Ophthalmology

Demographics, Etiology, and Behavior of Conjunctival Squamous Cell Carcinoma in the 21st Century

Zeynel A. Karcioglu, Michael D. Wagoner — 2009-11-01

The cancer of the squamous epithelium was labeled as “epithelioma” by Rudolph Virchow in the 1850s, but over the course of a century, its name gradually changed to squamous cell carcinoma (SCC). Although ophthalmologists deal with many primary, secondary, and metastatic forms of SCC in the eye and ocular adnexae, they tend to consider SCC arising in the conjunctiva as their “own” disease and typically assume responsibility for diagnosis and management of this disorder. Between the turn of the 20th century and the mid-1960s, this lesion underwent an identity crisis in which it was given many different names, including “leukoplakia,” “limbal epithelioma,” “dyskeratosis,” “dysplasia,” “pre-cancerous and cancerous hyperplasia,” and “Bowen's disease,” among others. In due course, this entity assumed the names it carries today: conjunctival squamous cell carcinoma (CSCC) or ocular surface squamous neoplasia (OSSN) which is considered “in situ” if it is restricted within the epithelium, and “invasive” if it is infiltrating beyond the confines of the epithelial basement membrane.

Complete Local Elimination of Infectious Trachoma from Severely Affected Communities after Six Biannual Mass Azithromycin Distributions

2009-09-10

Objective: To determine whether infectious trachoma can be completely eliminated from severely affected villages.Design: Cross-sectional survey of 2 villages previously enrolled and monitored over 42 months as part of a larger, group-randomized clinical trial.Participants: A total of 758 individuals residing in 2 villages with high baseline trachoma prevalence, of a total population of 768 (98.7%).Methods: All members of the 2 villages were offered 6 biannual mass treatments with oral azithromycin. At 42 months, each current village member was examined. The right upper tarsal conjunctiva was everted and swabbed. Samples were processed for evidence of Chlamydia trachomatis RNA.Main Outcome Measures: Clinical activity by World Health Organization simplified grading scale for trachoma and laboratory evidence of chlamydial RNA.Results: Average antibiotic coverage over the study period was 90% and 94% in the 2 villages. Clinical trachoma activity in children aged 1 to 5 years decreased from 78% and 83% in the 2 villages before treatment to 17% and 24% at 42 months. Polymerase chain reaction (PCR) evidence of infection in the same age group decreased from 48% to 0% in both villages at 42 months. When all age groups were examined, there were zero cases with evidence of chlamydial RNA among 758 total villagers tested.Conclusions: Biannual mass distribution of azithromycin can locally eliminate ocular chlamydial infection from severely affected communities.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ocular Manifestation in Treated Multibacillary Hansen's Disease

Rajul Parikh, Saju Thomas, Jayaprakash Muliyil, Shefali Parikh, Ravi Thomas — 2009-09-22

Purpose: To report the prevalence of ocular morbidity in patients with treated multibacillary Hansen's disease (HD) using modern ophthalmic diagnostic techniques in a rural community endemic for HD.Design: Cross-sectional, observation study.Participants: All patients with multibacillary HD who had completed their multidrug therapy and who resided in 4 defined geographical areas in Vellore, Tamil Nadu, India.Methods: All participants underwent a complete eye examination that included slit-lamp examination, esthesiometry, gonioscopy, applanation tonometry, and dilated fundus examination, including a stereobiomicroscopic examination of the fundus at an ophthalmic center set up for that purpose. Glaucoma suspects underwent automated perimetry using a Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA).Main Outcome Measures: The prevalence of various ocular disease parameters were reported as mean value with 95% confidence interval. The difference of disease prevalence between various leprosy groups was compared using an unpaired t test. The association between eye symptoms and potentially sight-threatening complications was analyzed using the chi-square test.Results: Three hundred eighty-six of the 446 patients with multibacillary HD residing in the defined areas were evaluated. Four patients (1.04%; 95% confidence interval [CI], 0.0%–2.0%) were bilaterally blind; 33 (8.55%; 95% CI, 5.8%–11.3%) had unilateral blindness. Mean intraocular pressure was 12 mmHg (standard deviation, 4.1 mmHg), and prevalence of glaucoma was 3.6% (95% CI, 1.8%–5.5%). Potentially sight-threatening (PST) pathologic features (corneal anesthesia, lagophthalmos, uveitis, scleritis, and advanced glaucoma) were present in 10.4% (95% CI, 7.4%–13.4%) of patients. Significant cataracts occurred 3 times more frequently in those with polar lepromatous leprosy. The odds ratio for PST pathology in the presence of patient-reported symptoms (pain, redness, inability to close eye, burning, and irritation) was 2.9 (95% CI, 1.34–6.26).Conclusions: Patients who have completed treatment for multibacillary HD continue to have significant ocular morbidity. A history of specific eye symptoms can be the basis for referral by field staff.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Proposed Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction

2009-09-10

Purpose: To compare clinical findings between patients with obstructive meibomian gland dysfunction (MGD) and normal controls and to propose diagnostic criteria for obstructive MGD.Design: Cross-sectional, observational case series.Participants: Fifty-three eyes of 53 patients (18 men, 35 women; age [mean ± standard deviation] 71.4 ± 10.0 years) who were diagnosed with obstructive MGD and 60 eyes of 60 healthy volunteers (22 men, 38 women; 71.0 ± 9.3 years) as a control group.Methods: Ocular symptoms were scored from 0 to 14 according to the number of existing symptoms. Lid margin abnormality was scored from 0 to 4 depending on the number of existing abnormalities. Meibomian gland changes were scored from 0 to 6 based on noncontact meibography (meibo-score). Superficial punctuate keratopathy (SPK) was scored from 0 to 3. Meibum was graded from 0 to 3 depending on the volume and quality. Tear film production was evaluated by Schirmer's test. Receiver operating characteristic curves with calculations of area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate obstructive MGD from normal eyes.Main Outcome Measures: Ocular symptom score, lid margin abnormality score, meibo-score, meibum score, SPK score, tear film breakup time (BUT), and the Schirmer value.Results: Ocular symptom score, lid margin abnormality score, meibo-score, meibum score, and SPK score were significantly higher in the obstructive MGD group than in the control group (P<0.0001 for all scores). The BUT was significantly shorter in the obstructive MGD group than in the control group (P<0.0001). The AUC values indicated that the ocular symptom score had the highest diagnostic power as a single parameter, followed by the lid margin abnormality score, meibo-score, and BUT.Conclusions: Based on these findings, we recommend that physicians use the ocular symptom score, lid margin abnormality score, and meibo-score to diagnose MGD. Obstructive MGD should be suspected when any 2 of the 3 scores are abnormal. Obstructive MGD is very likely when all 3 scores are abnormal.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Average 3-Dimensional Models for the Comparison of Orbscan II and Pentacam Pachymetry Maps in Normal Corneas

