20±23% (12 months) in the DSAEK and PKP groups, respectively (both P<0.001). Preoperative diagnosis affected endothelial cell loss over time; in the PKP group, the subjects with pseudophakic/aphakic corneal edema experienced significantly higher 12-month cell loss than the subjects with Fuchs' dystrophy (28% vs. 16%, P = 0.01), whereas in the DSAEK group, the 12-month cell loss was comparable for the 2 diagnoses (41% vs. 37%, P = 0.59).Conclusions: One year post-transplantation, overall graft success was comparable for DSAEK and PKP procedures and endothelial cell loss was higher with DSAEK.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Detection of Bacterial Endosymbionts in Clinical Acanthamoeba Isolates

Alfonso Iovieno, Dolena R. Ledee, Darlene Miller, Eduardo C. Alfonso — 2009-12-24

Purpose: To determine the presence of 4 clinically relevant bacterial endosymbionts in Acanthamoeba isolates obtained from patients with Acanthamoeba keratitis (AK) and the possible contribution of endosymbionts to the pathogenesis of AK.Design: Experimental study.Participants: Acanthamoeba isolates (N = 37) recovered from the cornea and contact lens paraphernalia of 23 patients with culture-proven AK and 1 environmental isolate.Methods: Acanthamoeba isolates were evaluated for the presence of microbial endosymbionts belonging to the bacterial genera Legionella, Pseudomonas, Mycobacterium, and Chlamydia using molecular techniques (polymerase chain reaction and sequence analysis, fluorescence in situ hybridization) and transmission electron microscopy. Corneal toxicity and virulence of Acanthamoeba isolates with and without endosymbionts were compared using a cytopathic effect (CPE) assay on human corneal epithelial cells in vitro. Initial visual acuity, location and characteristics of the infiltrate, time to detection of the infection, and symptom duration at presentation were evaluated in all patients.Main Outcome Measures: Prevalence and potential pathobiology of bacterial endosymbionts detected in Acanthamoeba isolates recovered from AK.Results: Twenty-two (59.4%) of the 38 cultures examined contained at least 1 bacterial endosymbiont. One isolate contained 2 endosymbionts, Legionella and Chlamydia, confirmed by fluorescence in situ hybridization. Corneal toxicity (CPE) was significantly higher for Acanthamoeba-hosting endosymbionts compared with isolates without endosymbionts (P<0.05). Corneal pathogenic endosymbionts such as Pseudomonas and Mycobacterium enhanced Acanthamoeba CPE significantly more than Legionella (P<0.05). In the presence of bacterial endosymbionts, there was a trend toward worse initial visual acuity (P>0.05), central location (P<0.05), absence of radial perineuritis (P<0.05), delayed time to detection (P>0.05), and longer symptom duration at presentation (P>0.05).Conclusions: Most Acanthamoeba isolates responsible for AK harbor 1 or more bacterial endosymbionts. The presence of endosymbionts enhances the corneal pathogenicity of Acanthamoeba isolates and may impact detection time and clinical features of AK.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Screening for Glaucoma in High-Risk Populations Using Optical Coherence Tomography

2009-12-24

Objective: To estimate the diagnostic accuracy of Stratus optical coherence tomography (OCT) for glaucoma screening in high-risk populations.Design: Cross-sectional evaluation of a diagnostic test for screening.Participants: Three hundred thirty-three community-based volunteer participants with risk factors for glaucoma.Methods: The optic nerve and peripapillary retinal nerve fiber layer (RNFL) of participants' eyes were scanned using the Stratus OCT. Based on an ophthalmologic examination and frequency doubling perimetry, eyes were classified into 4 categories: normal, possible glaucoma, probable glaucoma, and definitive glaucoma.Main Outcome Measures: The sensitivities, specificities, positive and negative likelihood ratios of the RNFL, optic disc parameters, and their combinations were calculated.Results: The right eyes were retained for analyses. After excluding eyes with missing data or with poor quality scans, the data of 210 right eyes were analyzed. Six eyes had definitive glaucoma. Combining the best performing optic nerve head parameters (cup diameter or cup/disc vertical ratio or cup/disc area ratio) and RNFL parameters (superior average or inferior average or overall average) using AND-logic resulted in a sensitivity of 67% (95% confidence interval [CI], 24%–94%), specificity of 96% (95% CI, 92%–98%), a positive likelihood ratio of 17.08 (95% CI, 7.06–41.4), and a negative likelihood ratio of 0.35 (95% CI, 0.11–1.08).Conclusions: When adequate quality scans may be obtained, the Stratus has moderate sensitivity and high specificity for definitive glaucoma. Specificity is increased when parameters from both the optic nerve head and RNFL scans are combined.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

2009-12-24

Purpose: To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression.Design: Observational cohort study.Participants: The study included 453 eyes from 252 individuals followed for an average of 46±14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy.Methods: Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders.Main Outcome Measures: Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC1 coefficient.Results: Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC1 coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94–0.97) and 0.44 (0.28–0.61), respectively.Conclusions: The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Simvastatin and Disease Stabilization in Normal Tension Glaucoma: A Cohort Study

2010-01-04

Purpose: To investigate whether simvastatin use is associated with visual field (VF) stabilization in patients with normal tension glaucoma (NTG).Design: Prospective cohort study (ClinicalTrials.gov Identifier: NCT00321386).Participants: A total of 256 eyes from 256 Chinese subjects with NTG.Methods: Patients were followed up at 4-month intervals for 36 months for VF progression per Anderson's criteria. Clinical parameters were checked for association with progression in multivariate analysis.Main Outcome Measures: The primary outcome was the association between simvastatin use and VF progression.Results: Thirty-one patients (12.1%) were taking simvastatin (statin+), and 225 patients (87.9%) were not taking simvastatin (statin−). Baseline age, gender, untreated intraocular pressure, VF indices, vertical cup-to-disc ratio, and central corneal thickness (CCT) were comparable between the 2 groups. There were significantly more patients with a history of hypercholesterolemia, systemic hypertension, and ischemic heart disease in the statin+ group. A total of 121 patients (47.3%) showed evidence of VF progression (mean rate of mean deviation loss was −0.30 decibel per year) during the 36 months of follow-up. Simvastatin use was among 8 of 121 patients (6.6%) who progressed compared with 23 of 135 patients (17.0%) who did not progress (P = 0.011). Logistic regression revealed that history of disc hemorrhage (relative risk [RR] 3.26; 95% confidence interval [CI], 1.21–8.76; P = 0.019), history of cerebrovascular accidents (RR 2.28; 95% CI, 1.03–5.06; P = 0.043), and baseline age (per 10 years older; RR 1.38; 95% CI, 1.08–1.76; P = 0.009) were significant risk factors for VF progression, whereas simvastatin use conferred a protective effect (RR 0.36; 95% CI, 0.14–0.91; P = 0.030).Conclusions: Simvastatin use may be associated with VF stabilization in patients with NTG. A larger scale randomized controlled trial and cost-effectiveness analyses seem warranted.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Chronic Kidney Disease and Intraocular Pressure: The Singapore Malay Eye Study

2009-12-07

Purpose: To examine the relationship of chronic kidney disease (CKD) with intraocular pressure (IOP) and glaucoma in Malay adults in Singapore.Design: Population-based, cross-sectional study.Participants: We included 3280 (78.8% response rate) Malay adults aged 40 to 79 years living in Singapore.Methods: Participants underwent a standardized interview, ocular examination, imaging, and laboratory investigations. Goldmann applanation tonometry was used to measure IOP. Glaucoma was diagnosed using the International Society of Geographic and Epidemiological Ophthalmology classification. Non-fasting serum glucose, glycosylated hemoglobin, and creatinine were obtained from all participants. Estimated glomerular filtration rate (eGFR) and microalbuminuria were also determined. We defined CKD as eGFR < 60 ml/min/1.73 m2 or presence of micro/macroalbuminuria, defined as urinary albumin-to-creatinine ratio ≥17 mg/g for men and ≥25 mg/g for women.Main Outcome Measures: We assessed CKD, IOP, and glaucoma.Results: The overall prevalence of CKD was 27.92% and glaucoma 4.5%. The mean (standard deviation [SD]) IOP was 15.41 (3.7) mmHg. After adjustments for age and gender, IOP was significantly higher in participants with CKD compared with those without CKD (15.8 vs 15.3 mmHg; P<0.0001). The IOP was also higher with lower levels of eGFR (P<0.001). These associations remained significant in separate stratified analyses of persons with and without diabetes, glaucoma, or both. In multiple linear regression models, persons with CKD had on average IOP that was 0.305 mmHg higher than that of persons without CKD. No association between CKD and glaucoma (age and gender adjusted odds ratio [OR], 0.82; 95% confidence interval [CI], 0.56–1.20; and multivariate adjusted OR, 0.87; 95% CI, 0.58–1.29) was found.Conclusions: Our population-based study in Malay adults showed that CKD is associated with higher IOP, independent of age, diabetes, and glaucoma status.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

The Incidence of Retinal Vein Occlusion in the Ocular Hypertension Treatment Study

2009-12-24

Objective: To determine the incidence of retinal vein occlusion (RVO) in the Ocular Hypertension Treatment Study (OHTS).Design: Retrospective analysis of data from a randomized clinical trial.Participants: We included 1636 ocular hypertensive participants with a mean follow-up of 9.1 years. Participants in the medication and observation groups were managed according to their original randomization assignment until June 1, 2002. At that time, the observation participants were offered ocular hypotensive treatment. Data to July 1, 2005, are included in this report.Methods: Occurrences of RVO in study participants, categorized as branch, central or hemicentral vein occlusion, were documented. Potential RVO events were identified by a keyword search of Adverse Event Reports, the Optic Disc Reading Center database, Endpoint Committee reviews, and by response to a written request for information sent to each clinical site. To confirm a potential RVO, the complete OHTS chart was reviewed. Statistical analyses included t tests, chi-square tests and Cox proportional hazards models.Main Outcome Measures: Incidence of RVO.Results: Twenty-six RVOs—5 branch, 14 central, and 7 hemicentral RVOs—were confirmed in 23 participants (15 observation and 8 medication). The 10-year cumulative incidence of RVO was 2.1% in the observation group and 1.4% in the medication group (P = 0.14; log-rank test). At baseline, participants who later developed a RVO were significantly older (65.1 vs 55.3 years; P = 0.01), and had greater horizontal cup-to-disc ratios (P = 0.0004).Conclusions: Although the incidence of RVO was higher in the observation group than the medication group, this difference did not attain significance. Consistent with some previous studies, older age and greater cup-to-disc ratio were associated with the development of RVO.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Natural History of Drusenoid Pigment Epithelial Detachment in Age-Related Macular Degeneration: Age-Related Eye Disease Study Report No. 28

2010-01-15

Objective: To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD).Design: Multicenter, clinic-based, prospective cohort study.Participants: Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED.Methods: Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan–Meier analyses of progression to advanced AMD and of moderate vision loss (≥15 letters compared with baseline) were performed.Main Outcome Measures: Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing ≥15 letters).Results: A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by ≥15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters (∼20/30) at baseline to 61 letters (∼20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes.Conclusions: The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD, progressive development of pigmentary changes and calcified drusen were observed. Decline of visual acuity is a common outcome, with or without progression to advanced forms of AMD.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

The Complement Component 5 Gene and Age-Related Macular Degeneration

2009-12-21

Objective: To investigate the association between variants in the complement component 5 (C5) gene and age-related macular degeneration (AMD).Design: Separate and combined data from 3 large AMD case-control studies and a prospective population-based study (The Rotterdam Study).Participants: A total of 2599 AMD cases and 3458 ethnically matched controls.Methods: Fifteen single nucleotide polymorphisms (SNPs) spanning the C5 gene were initially genotyped in 375 cases and 199 controls from The Netherlands (The Amsterdam/Rotterdam-Netherlands [AMRO-NL] study population). Replication testing of selected SNPs was performed in the Rotterdam Study (NL) and study populations from Southampton, United Kingdom (UK), and New York, United States (US).Main Outcome Measures: Early and late stages of prevalent and incident AMD, graded according to (a modification of) the international grading and classification system of AMD.Results: Significant allelic or genotypic associations between 8 C5 SNPs and AMD were found in the AMRO-NL study and this risk seemed to be independent of CFH Y402H, LOC387715 A69S, age, and gender. None of these findings could be confirmed consistently in 3 replication populations.Conclusions: Although the complement pathway, including C5, plays a crucial role in AMD, and the C5 protein is present in drusen, no consistent significant associations between C5 SNPs and AMD were found in any of these studies. The implications for genetic screening of AMD are discussed.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Severe Intraocular Inflammation after Intravitreal Injection of Bevacizumab

2009-12-24

Purpose: To report 5 cases of severe intraocular inflammation that developed after an intravitreal injection of the same lot of bevacizumab.Design: Retrospective case series.Participants: Patients treated with an intravitreal injection of bevacizumab (lot B3003B01).Methods: The clinical charts of 35 eyes of 35 consecutive patients who were treated with intravitreal injection of lot B3003B01 bevacizumab from December 18, 2008, through January 20, 2009, were reviewed.Main Outcome Measures: Incidence of intraocular inflammation, results of bacterial cultures, best-corrected visual acuity (BCVA), and endothelial cell density.Results: Five (14.3%) of the 35 cases had severe intraocular inflammation, and the inflammation had some characteristics of toxic anterior segment syndrome (TASS). Five of the 5 cases had a predominantly anterior chamber reaction, and 4 of the 5 cases were accompanied by hypopyon. Undiluted samples collected from both the aqueous and vitreous of the 5 cases were culture negative. The BCVA was 0.66±0.29 (mean±standard deviations) logarithm of the minimum angle resolution (logMAR) units, and the endothelial cell density was 2683.6±97.3/mm2 before the intravitreal bevacizumab. At the final visit, the BCVA was 0.44±0.36 logMAR units, and the cell density was 2679.0±217.5/mm2. These differences were not significant (P = 0.171 and 0.964).Conclusions: These observations indicate that an intravitreal injection of bevacizumab can induce sterile endophthalmitis that has characteristics of TASS.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Impact of Coagulation-Balance Gene Predictors on Efficacy of Photodynamic Therapy for Choroidal Neovascularization in Pathologic Myopia