2009-09-10

Purpose: To assess the reliability of Orbscan (Bausch & Lomb, Salt Lake City, UT) and Pentacam (Oculus, Wetzlar, Germany) central corneal thickness (CCT) and peripheral corneal thickness (PCT) measurements based on 2 methodologies.Design: Evaluation of a diagnostic technology.Participants: Thirty healthy volunteers were recruited prospectively at the Department of Ophthalmology of the Hôtel-Dieu Hospital, Paris, France.Methods: Central corneal thickness and PCT were assessed, using ultrasound pachymetry (USP) as the gold standard. Two methodologies were used: (1) the traditional analysis of pachymetry data from 1 central and 8 peripheral reference positions on the cornea, and (2) a 3-dimensional (3-D) analysis based on average corneal pachymetry maps constructed for each system (Orbscan, Pentacam, and USP), each operator (operators 1 and 2), and each visit (visits A and B).Main Outcome Measures: Repeatability, intersystem reproducibility, interoperator reproducibility, reproducibility over time, and accuracy of Orbscan and Pentacam CCT and PCT measurements. Distribution and statistical significance of the differences between 3-D average maps.Results: Repeatability (Orbscan intraclass correlation coefficients [ICCs], 0.967–0.992; Pentacam ICCs, 0.986–0.997), interoperator reproducibility, and reproducibility over time (ICCs, 0.976–0.997) were excellent to almost perfect for both systems. Intersystem agreement was almost perfect for CCT (ICC, 0.980), but less strong for PCT (ICCs, 0.928–0.979). Despite a good to excellent agreement between the optical systems and USP (ICCs, 0.608–0.958), USP CCT readings were thicker (mean difference, up to 15.2 μm; P<0.05), and USP PCT readings were thinner (P<0.05). Orbscan and Pentacam average maps allowed comprehensive interpretation of differences between populations according to the magnitude, distribution, and statistical significance, minimizing the risk of giving excessive weight to few data measured at specific locations on the cornea.Conclusions: Both methodologies showed that Orbscan and Pentacam CCT readings are interchangeable, whereas caution should be used for PCT readings. Interchangeability with USP measurements also was shown to be limited. The high repeatability, interoperator reproducibility, reproducibility over time, the extent of the information generated by a single capture, and the noncontact nature of the Orbscan and Pentacam all suggest that optical systems eventually may replace USP as the gold standard for corneal pachymetry.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Characteristics of Traumatic Globe Rupture after Keratoplasty

2009-09-22

Objective: To analyze risk factors of traumatic wound rupture after penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK).Design: Retrospective case series.Participants: A total of 1962 consecutive cases were included.Methods: A review of consecutive patients undergoing either PKP (1776 eyes) or DALK (186 eyes) at 1 regional center between 1998 and 2006 was carried out to determine the incidence of traumatic globe rupture after keratoplasty. Ophthalmic and demographic factors were analyzed. A comparison with previous literature was performed.Main Outcome and Measures: Incidence, causes, and final visual acuity.Results: Of 43 eyes with globe rupture during this period, 36 received keratoplasty during this study period. The incidence of globe rupture after keratoplasty was 1.8% (36/1962). These 36 cases consisted of 35 of the 1776 eyes receiving PKP (2.0%) and 1 of the 186 eyes receiving DALK (0.5%). Globe rupture occurred 61.6±50.0 months (mean ± standard deviation) after keratoplasty in 43 cases. The major cause of trauma was a fall in elderly patients (73.2±8.4 years, 17 eyes), with lens damage occurring in all such cases. Although 15 eyes (34.9%) had a visual acuity of 20/200 or better at final follow-up, eyes showing lens damage were associated with poorer visual acuity than eyes with no lens damage (P<0.01).Conclusions: Wound weakness persisted for a long period after keratoplasty. A fall was observed frequently in elderly patients and resulted in poor visual outcome. Globe rupture associated with lens injury could be the predictor for future visual outcome.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Endothelial Involvement in Herpes Simplex Virus Keratitis: An In Vivo Confocal Microscopy Study

Toine Hillenaar, Christien Weenen, René J. Wubbels, Lies Remeijer — 2009-09-10

Purpose: To describe the appearance, frequency, and clinical consequences of corneal endothelial involvement in human herpes simplex virus (HSV) keratitis as seen by in vivo confocal microscopy (IVCM).Design: Prospective observational case series.Participants: A total of 285 patients with HSV keratitis who visited the cornea department of the Rotterdam Eye Hospital between May 2005 and May 2008. The control groups comprised the unaffected fellow eyes of patients with HSV keratitis, the eyes of 58 healthy volunteers, and the affected eyes of 62 patients with inflammatory corneal disorders other than HSV.Methods: We examined the eyes of all participants by IVCM and slit-lamp examination. For IVCM, corneas were scanned with Confoscan 3 or 4 (Nidek Technologies, Albignasego, Padova, Italy).Main Outcome Measures: All IVCM examinations were qualitatively reviewed for signs of endothelial deviations characteristic of endotheliitis. Endothelial cell density (ECD) was evaluated on the first and last visits of patients who were followed for more than 100 days. The differences in ECDs were calculated and converted to percent ECD change per year.Results: Endothelial alterations characteristic of endotheliitis were detected by IVCM in 107 of 250 patients with HSV keratitis (43%). These deviations consisted of pseudoguttata, enlarged intercellular gaps, infiltration of inflammatory cells into the endothelial layer, loss of defined cell boundaries, spot-like holes, and endothelial denudation. All of these signs disappeared with appropriate antiviral and anti-inflammatory treatment. However, the endothelium in eyes with endotheliitis-characteristic alterations showed a significant decrease in ECD (10.3% per year) compared with healthy fellow eyes.Conclusions: IVCM allows earlier detection of endothelial alterations in patients with HSV keratitis compared with slit-lamp examination. Although endotheliitis-specific alterations appear to resolve, the corneal endothelium can become irreversibly damaged.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison and Evaluation of Ocular Biometry Using a New Noncontact Optical Low-Coherence Reflectometer

2009-09-10

Purpose: To evaluate a new high-resolution noncontact biometer (Lenstar; Haag-Streit AG, Koeniz, Switzerland) using optical low-coherence reflectometry and to compare the clinical measurements with those obtained from the IOLMaster (Carl Zeiss, Jena, Germany) and the Pachμmeter (Haag-Streit AG).Design: Exploratory evaluation of diagnostic technology and nonrandomized, prospective clinical trial.Participants: Eighty subjects (144 eyes) aged 20 to 90 years with cataractous, pseudophakic, aphakic, silicon oil–filled, or normal eyes.Methods: Measurements of axial length (AL), anterior chamber depth (ACD), central corneal thickness (CCT), corneal radius (R1 [flattest radius of corneal curvature] and R2 [steep radius, 90° apart from R1]), and axis of the flattest radius (Ax1) obtained with the Lenstar were compared with those obtained with the IOLMaster or Pachμmeter. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t test, and its correlation was evaluated by Pearson coefficient.Main Outcome Measures: Axial length, CCT, ACD, R1, R2, and Ax1.Results: The overall mean AL measured with the Lenstar and the IOLMaster was 24.1 mm (r = 0.999). Anterior chamber depth was 3.19 mm (Lenstar) and 3.17 mm (IOLMaster; r = 0.875). Excellent correlations also were found for the corneal radius and the axis of flattest radius (R1, r = 0.927; R2, r = 0.929; and Ax1, r = 0.938). Mean CCT was 0.557 mm (r = 0.978) for both Lenstar and Pachμmeter.Conclusions: Measurements with the new Lenstar correlated well with those with the IOLMaster and Pachμmeter in cataractous, pseudophakic, aphakic, silicon oil–filled, and normal eyes. It is an accurate, fast instrument that provides additional information of interest to any cataract or refractive surgeon.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Visual Acuity Outcomes after Cataract Surgery in Patients with Age-Related Macular Degeneration: Age-Related Eye Disease Study Report No. 27

2009-08-24

Objective: To evaluate visual acuity outcomes after cataract surgery in patients with varying degrees of age-related macular degeneration (AMD).Design: Cohort study.Participants: A total of 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), a prospective, multicenter, epidemiological study of the clinical course of cataract and AMD and a randomized controlled trial of antioxidants and minerals.Methods: Standardized lens and fundus photographs, performed at baseline and annual visits, were graded by a centralized reading center using standardized protocols for severity of AMD and lens opacities. History of cataract surgery was obtained every 6 months. Analyses were conducted using multivariate logistic regression.Main Outcome Measure: The change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA.Results: Visual acuity results were analyzed for 1939 eyes that had cataract surgery during AREDS. The mean time from cataract surgery to measurement of postoperative BCVA was 6.9 months. After adjustment for age at surgery, gender, type, and severity of cataract, the mean change in visual acuity at the next study visit after the cataract surgery was as follows: Eyes without AMD gained 8.4 letters of acuity (P<0.0001), eyes with mild AMD gained 6.1 letters of visual acuity (P<0.0001), eyes with moderate AMD gained 3.9 letters (P<0.0001), and eyes with advanced AMD gained 1.9 letters (P = 0.04). The statistically significant gain in visual acuity after cataract surgery was maintained an average of 1.4 years after cataract surgery.Conclusions: On average, participants with varying severity of AMD benefited from cataract surgery with an increase in visual acuity postoperatively. This average gain in visual acuity persisted for at least 18 months.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Variable Expressivity and High Penetrance of CYP1B1 Mutations Associated with Primary Congenital Glaucoma

2009-09-10

Objective: To investigate penetrance and expressivity of CYP1B1 genotypes associated with primary congenital glaucoma (PCG).Design: Observational case series, systematic review, and comparative analysis of the literature.Participants: Forty probands affected with PCG, 16 siblings affected with PCG, and 103 siblings and 75 parents of the probands reported not to be affected by history. The participants were members of 40 unrelated families.Methods: Mutations were screened by restriction fragment length polymorphism, allele-specific polymerase chain reaction amplification, and direct sequencing. Ophthalmologic examination included slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, gonioscopy, and high magnification stereoscopic fundus examination, followed by standard achromatic perimetry.Main Outcome Measures: Identification of subjects carrying CYP1B1 mutations. Glaucoma diagnosis based on slit-lamp examination, IOP measurement, gonioscopic findings, optic nerve appearance, and perimetry.Results: Fifteen different homozygous or compound heterozygous mutant CYP1B1 genotypes were identified. Most probands and previously diagnosed subjects harbored G61E, R368H, R390H, and R469W mutations. Among the 178 apparently unaffected family members, 20 subjects from 12 families were observed to harbor 2 CYP1B1 mutations, suggesting an average penetrance of 73% for all the mutations. These 20 subjects ranged in age from 14 to 54 years. R390H appeared to have a notably high penetrance. Penetrance was 50% in the subset of families with incomplete penetrance. Ophthalmologic examination on 14 of the 20 apparently nonpenetrant individuals showed that 8 subjects were affected with juvenile open-angle glaucoma (JOAG) or primary open-angle glaucoma (POAG), and that 3 subjects were glaucoma suspect. One of the individuals with a JOAG diagnosis was the identical twin sibling of a proband affected with PCG.Conclusions: At least 57% of the PCG nonpenetrant individuals examined clinically were affected with JOAG or POAG to varying degrees, and overall penetrance of “affected CYP1B1 genotypes” with respect to glaucoma may be more than 90%. These findings suggest that “affected CYP1B1 genotypes” exhibit variable expressivity rather than nonpenetrance. The clinical implication of this observation is that seemingly unaffected relatives of patients with PCG, particularly those known to harbor CYP1B1 mutations, should undergo regular ophthalmologic examination to allow early diagnosis.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Incidence and Rates of Visual Field Progression after Longitudinally Measured Optic Disc Change in Glaucoma