2009-12-30

Purpose: To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM).Design: Retrospective, consecutive, nonrandomized, interventional cases series.Participants: Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV.Methods: The enrolled patients were subdivided as responders or nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were genotyped by polymerase chain reaction in each patient.Main Outcome Measures: The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV leakage, greatest linear dimension, and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient's age, baseline visual acuity, and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy.Results: Responders to PDT-V were overrepresented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.8–5.4; P = 0.001) and, to a minor extent, among patients with better visual acuity at baseline (OR, 11.8; 95% CI, 1.6–88.0; P = 0.02). However, predictors of PDT-V lack of efficacy were patient's age (OR, 0.73; 95% CI, 0.62–0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR, 0.19; 95% CI, 0.11–0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V.Conclusions: These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Are Myopic Eyes Less Likely to Have Diabetic Retinopathy?

2009-12-24

Purpose: Eyes with myopia may be less likely to develop diabetic retinopathy (DR). The relationship between refractive error, ocular biometry, and DR therefore was investigated.Design: Population-based, cross-sectional study.Participants: Persons with diabetes from the Singapore Malay Eye Study (SiMES).Methods: Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more, use of diabetic medication, or a physician diagnosis of diabetes. Spherical equivalent refraction (SE) was assessed using an autokeratorefractometer and subjective refraction. Axial length (AL) and anterior chamber depth (ACD) were measured by IOLMaster (Carl Zeiss Meditec AG, Jena, Germany). Diabetic retinopathy was graded from retinal photographs.Main Outcome Measures: Any DR was defined by characteristic lesions defined by the Early Treatment Diabetic Retinopathy Study (ETDRS); moderate DR by ETDRS retinopathy severity scores of 43 or higher; and vision-threatening retinopathy by severe nonproliferative retinopathy, proliferative DR, or clinically significant macular edema.Results: Of 3280 adult Malay participants (78.7% response), 629 persons with diabetes contributed to this analysis. In multivariate analyses adjusting for age, gender, education, height, cataract, hypertension, hemoglobin A1c, and other factors, eyes with myopic SE were less likely to have any DR (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.84–0.96; P = 0.002, per 1-diopter [D] decrease), moderate DR (OR, 0.83; 95% CI, 0.73–0.93; P = 0.001, per 1-D decrease), and vision-threatening DR (OR, 0.77; 95% CI, 0.67–0.88; P<0.001, per 1-D decrease). Eyes with longer AL were less likely to have any DR (OR, 0.86; 95% CI, 0.75–0.99; P = 0.041, per 1-mm increase), moderate DR (OR, 0.80; 95% CI, 0.62–1.05; P = 0.11, per 1-mm increase), and vision-threatening DR (OR, 0.63; 95% CI, 0.40–0.99; P = 0.044, per mm increase). Eyes with deeper ACD were less likely to have moderate DR (OR, 0.32; 95% CI, 0.16–0.64; P = 0.001, per 1-mm increase) and vision-threatening DR (OR, 0.14; 95% CI, 0.06–0.36; P = 0.001, per 1-mm increase).Conclusions: Myopic refraction and longer AL are associated with a lower risk of DR, particularly vision-threatening retinopathy, without any evidence of a threshold.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinopathy in Persons without Diabetes: The Handan Eye Study

2009-12-24

Purpose: To describe the prevalence and associations of retinopathy in a population-based nondiabetic sample of rural Chinese.Design: Population-based cross-sectional study.Participants: We included 6830 Han Chinese aged ≥30 years from 13 villages of Yongnian County, Handan City, Hebei Province, China.Methods: All participants underwent a standardized interview and extensive examinations including retinal photography, measurement of blood pressure (BP) and fasting plasma glucose (FPG). Diabetes mellitus was defined as either FPG ≥ 7.0 mmol/l, use of diabetic medication or a physician diagnosis of diabetes. Photographic grading of retinopathy followed the modified Early Treatment Diabetic Retinopathy Study classification system. Logistic regression models were used to assess associations of retinopathy.Main Outcome Measures: Any retinopathy.Results: The prevalence of retinopathy among participants without diabetes was 13.6% (95% confidence interval [CI], 12.6–14.6%). The age and gender standardized prevalence of retinopathy in the Chinese adult population (aged 30+ years) without diabetes was estimated to be 12.1% (95% CI 11.1–12.9%). Independent risk factors associated with retinopathy were age (odds ratio [OR], 1.02 ; 95% CI 1.01–1.03 per year increase), male gender (male vs. female, OR 1.27; 95% CI 1.08–1.49), higher FPG (OR 1.30; 95% CI 1.11–1.53 per mmol/l increase), higher systolic BP (OR 1.15; 95% CI 1.05–1.27 per 10 mmHg increase) and higher diastolic BP (OR 1.16; 95% CI 1.09–1.22 per 10 mmHg increase).Conclusions: Retinopathy was common among rural Chinese adults without diabetes. Its association with FPG and BP suggests that early microvascular damage is occurring at “high normal” levels of blood glucose and BP.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

In Vivo Retinal Morphology after Grid Laser Treatment in Diabetic Macular Edema

2010-01-04

Purpose: To analyze immediate in vivo intraretinal morphologic changes secondary to standardized grid photocoagulation using spectral domain optical coherence tomography (SD OCT).Design: Prospective clinical trial.Participants: Thirteen consecutive patients with treatment-naïve clinically significant diabetic macular edema (DME).Methods: Before and 1 day after standardized grid photocoagulation using the PASCAL system (Pattern Scan Laser, OptiMedica Corporation, Santa Clara, CA), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) examinations based on an eye-tracking system, infrared fundus imaging, color fundus photography, and biomicroscopy were performed. A standardized visual acuity assessment (Early Treatment Diabetic Retinopathy Study protocol) and fluorescein angiography were performed at baseline.Main Outcome Measures: Morphologic changes secondary to grid laser treatment.Results: One day after laser therapy, immediate morphologic alterations of only the outer retinal layers, that is, the retinal pigment epithelium (RPE), the photoreceptor layer (PRL), and the outer nuclear layer (ONL), were observed. The shape of the laser-induced lesions did not show a sagittal alteration pattern throughout all 3 of the layers, however, but rather seemed to follow an oblique pathway throughout the ONL, changing direction at the level of the external limiting membrane and proceeding sagittally through the PRL and RPE. These morphologic changes also induced biometric changes, such as a decrease in central retinal thickness combined with local thickening at the lesion site, especially in the PRL.Conclusions: Spectral domain optical coherence tomography provides new insight into the immediate morphologic changes after laser treatment using the PASCAL laser system. Standardized grid photocoagulation induces characteristic homogenous alteration in the neurosensoric retinal layers. Biometric changes, indicating an immediate effect, were observed within 1 day after treatment.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

High-Resolution Imaging of the Human Retina In Vivo after Scatter Photocoagulation Treatment Using a Semiautomated Laser System

2009-12-24

Purpose: To image the ultrastructural morphology of retinal laser effects and their healing response in vivo using spectral domain optical coherence tomography (SD-OCT).Design: Prospective, interventional study.Participants: Ten patients undergoing panretinal photocoagulation for proliferative diabetic retinopathy.Methods: Panretinal photocoagulation (PRP) was performed using a semiautomated patterned scanning laser system providing a raster of effects with homogenous intensity. Retinal morphology and localization of effects owing to laser–tissue interaction were imaged at 1 day, 1 week, and at monthly intervals for 6 months. The characteristic, specific structural changes during the healing process were followed over time using an SD-OCT device (Spectralis OCT) allowing for high-resolution raster scanning of the entire lesion pattern with identification of identical retinal sites (tracking modality).Main Outcome Measures: Retinal morphology and localization of effects of photocoagulation on SD-OCT images.Results: At day 1 after PRP, the photocoagulation effects were sharply delineated from the surrounding unaffected retina and all spots seemed to be identical in size and location. The area of tissue destruction was confined to the outer retinal layers, extending from the outer nuclear layer (ONL) to the retinal pigment epithelium (RPE). At 1 week, images showed a progressive loss of the affected outer retinal layers, namely, the ONL and the outer plexiform layer. Concomitant distortion of the inner nuclear and plexiform layers generated a pattern of “archways” between adjacent laser spots. The photoreceptor layers (PRL) seemed to be eliminated in the photocoagulated area, particularly at the borders of each lesion. The lesion center contained a condensed RPE and PRL segment. The ONL recovered partially, but the PRL inner and outer segments remained absent. During the long-term follow-up, RPE cells migrated to the center of the lesion, forming a hyperplastic scar.Conclusions: The characteristic morphology of retinal photocoagulation effects in vivo and over time was identified for the first time in human eyes using SD-OCT. The OCT imaging demonstrated a well-defined reproducible area of destruction confined to the outer retinal layers. Healing proceeded as the condensation of the RPE and PRL in the lesion center.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Novel Therapy for Transthyretin–related Ocular Amyloidosis: A Pilot Study of Retinal Laser Photocoagulation

Takahiro Kawaji, Yukio Ando, Ryuhei Hara, Hidenobu Tanihara — 2010-01-04

Objective: The occurrence of ocular complications associated with transthyretin-related familial amyloidotic polyneuropathy increases with time, even after liver transplantation, which leads to a halt in the progression of systemic neurologic complications. This study investigated a new strategy to prevent ocular involvements.Design: Two interventional case reports.Participants: Two patients with familial amyloidotic polyneuropathy who had progressive ocular manifestations.Methods: We used panretinal laser photocoagulation, which damages the retinal pigment epithelium, the main location for synthesis of amyloidogenic transthyretin in ocular tissues, to treat 1 eye of each patient. After laser photocoagulation, we performed general ophthalmic examinations every 3 months for 3 years.Main Outcome Measures: Fundus photography, visual acuity, and intraocular pressure.Results: Panretinal laser photocoagulation clearly prevented progression of amyloid deposition in the vitreous and on the retinal surface in both cases during 3 years of follow-up. No serious complications occurred.Conclusions: Panretinal laser photocoagulation is a safe and well-known procedure that offers a new treatment option to mitigate ocular manifestations in patients with transthyretin-related familial amyloidotic polyneuropathy.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Acute Retinal Necrosis: The Effects of Intravitreal Foscarnet and Virus Type on Outcome

2009-12-22

Purpose: To study the effects of intravitreal foscarnet and the clinical differences between varicella zoster virus (VZV) and herpes simplex virus (HSV) induced acute retinal necrosis (ARN).Design: Retrospective comparative case series.Participants: Eighty-one eyes of 74 patients.Methods: A retrospective case note analysis was performed in 2 tertiary referral centers.Main Outcome Measures: Presenting and final visual acuity, and progression to retinal detachment.Results: Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity on presentation was similar (P = 0.48), but a larger proportion had better vision (≥20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater proportion of eyes with poor vision (≤20/200) was found at the 12-month follow-up in the VZV-ARN group (60%) compared with the HSV-ARN group (35%). A greater degree of visual loss in the VZV-ARN group (0.4 logarithm of the minimum angle of resolution [logMAR]) compared with the HSV-ARN group (0.04 logMAR) was detected (P = 0.016). Retinal detachment was 2.5-fold more common in VZV-ARN (62%) compared with HSV-ARN (24%). When comparing eyes treated with (n = 56) and without (n = 25) intravitreal foscarnet, there was a 40% lower rate in retinal detachment (53.6% vs 75.0%) for VZV-ARN (P = 0.23). The numbers with HSV-ARN were too small for analysis.Conclusions: The results support the difference of outcome in HSV-ARN and VZV-ARN. Therefore, viral identification serves as a key to predicting outcome in these patients. Intravitreal foscarnet seems to be a useful adjunct for the treatment of ARN in that it reduced rate of retinal detachment.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Nonaccidental Trauma and Peripheral Retinal Nonperfusion

2009-12-24

Purpose: To present fluorescein angiographic findings demonstrating retinal vascular alterations in children subjected to nonaccidental trauma (NAT).Design: Retrospective non-comparative consecutive case series.Participants: Ten eyes of 5 children with the diagnosis of NAT seen at William Beaumont Hospital between August 2007 and December 2008.Methods: We retrospectively reviewed the charts of 5 consecutive patients with NAT. All patients underwent detailed ophthalmic evaluation under anesthesia, fundus photography, and fluorescein angiography (FA).Main Outcome Measures: The primary outcome was FA findings demonstrating alterations in retinal vascular perfusion, retinal neovascularization, and traction retinal detachment.Results: Seven of 10 eyes demonstrated peripheral retinal nonperfusion by FA, with interruption of both the arterial- and venous-side of the retinal vascular tree. All of the eyes with retinal nonperfusion also presented with preretinal and/or vitreous hemorrhage; none of the eyes without ischemia demonstrated preretinal or vitreous blood. None of the children were born prematurely or had a medical or family history that could otherwise explain their findings. None of the eyes exhibited neovascularization or retinal detachment. Two eyes were treated with laser photocoagulation alone; 2 eyes were treated with vitrectomy alone owing to a nonclearing premacular hemorrhage; 2 eyes were treated with vitrectomy and laser photocoagulation; and 1 eye was observed without treatment.Conclusions: Peripheral retinal nonperfusion was noted by FA in 7 eyes of infants who were victims of nonaccidental head trauma. Preretinal and/or vitreous hemorrhage may be associated with the development of retinal nonperfusion. Physicians may consider FA in children with known or suspected NAT. The role of prophylactic laser treatment is unclear, and close observation for the development of neovascularization is warranted.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Evaluation of an Intravitreal Fluocinolone Acetonide Implant versus Standard Systemic Therapy in Noninfectious Posterior Uveitis