Balwantray C. Chauhan, Marcelo T. Nicolela, Paul H. Artes — 2009-06-04

Objective: To determine whether glaucoma patients with progressive optic disc change have subsequent visual field progression earlier and at a faster rate compared with those without disc change.Design: Prospective, longitudinal, cohort study.Participants and Controls: Eighty-one patients with open-angle glaucoma.Methods: Patients underwent confocal scanning laser tomography and standard automated perimetry every 6 months. The complete follow-up was divided into initial and subsequent periods. Two initial periods—first 3 years (Protocol A) and first half of the total follow-up (Protocol B)—were used, with the respective remainder being the subsequent follow-up. Disc change during the initial follow-up was determined with liberal, moderate, or conservative criteria of the Topographic Change Analysis. Subsequent field progression was determined with significant pattern deviation change in ≥3 locations (criterion used in the Early Manifest Glaucoma Trial). As a control analysis, field change during the initial follow-up was determined with significant pattern deviation change in ≥1, ≥2, or ≥3 locations.Main Outcome Measures: Survival time to subsequent field progression, rates of mean deviation (MD) change, and positive and negative likelihood ratios.Results: The median (interquartile range) total follow-up was 11.0 (8.0–12.0) years with 22 (18–24) examinations. More patients had disc changes during the initial follow-up compared with field changes. The mean time to field progression was consistently shorter (protocol A, 0.8–1.7 years; protocol B, 0.3–0.7 years) in patients with prior disc change. In the control analysis, patients with prior field change had statistically earlier subsequent field progression (protocol A, 2.9–3.0 years; protocol B, 0.7–0.9). Similarly, patients with either prior disc or field change always had worse mean rates of subsequent MD change, although the distributions overlapped widely. Patients with subsequent field progression were up to 3 times more likely to have prior disc change compared with those without, and up to 5 times more likely to have prior field change compared with those without.Conclusions: Longitudinally measured optic disc change is predictive of subsequent visual field progression and may be an efficacious end point for functional outcomes in clinical studies and trials in glaucoma.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Refractive Errors in a Rural Chinese Adult Population: The Handan Eye Study

2009-09-10

Purpose: To describe the prevalence of and risk factors for myopia and other refractive errors in a rural, adult, Chinese population.Design: Population-based, cross-sectional study.Participants: A clustered, random sampling procedure was used to select 7557 Chinese people aged ≥30 years from Handan, China.Methods: All eligible subjects were invited to undergo a comprehensive eye examination, including standardized refraction. Myopia, high myopia, and hyperopia were defined as a spherical equivalent (SE) in the right eye of more than −0.5 diopter (D), less than −5.0 D, and 0.5 D or more, respectively. Astigmatism was less than −0.5 D of cylinder. Anisometropia was defined as a difference in SE of >1.0 D between the 2 eyes. Only phakic eyes were analyzed.Main Outcome Measures: Myopia and other refractive errors.Results: We included 6491 (85.9% participation rate) eligible subjects in this study. Adjusted to the 2000 China population census, the prevalence rate of myopia was 26.7% (95% confidence interval [CI], 25.6–27.8), hyperopia 15.9 % (95% CI, 15.0–16.8), astigmatism 24.5% (95% CI, 23.5–25.5), and anisometropia 7.7% (95% CI, 7.0–8.4). The prevalence of high myopia was 1.8% (95% CI, 1.5–2.1). Using a multivariate regression model, current smoking (odds ratio [OR], 0.7, 95% CI, 0.5–0.9), hours of reading (OR, 1.2; 95% CI, 1.1–1.4), diabetes (OR, 8.4; 95% CI, 2.2–32.5), and number of family members with myopia (OR, 1.3; 95% CI, 1.1–1.7, for each family member) were associated with myopia in younger persons (30–49 years). High school or higher education (OR, 1.8; 95% CI, 1.1–3.1), diabetes (OR, 1.6; 95% CI, 1.2–2.7), nuclear opacity (OR, 1.7; 95% CI, 1.2–2.3), and number of family members with myopia (OR, 1.5; 95% CI, 1.2–1.9) were risk factors in persons ≥50 years of age.Conclusions: Myopia affects more than one quarter of rural Chinese persons ≥30 years of age. Myopia is more common in younger people and is associated with different risk factors than in older people.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Prevalence of Amblyopia and Strabismus in White and African American Children Aged 6 through 71 Months: The Baltimore Pediatric Eye Disease Study

2009-09-16

Objective: To determine the age-specific prevalence of strabismus in white and African American children aged 6 through 71 months and of amblyopia in white and African American children aged 30 through 71 months.Design: Cross-sectional, population-based study.Participants: White and African American children aged 6 through 71 months in Baltimore, MD, United States. Among 4132 children identified, 3990 eligible children (97%) were enrolled and 2546 children (62%) were examined.Methods: Parents or guardians of eligible participants underwent an in-home interview and were scheduled for a detailed eye examination, including optotype visual acuity and measurement of ocular deviations. Strabismus was defined as a heterotropia at near or distance fixation. Amblyopia was assessed in those children aged 30 through 71 months who were able to perform optotype testing at 3 meters.Main Outcome Measures: The proportions of children aged 6 through 71 months with strabismus and of children aged 30 through 71 months with amblyopia.Results: Manifest strabismus was found in 3.3% of white and 2.1% of African American children (relative prevalence [RP], 1.61; 95% confidence interval [CI], 0.97–2.66). Esotropia and exotropia each accounted for close to half of all strabismus in both groups. Only 1 case of strabismus was found among 84 white children 6 through 11 months of age. Rates were higher in children 60 through 71 months of age (5.8% for whites and 2.9% for African Americans [RP, 2.05; 95% CI, 0.79–5.27]). Amblyopia was present in 12 (1.8%) white and 7 (0.8%) African American children (RP, 2.23; 95% CI, 0.88–5.62). Only 1 child had bilateral amblyopia.Conclusions: Manifest strabismus affected 1 in 30 white and 1 in 47 African American preschool-aged children. The prevalence of amblyopia was <2% in both whites and African Americans. National population projections suggest that there are approximately 677 000 cases of manifest strabismus among children 6 through 71 months of age and 271 000 cases of amblyopia among children 30 through 71 months of age in the United States.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Nine-Year Incidence and Risk Factors for Age-Related Macular Degeneration in a Defined Japanese Population: The Hisayama Study

2009-09-10

Purpose: To estimate the 9-year incidence and risk factors for age-related macular degeneration (AMD) in a general Japanese population.Design: Population-based, cohort study.Participants: In 1998, a total of 1775 Hisayama residents aged ≥40 years underwent a baseline eye examination. Of those, 1401 subjects (78.9%) took part in the follow-up eye examination in 2007 and were enrolled in the present study.Methods: At both time points, the characteristics of AMD were determined by grading color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System.Main Outcome Measures: Incident early and late AMD.Results: The age-standardized, 9-year cumulative incidence of early AMD was 10.0%, and that of late AMD was 1.4%. Men were found to have a significantly higher incidence of late AMD than women (age-adjusted odds ratio [OR], 2.97; 95% confidence interval [CI], 1.25–7.09). The incidence of both early and late AMD increased significantly with age. Multiple logistic regression analysis showed that older age (per 1 year; OR, 1.10; 95% CI, 1.05–1.16), smoking habits (OR, 3.98; 95% CI, 1.07–14.7), and higher circulating white blood cell (WBC) count (per 1000 cells/mm3) (OR, 1.38; 95% CI, 1.07–1.79) were significantly associated with the development of late AMD.Conclusions: Our findings suggest that the 9-year incidences of late AMD are lower among the Japanese than among white people in Western countries, and it is higher than among black people. Smoking habits and higher circulating WBC count are significant risk factors for the development of late AMD in the Japanese.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration

2009-08-24

Purpose: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD).Design: Dose-escalation, multicenter, interventional clinical trial.Participants: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions ≤12 disc areas in size and ≥50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) ≤20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye.Methods: Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks.Main Outcome Measure: Safety assessments.Results: There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 μm at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of ≥3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV.Conclusions: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Photodynamic Therapy and Intravitreal Triamcinolone for Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial

David Maberley, Canadian Retinal Trials Group — 2009-09-14

Purpose: To evaluate the efficacy of intravitreal triamcinolone acetonide (ITA) as an adjunct to photodynamic therapy with verteprofin (VPDT) in the treatment of predominantly classic, subfoveal choroidal neovascularization (CNV) owing to age-related macular degeneration (AMD).Design: A multicenter, 2-year, double-blind, randomized, sham-controlled trial conducted at 11 sites in Canada.Participants and Controls: One hundred individuals over the age of 50 were randomized 1:1 to either to VPDT alone or combined VPDT and ITA.Intervention: Participants all received full-fluence VPDT and were randomly assigned to either (1) a same-day injection of 4 mg ITA or (2) a sham intraocular injection.Main Outcome Measure: The primary end point was the change in numbers of letters read between baseline and 1 year.Results: Combination therapy with VPDT and ITA when compared with VPDT therapy alone resulted in no significant difference in final visual acuity at 1 year. Eyes treated with combination therapy lost an average of 17 letters compared with 20 letters for the VPDT group. Subjects receiving ITA required significantly fewer retreatments over the course of the study (1.28 vs 1.94, respectively; P = 0.003). Although elevated intraocular pressures were noted in a larger proportion of subjects receiving ITA, all of these individuals were managed successfully with topical ocular antihypertensive agents.Conclusions: There was no visual benefit to the addition of intravitreal triamcinolone to VPDT. Combination therapy, however, can reduce the number of VPDT treatments required by subjects who have predominantly classic CNV owing to AMD. This reduced treatment quantity needs to be weighed against potential side effects. (ClinicalTrials.gov number, NCT00148551).Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Monitoring Ocular Drug Therapy by Analysis of Aqueous Samples

2009-08-24

Objective: To assess the value of sampling aqueous humor for measurement of potential molecular targets and for pharmacokinetic analysis.Design: Substudy within the context of clinical trials.Participants: Forty patients with macular edema caused by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO), 11 patients with diabetic macular edema (DME), and 8 patients with neovascular age-related macular degeneration (NVAMD).Methods: Assays for potential molecular targets were performed on aqueous samples from patients participating in drug studies (CRVO, BRVO, and DME) or patients receiving standard care (NVAMD). Ranibizumab levels were measured in patients with CRVO or BRVO after the first and second injections of ranibizumab.Main Outcome Measures: Aqueous levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and ranibizumab.Results: Aqueous levels of VEGF were significantly higher in patients with DME than in patients with CRVO, which were significantly higher than those in patients with BRVO. Patients with NVAMD had aqueous VEGF levels in an intermediate range, significantly higher than those in patients with BRVO. One month after the second injection of ranibizumab, 27 of 39 patients with vein occlusions had no residual edema; mean aqueous levels of IL-6, IL-1β, and TNF-α were not greater in patients with residual edema; this provides a blueprint for definitive studies with larger cohorts. There was no significant difference in aqueous ranibizumab levels 1 month after the first injection of 0.5 mg versus injection of 0.3 mg, but 1 month after the second injection ranibizumab levels were significantly higher in eyes injected with 0.5 mg. There were substantial differences in levels among patients, but levels in the same patient at months 1 and 2 were highly correlated. No significant difference in aqueous ranibizumab levels was detected between phakic and pseudophakic patients who received the same dose.Conclusions: These data suggest that aqueous samples are useful for investigating potential involvement of molecular targets in various disease processes and for pharmacokinetic or pharmacodynamic studies.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Simultaneous Analyses of Vitreous Levels of 27 Cytokines in Eyes with Retinopathy of Prematurity