2010-01-15

Purpose: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU).Design: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial.Participants: Subjects with unilateral or bilateral NIPU.Methods: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (≥0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (≥0.1 mg/kg daily).Main Outcome Measures: Time to first recurrence of uveitis.Results: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P≤0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group.Conclusions: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Cyclosporine for Ocular Inflammatory Diseases

2009-12-24

Purpose: To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation.Design: Retrospective cohort study.Participants: A total of 373 patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007 inclusive.Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.Main Outcome Measures: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity.Results: Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of inflammation over at least 2 visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone ≤ 10 mg/day) was achieved by 22.1% by 6 months and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year by 10.7% of the population. Patients aged more than 55 years were more than 3-fold more likely to discontinue therapy because of toxicity than patients aged 18 to 39 years. Doses of 151 to 250 mg/day tended to be more successful than lower doses and were not associated with a higher discontinuation for toxicity rate; higher doses did not seem to offer a therapeutic advantage.Conclusions: Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was tolerated by the majority of patients, toxicity was more frequent with increasing age; alternative agents may be preferred for patients aged more than 55 years.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Cigarette Smoking as a Risk Factor for Uveitis

Phoebe Lin, Allison R. Loh, Todd P. Margolis, Nisha R. Acharya — 2009-12-24

Purpose: To determine the association between tobacco smoking history and uveitis.Design: Retrospective, case-control study.Participants: A total of 564 patients with ocular inflammation seen in the Proctor Foundation uveitis clinic between 2002 and 2009, and 564 randomly selected patients seen in the comprehensive eye clinic within the same time period.Methods: A retrospective medical record review of all cases and controls.Main Outcome Measures: A logistic regression analysis was conducted with ocular inflammation as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, race, and median income.Results: The odds of a smoker having ocular inflammation were 2.2-fold that of a patient who had never smoked (95% confidence interval [CI], 1.7–3.0; P<0.001). All anatomic subtypes of uveitis were associated with a positive smoking history, with odds ratios (ORs) of 1.7 (95% CI, 1.2–2.4; P = 0.002) for anterior uveitis, 2.7 (95% CI, 1.4–5.6; P = 0.005) for intermediate uveitis, 3.2 (95% CI, 1.3–7.9; P = 0.014) for posterior uveitis, and 3.9 (95% CI, 2.4–6.1; P<0.001) for panuveitis. In patients with panuveitis and cystoid macular edema (CME), the OR was 8.0 (95% CI, 3.3–19.5; P<0.001) compared with 3.1 (95% CI, 1.8–5.2; P<0.001) for patients without CME. Patients with intermediate uveitis and CME also had a higher OR (OR 8.4; 95% CI, 2.5–28.8; P = 0.001) compared with patients without CME (OR 1.5; 95% CI, 0.6–3.8; P = 0.342). Patients with a smoking history were at greater odds of having infectious uveitis (OR 4.5; 95% CI, 2.3–9.0; P<0.001) than noninfectious uveitis (OR 2.1; 95% CI, 1.6–2.8; P<0.001), although both were associated with smoking.Conclusions: A history of smoking is significantly associated with all anatomic subtypes of uveitis and infectious uveitis. The association was greater in patients with intermediate uveitis and panuveitis with CME compared with those without CME. In view of the known risks of smoking, these findings, if replicated, would give an additional reason to recommend smoking cessation in patients with uveitis.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease

2009-12-24

Purpose: To determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis.Design: Comparative case series.Participants: We included 1147 patients.Methods: All patients with bilateral ocular inflammatory disease presenting to any of 10 uveitis centers in the 3-month period between January 1 and March 31, 2006 (inclusive), were asked to participate. The clinical and historical features of disease were obtained from the participants via direct interview and chart review. Patients were stratified based on whether they were diagnosed with VKH disease or non-VKH uveitis for statistical analysis.Main Outcome Measures: Presence or absence of various clinical features in the 2 populations.Results: Of 1147 patients, 180 were diagnosed with VKH disease and 967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed with VKH than non-VKH disease compared with other ethnicities. In acute disease, the finding of exudative retinal detachment was most likely to be found in VKH disease with a positive predictive value (PPV) of 100 and negative predictive value (NPV) of 88.4, whereas in chronic disease, sunset glow fundus was most likely to be found, with a PPV of 94.5 and NPV of 89.2.Conclusions: Numerous clinical findings have been described in the past as important in the diagnosis of VKH. The current study reveals that of these, 2 are highly specific to this entity in an ethnically and geographically diverse group of patients with nontraumatic bilateral uveitis. These clinical findings are exudative retinal detachment during acute disease and sunset glow fundus during the chronic phase of the disease.Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references.

Orbital Cysticercosis: Clinical Manifestations, Diagnosis, Management, and Outcome

2010-01-08

Purpose: To describe the clinical manifestations, diagnosis, management, and outcome of orbital cysticercosis in a tertiary eye care center in Southern India.Design: Retrospective observational case series.Participants: A total of 171 patients with orbital cysticercosis.Methods: Retrospective case series involving consecutive patients with orbital cysticercosis from March 1990 to December 2001.Main Outcome Measures: Clinical resolution and significant residual deficit.Results: The median age at presentation was 13 years (range 2–65 years), and 93 patients (54.4%) were male. The 3 main symptoms at presentation were periocular swelling (38%), proptosis (24%), and ptosis (14%) with a median duration of 2 (range 0–24) months. The 3 main signs at presentation included ocular motility restriction (64.3%), proptosis (44.4%), and diplopia (36.8%). The cyst locations in the decreasing order of frequency were anterior orbit (69%), subconjunctival space (24.6%), posterior orbit (5.8%), and the eyelid (0.6%). In all, 80.7% of patients had cysts in relation to an extraocular muscle. The superior rectus (33.3%) was the most commonly involved extraocular muscle. Contact B-scan ultrasonography was diagnostic of cysticercosis in 84.4% of patients. Orbital cysticercosis was managed medically in 158 of 166 patients. Although 149 patients received a combination of oral albendazole and prednisolone, 1 patient received oral albendazole alone, 7 patients received oral prednisolone alone, and 1 patient received oral praziquantel. Surgery was performed in 8 patients. Clinical resolution was seen in 128 of 138 patients (92.8%) at 1 month and 81 of 85 patients (95.3%) at 3 months. A significant residual deficit was present in 29 of 138 patients (21.0%) at the final follow-up and included proptosis in 7 patients, ptosis in 6 patients, ocular motility restriction in 3 patients, diplopia in 2 patients, strabismus in 2 patients, and a combination of the above in 9 patients.Conclusions: Orbital cysticercosis is a common clinical condition in the developing world. It typically affects young individuals and has a wide spectrum of clinical manifestations. Both B-scan ultrasonography and computed tomography scan are useful in confirming the diagnosis. Despite resolution of cysticercosis with medical management, a significant proportion of patients may have residual functional deficits.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Primary Orbital Liposarcoma