Tatsuhiko Sato, Shunji Kusaka, Hiroshi Shimojo, Takashi Fujikado — 2009-08-24

Purpose: To determine the vitreous levels of 27 types of cytokines in eyes with retinopathy of prematurity (ROP).Design: Retrospective case-control study.Participants: Twenty-seven eyes of 19 infants with stage 4 ROP were studied. Six eyes of 5 patients with congenital cataract who underwent lensectomy were used as controls.Methods: The ROP eyes were divided into 2 groups according to vascular activity: 12 eyes with vascularly active ROP and 15 eyes with vascularly inactive ROP. Undiluted vitreous samples were collected, and the vitreous concentrations of 27 types of cytokines were determined by a multiplex bead analysis system: interleukin (IL)-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, fibroblast growth factor (FGF) basic, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-r, interferon-γ-inducible protein (IP)-10, monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor bb, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor α, and vascular endothelial growth factor (VEGF).Main Outcome Measures: The vitreous levels of the 27 types of cytokines and a comparison of the levels in the 3 groups.Results: The postmenstrual age at vitrectomy was significantly younger in the vascularly active ROP eyes than in vascularly inactive ROP eyes. The cytokines that had significantly different vitreous levels among the 3 groups were: IL-6, IL-7, IL-10, IL-15, Eotaxin, FGF basic, G-CSF, GM-CSF, IP-10, RANTES, and VEGF (P<0.05). The vitreous levels of IL-6, IL-7, IL-15, Eotaxin, G-CSF, IP-10, and RANTES were significantly higher (P<0.05) in both vascularly active and inactive ROP eyes than in control eyes, whereas the vitreous level of VEGF was significantly higher (P<0.05) only in vascularly active ROP eyes than in control eyes. There was a significantly negative correlation (r = –0.382; P = 0.0495) between the VEGF level and the postmenstrual age at vitrectomy.Conclusions: These results indicate that, although cytokines other than VEGF may be involved in the pathologic changes in eyes with ROP, VEGF is likely to have the strongest correlation with the vascular activity in ROP eyes among these cytokines.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Blindness in a 25-Year Follow-up of a Population-Based Cohort of Danish Type 1 Diabetic Patients

Jakob Grauslund, Anders Green, Anne Katrin Sjølie — 2009-09-10

Purpose: To assess the long-term incidence of blindness and to evaluate risk factors for blindness in a population-based cohort of type 1 diabetic patients.Design: Retrospective cohort study.Participants: A population-based cohort of 573 type 1 diabetic patients, all of whom participated in a clinical ophthalmologic examination in 1981 and 1982 and were followed up for 25 years.Methods: At the baseline examination in 1981 and 1982, visual acuity, level of retinopathy, maculopathy, hemoglobin A1 (HbA1), proteinuria, smoking habits, and blood pressure were evaluated and related to the subsequent development of blindness. Blindness was defined as present in patients who were registered as members of the Danish Association of the Blind between baseline and January 2007. The Danish Association of the Blind is a voluntary organization open for all patients with a best-corrected visual acuity in the best eye of ≤6/60 (20/200) or with complications (i.e., visual fields <10°) subjectively leading to a best-corrected visual acuity in the best eye of ≤6/60 (20/200).Main Outcome Measures: Evaluation of 25-year incidence of blindness, predictors for blindness, and gender-specific incidence rates for blindness.Results: The 25-year cumulative crude incidence of blindness was 7.5% (men, 8.0%; women, 6.8%; P = 0.61), corresponding to a mortality-adjusted cumulative incidence of blindness of 9.5% (95% confidence interval [CI], 7.1%–12.0%) and an overall incidence rate of blindness of 4.11 per 1000 person-years (95% CI, 3.03–5.59 per 1000 person-years). Blindness was predicted by HbA1 and maculopathy at baseline. The odds ratio of blindness during follow-up was 1.69 (95% CI, 1.01–2.84) for a 1% increase in baseline HbA1 and was 6.18 (95% CI, 1.18–32.47) and 8.61 (95% CI, 2.54–29.23) for patients with maculopathy in combination with nonproliferative retinopathy and proliferative retinopathy, respectively. Age and duration at baseline, gender, proteinuria, smoking, systolic and diastolic blood pressure, and visual acuity at baseline were not associated with the development of blindness. Mortality was higher in patients who had become blind (61.0% vs. 42.1%; P = 0.02).Conclusions: Blindness is still a common complication in type 1 diabetes. Glycemic regulation and the presence of maculopathy are important risk factors for the development of blindness.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study

2009-08-24

Objectives: To compare ranibizumab with focal/grid laser or a combination of both in diabetic macular edema (DME).Design: Prospective, randomized, interventional, multicenter clinical trial.Participants: A total of 126 patients with DME.Methods: Subjects were randomized 1:1:1 to receive 0.5 mg of ranibizumab at baseline and months 1, 3, and 5 (group 1, 42 patients), focal/grid laser photocoagulation at baseline and month 3 if needed (group 2, 42 patients), or a combination of 0.5 mg of ranibizumab and focal/grid laser at baseline and month 3 (group 3, 42 patients).Main Outcome Measures: The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at month 6.Results: At month 6, the mean gain in BCVA was significantly greater in group 1 (+7.24 letters, P = 0.01, analysis of variance) compared with group 2 (−0.43 letters), and group 3 (+3.80 letters) was not statistically different from groups 1 or 2. For patients with data available at 6 months, improvement of 3 lines or more occurred in 8 of 37 (22%) in group 1 compared with 0 of 38 (0%) in group 2 (P = 0.002, Fisher exact test) and 3 of 40 (8%) in group 3. Excess foveal thickness was reduced by 50%, 33%, and 45% in groups 1, 2, and 3, respectively.Conclusions: During a span of 6 months, ranibizumab injections by the current protocol had a significantly better visual outcome than focal/grid laser treatment in patients with DME.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Five-year Results of a Randomized Trial with Open-label Extension of Triamcinolone Acetonide for Refractory Diabetic Macular Edema