2009-12-21

Purpose: To describe 6 new cases of primary orbital liposarcoma and provide a review of the relevant literature.Design: Noncomparative consecutive case series and literature review.Participants: Six patients with primary orbital liposarcoma.Methods: Review of patient charts, imaging, and histopathology; literature review.Main Outcome Measures: Patient demographics; clinical presentations; results of radiologic imaging; histopathology; surgical techniques used and their complications; other treatment modalities; outcomes and recurrences.Results: Six cases of primary orbital liposarcoma were identified, 5 of which were primary presentations and 1 of which was a recurrence. In 4 cases, exenteration was deferred, resulting in recurrence of disease in all 4. All cases were exenterated, and 2 cases had local recurrence despite exenteration. Two cases were associated with the Li-Fraumeni syndrome and other malignancies. Literature review identified 34 other cases of primary orbital liposarcoma, which, partly because of its rarity, is frequently initially misdiagnosed. The most common subtype is myxoid (56.8%); other types are pleomorphic (10.8%) and well differentiated (29.7%). Well-differentiated tumors have the best prognosis. Non-exenterating surgery was associated with recurrence, although recurrence post-exenteration also occurred. Although radiotherapy has an established role in the treatment of nonorbital liposarcoma, the role of both radiotherapy and chemotherapy in the management of primary orbital liposarcoma is still unclear.Conclusions: Orbital liposarcoma remains a diagnostic and surgical challenge. Exenteration remains the treatment of choice, but clinicians must also be aware that liposarcoma may herald the diagnosis of the Li-Fraumeni familial cancer syndrome.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Ocular and Orbital Manifestations of the Inherited Bone Marrow Failure Syndromes: Fanconi Anemia and Dyskeratosis Congenita

2009-12-21

Purpose: The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS). All 4 syndromes have been associated with various physical abnormalities. As part of a genotype/phenotype/cancer susceptibility study, we determined the prevalence of ophthalmic manifestations in these 4 syndromes.Design: Cross-sectional study of a patient cohort.Participants: Seventy-five patients with an IBMFS and 121 of their first-degree relatives were seen in the National Eye Institute, National Institutes of Health, from 2001 to 2007. The patient group included 22 with FA, 28 with DC, 19 with DBA, and 6 with SDS.Methods: Every participant underwent a complete ophthalmic evaluation and digital facial photography with an adhesive paper ruler on the patient's forehead for an internal measure of scale. Interpupillary distance (IPD), inner canthal distance (ICD), outer canthal distance (OCD), palpebral fissure length (PFL), and corneal diameter (CD) were measured. Thirteen of the 22 patients with FA underwent axial length (AL) measurements by A-scan ultrasonography.Main Outcome Measures: Type and prevalence of ophthalmic manifestations.Results: Ninety-five percent of patients with FA had at least 1 abnormal parameter, and 25% of patients had at least 4 abnormal parameters. Eighty-two percent of patients had small palpebral fissures, 69% of patients had simple microphthalmia, 64% of patients had small OCD, 55% of patients had microcornea, 28% of patients had ptosis, and 6% of patients had epicanthal folds. In patients with DC, abnormalities of the lacrimal drainage system (29%) were the most prevalent findings, followed by retinal abnormalities (pigmentary changes, retinal neovascularization, retinal detachment, exudative retinopathy) in 21%, cicatricial entropion with trichiasis and blepharitis in 7% each, and sparse eyelashes and congenital cataract in 3.5% each. No significant ophthalmic abnormalities were seen in patients with DBA or SDS.Conclusions: Syndrome-specific ocular findings are associated with FA and DC and may antedate diagnosis of the specific syndrome. Early recognition of these abnormalities is important for optimal management.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography

2009-12-24

Purpose: To investigate by optical coherence tomography (OCT) the topographic pattern and temporal sequence of fiber loss in the peripapillary retinal nerve fiber layer (RNFL) of patients with Leber's hereditary optic neuropathy (LHON) in a longitudinal follow-up.Design: Cohort study.Participants: Six eyes of 4 patients with molecularly defined LHON were enrolled before the subacute period of visual loss.Methods: Subjects were studied by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic stage of the disease. Examinations were carried out at 4 different time points: presymptomatic stage, time of visual loss, and 3 and 9 months later.Main Outcome Measures: Peripapillary RNFL thickness for each quadrant of the optic nerve. Statistical comparisons were performed by ordinary analysis of variance with Dunnett's post-test.Results: A significant increase of RNFL thickness was detected in the temporal and inferior quadrants between the presymptomatic stage and the disease onset (P<0.05). The 360-degree average and the superior and nasal quadrants showed a nonstatistically significant increase of thickness at this time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and inferior (P<0.01) quadrants, RNFL thickening showed statistically significant changes between the presymptomatic stage and the 3-month follow-up. At 3 months, a nonsignificant reduction of RNFL thickness was detected in the temporal quadrant. A significant reduction of RNFL was detected in all but the nasal quadrants between the presymptomatic stage and the 9-month Follow-up.Conclusions: The RNFL thickness increase first appeared at the temporal and inferior quadrants. Conversely, at 3 months the thickening fibers were more evident in the superior and nasal quadrants. These findings are consistent with the established preferential early involvement of the papillomacular bundle in LHON. We also demonstrated the previously unrecognized simultaneous early involvement of the inferior quadrant. The late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage that continues for 3 months and may represent a therapeutic window of opportunity.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Increased Tissue Endothelin-1 and Endothelin-B Receptor Expression in Temporal Arteries from Patients with Giant Cell Arteritis

Ivan Dimitrijevic, Christina Andersson, Pehr Rissler, Lars Edvinsson — 2009-12-24