2009-10-01

Objective: To report 5-year outcomes from a clinical trial of intravitreal triamcinolone acetonide (IVTA) in eyes with diabetic macular edema (DME) and impaired vision despite previous laser treatment.Design: Prospective, double-masked, randomized clinical trial. After completing the 2-year visit, all eyes, including those initially randomized to receive placebo, received IVTA according to prospectively defined guidelines.Participants and Controls: A total of 69 eyes (41 patients) were entered into the study, with 34 eyes initially receiving active treatment and 35 eyes receiving placebo. Five-year data were available for 44 of 67 eyes (66%). For the 23 eyes with missing 5-year data, of which 13 received placebo and 10 received IVTA, the last observation was carried forward.Intervention: Intravitreal injection of 0.1 ml of 40 mg/ml triamcinolone acetonide with adjunctive laser therapy where appropriate.Main Outcome Measures: Improvement of best-corrected logarithm of the minimum angle of resolution visual acuity by ≥5 letters after 5 years compared with baseline and 2 years, and incidence of adverse events. Secondary outcome was the change in central macular thickness.Results: Improvement of ≥5 letters after 5 years was found in 14 of 33 eyes (42%) initially treated with IVTA compared with 11 of 34 eyes (32%) initially treated with placebo (zGEE = 0.81, P = 0.4). Foveal thickness decreased by 30 μm (95% confidence interval, −47 to 107 μm) less in the initial-IVTA group than in the initial-placebo group at 5 years (zGEE = 0.76, P = 0.45); 5 of 11 eyes (45%) from the initial-IVTA group that were phakic at commencement of the third year required cataract surgery. A similar number of eyes from each group required ongoing treatment from the third year onward with both laser and IVTA, indicating that IVTA treatment for 2 years does not lead to reduction in the risk of recurrent edema.Conclusions: The majority of eyes that initially improved with IVTA maintained their gain after 5 years. No new safety concerns were identified. IVTA treatment may be considered in carefully selected cases of impaired vision caused by advanced DME that are unresponsive to other interventions.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Methotrexate for Ocular Inflammatory Diseases

2009-09-14

Purpose: To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation.Design: Retrospective cohort study.Participants: Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate 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, route of administration of methotrexate, 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, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy.Results: Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for ≥28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone ≤10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing (≤10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment.Conclusions: Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment.Financial Disclosure(s): The authors have no proprietary or commercial interests in any of the materials discussed in this article.

Congenital Toxoplasmosis in Southeastern Brazil: Results of Early Ophthalmologic Examination of a Large Cohort of Neonates

2009-09-10

Objective: To report results of early ophthalmologic examinations in a large cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening.Design: Cross-sectional analysis of a cohort.Participants: A total of 178 newborns with confirmed CT from 146,307 screened babies (95% of live births) from Minas Gerais state, southeastern Brazil.Methods: From November 2006 to May 2007, newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried blood samples. On all positive or suspected cases, confirmative serology was performed on babies and their mothers. Congenital toxoplasmosis was confirmed in newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic studies of the central nervous system were also performed. In selected cases, biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B-scan) was performed.Main Outcome Measures: Prevalence of retinochoroidal lesions, either cicatricial or active, and their location and associated findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal detachment, were evaluated. The occurrence of cataract, microphthalmia, microcephaly, intracranial calcification, and hydrocephalus was also recorded.Results: Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in 770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic examination at an average age of 55.6±16.6 days. Of these 178 infants, 142 (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye. Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in 142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes (12.4%).Conclusions: A high prevalence of CT was encountered (1/770) with high rates of early retinochoroidal involvement (∼80%) and many active lesions (in ∼50%), indicating a possibly more severe ocular involvement by CT in Brazil than in other parts of the world. The hypotheses of higher parasite virulence and increased individual susceptibility are being currently investigated.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Adjuvant Interferon Therapy for Patients with Uveal Melanoma at High Risk of Metastasis

2009-09-10

Purpose: To examine whether interferon (IFN)-alfa-2a treatment after radiation or enucleation reduces death rates in patients with uveal melanoma.Design: Interventional, comparative case series.Participants: Subjects were identified through the ocular oncology clinic of the Massachusetts Eye and Ear Infirmary. Patients eligible for the study were at increased risk of metastasis because of the presence of at least one of the following characteristics: age ≥65 years, largest tumor diameter (LTD) ≥15 mm, ciliary body involvement of the tumor, or extrascleral tumor extension.Methods: Between May 1995 and June 1999, 121 patients with choroidal or ciliary body melanoma began a 2-year course of therapy (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of primary therapy. All patients underwent regular monitoring for drug toxicity. To evaluate IFN-alfa-2a efficacy, we selected a series of historical controls frequency-matched (2:1) to IFN-alfa-2a–treated patients on age (±5 years), LTD (±3 mm), gender, and survival time between primary therapy and initiation of IFN therapy. Survival status was ascertained for all patients through December 2006.Main Outcome Measures: Melanoma-related mortality, metastasis, IFN-related toxicities.Results: Fifty-five patients (45%) completed therapy; the median dose for IFN-alfa-2a–treated patients was 792 MIU (85% of the theoretic dose). The median follow-up time in the IFN-alfa-2a–treated group was approximately 9 years. Treatment and control groups were similar with respect to age (P = 0.78), LTD (P = 0.38), and gender (P = 1.0). Of 363 patients, 108 developed metastasis under observation; 42 of these were IFN-alfa-2a–treated patients. Cumulative 5-year melanoma-related death rates were 17% in the radiation or enucleation-only group, 15% in those who completed the entire IFN-alfa-2a course, and 35% in those who discontinued IFN-alfa-2a therapy. In multivariate Cox regression, IFN-alfa-2a had no significant influence on melanoma-related mortality (rate ratio = 1.02, 95% confidence interval, 0.68–1.5, P = 0.91) or all-cause mortality (rate ratio = 0.84, 95% confidence interval, 0.58–1.2, P = 0.34).Conclusions: Interferon-alfa-2a has no material influence on survival in patients with choroidal melanoma.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Malignant Transformation of Congenital Hypertrophy of the Retinal Pigment Epithelium

Jerry A. Shields, Ralph C. Eagle, Carol L. Shields, Gary C. Brown, Sara E. Lally — 2009-09-10

Purpose: To report a clinicopathologic correlation of an adenocarcinoma that arose from solitary congenital hypertrophy of the retinal pigment epithelium (CHRPE).Design: Case report with clinicopathologic correlation.Methods: A 56-year-old black woman was referred for an asymptomatic fundus lesion in her left eye. It had features typical of CHRPE, but there was a small elevated nodule within the flat component, and the diagnosis was adenoma of the retinal pigment epithelium (RPE) arising from CHRPE. The lesion was observed periodically. The nodule slowly enlarged, and increasing amounts of lipoproteinaceous exudation accumulated in the adjacent retina. Thirteen years after the initial diagnosis, the patient returned with severe visual loss and no view of the fundus resulting from cataract and posterior synechia. Ultrasonography revealed a total retinal detachment and a pedunculated tumor measuring 7.5 mm in thickness. The eye was enucleated and studied histopathologically.Main Outcome Measures: Clinical evaluation and correlation of clinical findings with histopathologic results of the enucleated eye.Results: Histopathologically, the mass was composed of a proliferation of atypical RPE cells with a marked infiltration of benign plasma cells. Typical features of CHRPE were present at the base of the tumor. The final diagnosis was adenocarcinoma arising from CHRPE.Conclusions: Congenital hypertrophy of the retinal pigment epithelium, once considered to be a benign and stationary lesion, may spawn a malignant neoplasm.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Sentinel Lymph Node Biopsy for Ocular Adnexal Melanoma: Experience in 30 Patients