Purpose: Endothelin (ET)-1 has been implicated in the atherosclerotic process and during inflammation. Similarity in the development process of giant cell arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have been developed, principally to target cardiovascular disease states. High doses of corticosteroids currently are used in the treatment of GCA, whereas other treatments are not as reliably effective. The present study was performed to elucidate the role for ET-1, ETA, and ETB receptors in GCA.Design: Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue.Participants: The study included 10 patients with GCA and 10 control patients with clinically suspected GCA but diagnosed not to have GCA.Methods: Immunohistochemistry, with anti ET-1, anti-ETA, and anti-ETB antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries.Main Outcome Measures: Endothelin-1, ETA, and ETB receptor immunostaining intensities were quantified.Results: Temporal arteries from the patients with GCA showed the typical histologic features, including intimal thickening, disruption or loss of the elastic lamina, and inflammatory infiltrates of lymphocytes, macrophages, and multinucleated giant cells. These features were associated with increased ET-1 and ETB receptor immunoreactivity in the medial layer of the temporal arteries and endothelial cells in patients with GCA compared with the controls. The increased ET-1 and ETB receptor immunoreactivity occurred in vascular smooth muscle cells (SMCs) and multinucleated giant cells. The ET-1 and ETB receptor immunoreactivity correlated with the degree of systemic inflammation. No changes were observed in ETA receptor expression in SMCs or endothelial cells compared with controls.Conclusions: The results suggest a role for ET-1 and ETB receptors in GCA. Inhibiting the ET system may provide a corticosteroid-sparing alternative in the treatment of GCA.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Merkel Cell Carcinoma of the Conjunctiva

Satoru Kase, Kan Ishijima, Susumu Ishida, Narsing A. Rao — 2010-03-01

Merkel cell carcinoma (MCC) is a rare, highly malignant tumor known to present with lymph node metastasis or local recurrence and satellite lesions. We herein report a patient with a novel finding of MCC of the eyelid that metastasized to the conjunctiva.

Freely Mobile Subconjunctival Cyst

Aaron Savar, Tanuj Nakra — 2010-03-01

A variety of cystic structures can appear on the ocular surface. These lesions are typically fixed to the tissue of origin. Conjunctival lesions are sometimes described as “freely” mobile with respect to the sclera, though the adjacent or overlying conjunctiva is firmly adherent. There have been several reports in the literature of mobile subconjunctival cysts that are not attached to surrounding tissues. This appears to be a rare phenomenon given the paucity of reports in the literature. We report such a case with photographic and video documentation and discuss the surgical management.

Quality of Life after Limbal Transplants

Ammar Miri, Manu Mathew, Harminder S. Dua — 2010-03-01

Moderate to severe limbal stem cell deficiency (LSCD) causes ocular discomfort and visual loss. Allo or auto limbal stem cell transplantation (LSCT) is required for ocular surface reconstruction (OSR). Often multiple interventions including other procedures such as buccal mucosal or amniotic membrane grafts are necessary. Various criteria have been attributed to define success or failure following OSR, but no study has thus far addressed the issue of visual function-related quality of life (QOL) in these difficult cases, although QOL related to other eye diseases and interventions has been reported. Herein we report the QOL assessment of patients who had undergone LSCT.

DSAEK Graft Evaluation Using C:P Ratio

George D. Kymionis, Georgios A. Kontadakis, Sonia H. Yoo — 2010-03-01

We read with interest the study by Scorcia et al that evaluates the change in posterior curvature of the cornea as a possible cause of the hyperopic shift observed after Descemet's stripping automated endothelial keratoplasty (DSAEK). The authors' results indicate that the shape of the donor graft, thinner in the center and thicker in the periphery, is the cause of the hyperopic shift due to the negative corneal power added in the posterior surface.

Author reply

2010-03-01

We thank Kymionis et al for their comments. We have also reviewed the previous study performed by Yoo et al who used the anterior segment optical coherence tomography (AS-OCT) to describe the Descemet's stripping with automated endothelial keratoplasty graft shape and to calculate an index (C:P ratio) to represent the thickness discrepancy between the center and the periphery. Although the AS-OCT is probably one of the most accurate tools to analyze the corneal layers there are some limits to this.

Normal-Tension Glaucoma or PVL?

Michael C. Brodsky — 2010-03-01

In their recent article, Leung et al analyzed a cohort of 286 patients with normal tension glaucoma and report silent cerebral infarcts on magnetic resonance imaging in 64 patients (22.4%). The most common sites for the observed silent infarct were the basal ganglia (48.4%) followed by the periventricular area (20.3%). One potential confounding variable in the latter group is prematurity, which is associated with periventricular leukomalacia (PVL) in up to 25% of cases.

Author reply

2010-03-01

We sincerely thank Dr. Brodsky for his interest in our article, and for sharing his expertise on periventricular leukomalacia (PVL) with us. In 1995, Jacobson et al recognized that PVL may produce a unique form of bilateral segmental optic nerve hypoplasia/congenital optic atrophy, characterized by abnormally large optic cup and a thin neuroretinal rim contained within a normal-sized optic disc. Brodsky proposed that the large optic cups can simulate glaucoma and a history of prematurity, normal intraocular pressure, and characteristic symmetrical inferior visual field defects serves to distinguish PVL from glaucomatous optic atrophy.

Foreign Body from an Eyeglass Screw

Ilia Piven, Guy Ben-Simon — 2010-03-01

We had the opportunity to remove a glasses screw from periorbital tissues during the operations of 2 trauma cases. To the best of our knowledge, there is no report in the literature describing a glasses screw that entered the periorbital tissues due to trauma. We performed an electronic search in MedLine and the Cochrane Library with zero results for any combinations of keywords “screw + glasses,” “screw + spectacles,” “screw + foreign body,” “screw + eye” related to the field of ophthalmology. It seems to be the first report in the literature that demonstrates that as a result of a face trauma, the glasses screw might penetrate the skin and remain in the body. We would be glad to receive additional messages about similar cases from readers.

OCT Interpretations

Pearse A. Keane, Narsing A. Rao, Srinivas R. Sadda — 2010-03-01

We read with interest the recent study by Ishihara et al describing the features of acute Vogt-Koyanagi-Harada (VKH) disease as imaged using spectral domain optical coherence tomography (OCT) with B-scan averaging. VKH disease is a diffuse granulomatous inflammatory disorder of the uvea that results in multifocal serous detachment of the retina. In their study, the authors hypothesize that the acute fluid exudation characteristic of the disease results in splitting of the photoreceptor outer and inner segments, with the formation of large intraretinal cystoid spaces. While this hypothesis is interesting, we disagree with the authors on their interpretation of the OCT findings. Furthermore, we do not believe that their hypothesis is consistent with the known clinical course, pathobiology, and histological features of this disorder.

Author reply

Kenji Ishihara, Masanori Hangai, Mihori Kita, Nagahisa Yoshimura — 2010-03-01

We thank Keane et al for their comments regarding the interpretation of speckle-noise-reduced spectral-domain optical coherence tomography (SD-OCT) features of eyes with acute Vogt-Koyanagi-Harada (VKH) disease. After considering the known clinical course, pathobiology, and histological features of VKH disease, they offer interesting comments about our interpretation of the OCT features. Because little histopathological information is available on acute VKH disease, its OCT features should be carefully interpreted after objectively analyzing its morphological characteristics.

Melanoma, Vitiligo, and Uveitis

Daniel M. Albert — 2010-03-01

Yea et al described a patient who underwent successful immunotherapy for metastatic cutaneous melanoma with autologous tumor-reactive tumor-infiltrating lymphocytes and developed ocular and systemic autoimmunity, including vitiligo and uveitis resembling Vogt-Koyanagi-Harada (VKH) Syndrome. The report provides clues into the pathogenesis of the VKH syndrome, and the authors' review of the recent literature is informative. A further review of earlier work, principally by Lerner et al, puts this article in better perspective for the clinical ophthalmologist with regard to the relationship of melanoma, vitiligo, uveitis, and VKH. Dr Lerner, the discoverer of melatonin and the founding chair of Yale's Department of Dermatology, spent 60 years studying vitiligo and convincingly demonstrated that vitiligo is a systemic, autoimmune disease affecting pigmented cells throughout the body rather than a purely cutaneous problem. The development of vitiligo can occur with both cutaneous and ocular melanoma and results in a more favorable course. Furthermore, there is a strong association between vitiligo and uveitis, and this appears to be most common in vitiligo associated with melanoma (19%). This is seen in nonmelanoma vitiligo patients as well. VKH appears to be at one end of the spectrum of vitiligo occurring in association with uveitis, and is uncommon, accounting for only 1%–5% of patients attending a vitiligo clinic. Patients with vitiligo have an increased incidence of more mild uveitis. Less severe ocular inflammation insufficient for the diagnosis of VKH has been reported in 5% of vitiligo patients. In addition, noninflammatory depigmented lesions of the ocular fundus are seen in 18%–31% of non-VKH vitiligo patients. Conversely, about 5% of patients with idiopathic uveitis not meeting clinical criteria for VKH have been observed to have some form of vitiligo.

Author reply

Steven Yeh, Steven A. Rosenberg, Robert B. Nussenblatt — 2010-03-01

We thank Dr. Albert for his comments and interest in our recent work describing the rare development of systemic and ocular autoimmunity following successful autologous, tumor-infiltrating lymphocyte (TIL) therapy for recurrent, metastatic melanoma that was refractory to a number of prior therapies. Our patient developed symptoms that mimicked the findings of Vogt-Koyanagi-Harada (VKH) syndrome and provided potential insight into the pathogenesis of VKH.

Lacrimal Canaliculus

Hirohiko Kakizaki, Ken Asamoto, Takashi Nakano, Dinesh Selva, Igal Leibovitch — 2010-03-01

There are only a few studies on the anatomy of the common lacrimal canaliculus (CLC) and its surrounding tissues. The CLC is thought to act as a valve, and the mechanism is functionally established by the movement of Horner's muscle and the tissues attached to the CLC, including the 2 lamellae medial canthal tendon situated in front of it. The aim of our study is to characterize the detailed microscopic anatomy of the CLC and the tissues adjacent to it. The term “CLC” is used to represent the part of the canaliculus not covered by Horner's muscle.

Past, Present, and Future of Ophthalmic Surgery

George Bohigian — 2010-03-01

The past, present, and future of ophthalmic surgery is found in both the Letter to the Editor by Harry H. Mark, MD, in “History of Ophthalmology” and the article “Robot-assisted vitreoretinal surgery: development of a prototype and feasibility studies in an animal model” by Taskashi Ueta, MD, et al in the August 2009 issue of Ophthalmology. Note there are innovative videos accompanying this article in the electronic edition. Great strides are being made in robot-assisted surgery such as fine computerized motor skills that dampens the surgeon's microtremors, enhanced 3-dimensional views, tactile feel, remote access, etc. How long will it be before cataract and retinal surgery may be done remotely? Presently we use computer models for training and assessing surgery in wet labs.

Ophthalmology

Editorial Board

This Issue At A Glance

Contents

A Tale of Two Systems: Health Reform in China and the United States

Prevalence of Vision Impairment in Older Adults in Rural China: The China Nine-Province Survey

Distribution of Axial Length and Ocular Biometry Measured Using Partial Coherence Laser Interferometry (IOL Master) in an Older White Population

Hormone Replacement Therapy in Relation to Risk of Cataract Extraction: A Prospective Study of Women

Limbal Stem Cell Deficiency after Topical Mitomycin C Therapy for Primary Acquired Melanosis with Atypia

Descemet's Stripping Automated Endothelial Keratoplasty Outcomes Compared with Penetrating Keratoplasty from the Cornea Donor Study

Detection of Bacterial Endosymbionts in Clinical Acanthamoeba Isolates

Screening for Glaucoma in High-Risk Populations Using Optical Coherence Tomography

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

Simvastatin and Disease Stabilization in Normal Tension Glaucoma: A Cohort Study

Chronic Kidney Disease and Intraocular Pressure: The Singapore Malay Eye Study

The Incidence of Retinal Vein Occlusion in the Ocular Hypertension Treatment Study

Natural History of Drusenoid Pigment Epithelial Detachment in Age-Related Macular Degeneration: Age-Related Eye Disease Study Report No. 28

The Complement Component 5 Gene and Age-Related Macular Degeneration

Severe Intraocular Inflammation after Intravitreal Injection of Bevacizumab

Impact of Coagulation-Balance Gene Predictors on Efficacy of Photodynamic Therapy for Choroidal Neovascularization in Pathologic Myopia

Are Myopic Eyes Less Likely to Have Diabetic Retinopathy?

Retinopathy in Persons without Diabetes: The Handan Eye Study

In Vivo Retinal Morphology after Grid Laser Treatment in Diabetic Macular Edema

High-Resolution Imaging of the Human Retina In Vivo after Scatter Photocoagulation Treatment Using a Semiautomated Laser System

Novel Therapy for Transthyretin–related Ocular Amyloidosis: A Pilot Study of Retinal Laser Photocoagulation

Acute Retinal Necrosis: The Effects of Intravitreal Foscarnet and Virus Type on Outcome

Nonaccidental Trauma and Peripheral Retinal Nonperfusion

Evaluation of an Intravitreal Fluocinolone Acetonide Implant versus Standard Systemic Therapy in Noninfectious Posterior Uveitis

Cyclosporine for Ocular Inflammatory Diseases

Cigarette Smoking as a Risk Factor for Uveitis

Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease

Orbital Cysticercosis: Clinical Manifestations, Diagnosis, Management, and Outcome

Primary Orbital Liposarcoma

Ocular and Orbital Manifestations of the Inherited Bone Marrow Failure Syndromes: Fanconi Anemia and Dyskeratosis Congenita

Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography

Increased Tissue Endothelin-1 and Endothelin-B Receptor Expression in Temporal Arteries from Patients with Giant Cell Arteritis

Merkel Cell Carcinoma of the Conjunctiva

Freely Mobile Subconjunctival Cyst

Quality of Life after Limbal Transplants

DSAEK Graft Evaluation Using C:P Ratio

Author reply

Normal-Tension Glaucoma or PVL?

Author reply

Foreign Body from an Eyeglass Screw

OCT Interpretations

Author reply

Melanoma, Vitiligo, and Uveitis

Author reply

Lacrimal Canaliculus

Past, Present, and Future of Ophthalmic Surgery