2009-09-22

Purpose: To report the findings on sentinel lymph node biopsy (SLNB) in 30 patients with ocular adnexal (conjunctival or eyelid) melanomas.Design: Prospective nonrandomized clinical trial.Participants: Thirty patients with diagnosis of eyelid or conjunctival melanoma.Methods: All patients with ocular adnexal melanoma who underwent SLNB at The University of Texas MD Anderson Cancer Center between December 2000 and July 2008 are the subject of this report. Sentinel lymph node biopsy was performed as previously described by our group, and patients were prospectively followed up.Main Outcome Measures: Findings on preoperative lymphoscintigraphy, SLNB, histopathologic examination of the primary tumor and sentinel lymph nodes (SNL), and nodal recurrence after SLNB.Results: Tumor sites were as follows: bulbar conjunctiva only, 14 patients; palpebral conjunctiva only, 8 patients; both bulbar and palpebral conjunctiva, 4 patients; and eyelid skin only, 4 patients. At least 1 SLN was identified in all patients. The median number of SLNs removed was 2 (range, 1–5). The most common basin sampled was the intraparotid (16 patients), followed by submandibular (level I) (11 patients), preauricular (9 patients), and superior cervical (level II) (6 patients). Five patients had SLN metastasis. Among the 25 patients with negative SLNB findings, there were 2 false-negative events. There were no false-negative events among patients treated during the last 4.5 years of the study. The mean Breslow thickness was 2.57 mm (range, 0.62–12 mm) among patients with negative SLNB and 4.86 mm (range, 2.0–7.2 mm) among patients with positive SLNB findings (P = 0.055). Ulceration was present in 11 patients (39%): 4 (80%) of 5 patients with positive SLNB and 7 (28%) of 25 with negative SLNB, including both patients with false-negative results. The median time from SLNB to last contact was 2 years (range, 10 months to 6 years).Conclusions: Sentinel lymph node biopsy is effective for identifying nodal micrometastasis in patients with ocular adnexal melanoma and provides important prognostic information. The false-negative event rate in our series improved in the last 4 years, most likely because of a better technique and better patient selection for SLNB. We recommend consideration of SLNB for patients with intermediate-thickness ocular adnexal melanoma and those with ulceration.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cilial Entropion: Surgical Outcome with a New Modification of the Hotz Procedure

Hirohiko Kakizaki, Dinesh Selva, Igal Leibovitch — 2009-09-10

Purpose: To report the surgical outcome with a new modification of the Hotz procedure for cilial entropion repair.Design: Retrospective case series.Participants: Forty-nine lower eyelids of 29 patients (22 female, 7 male; average age 8.4 years, range 2–27 years).Methods: The study included all patients diagnosed with cilial entropion and significant ocular irritation causing epiphora, photophobia, and ocular discharge, with or without keratitis. Surgery is based on dividing the anterior layer of the lower eyelid retractors from the anterior tarsal plate surface, definite identification of the inferior tarsal plate border, and reinforcement of the skin to the tarsal plate and lower eyelid retractors. Surgical outcome was defined as “good” or “fair” when there was no contact between the eyelashes and the globe or when less than 5 asymptomatic eyelashes had direct contact with the globe, respectively. A “poor” outcome was defined as either the majority of eyelashes remained in contact with the globe or persistence of irritation/keratitis in the presence of residual in-turned eyelashes. A successful outcome (“good” or “fair”) required no additional surgical intervention.Main Outcome Measures: Surgical outcome (“good,” “fair,” or “poor”), postoperative complications, recurrence.Results: During a mean follow-up period of 27.4 months (range, 3–50 months), 40 eyelids (82%) were judged postoperatively as “good,” 7 eyelids (14%) were judged as “fair,” and 2 eyelids (4%) were judged as “poor.” The 2 eyelids with a poor outcome were reoperated successfully using the same technique. No postoperative complications were recorded. There were no cases of recurrence, except the 2 eyelids with a “poor” outcome, during the follow-up period.Conclusions: Our modification of the Hotz procedure is based on identifying and dividing the anterior layer of the lower eyelid retractors and reinforcing the skin to the lower border of the inferior tarsal plate and lower eyelid retractors. This is a useful and predictive technique for cilial entropion repair and results in a high success rate.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Lacrimal Excretory System Concretions: Canalicular and Lacrimal Sac

Daniel J. Repp, Cat N. Burkat, Mark J. Lucarelli — 2009-09-10

Purpose: To characterize the demographics of patients with dacryolithiasis and to compare patients who have canalicular concretions with patients who have lacrimal sac and duct dacryoliths.Design: Comparative case series study and literature review.Participants: A total of 327 consecutive patients undergoing external dacryocystorhinostomy (DCR) between 1998 and 2008 at the University of Wisconsin-Madison. Fifteen consecutive patients with the diagnosis of canaliculitis during this period were also included.Methods: The charts of all patients were reviewed for age, sex, laterality, duration of symptoms, history of dacryocystitis, history of lacrimal system intervention, history of smoking, examination findings, result of canalicular probing and irrigation, and histopathologic evaluation of the dacryolith or canalicular concretion. If applicable, the canaliculus involved was noted, as was any history of purulent canalicular drainage or canalicular injury.Main Outcome Measures: Patient demographics, duration of symptoms, history of dacryocystitis, history of smoking, presence of fungi, or Actinomyces on histopathologic evaluation. Findings were compared with prior studies reported in the literature.Results: Of the 327 patients undergoing DCR, 22 (6.7%) had dacryoliths; 11 of 15 patients (73.3%) with canaliculitis had canalicular concretions. Patients with canalicular concretions were older than those with dacryoliths at DCR: 70.6 years versus 51.1 years (P = 0.003). Women made up the majority of both groups: 9 of 11 patients (81.8%) with canalicular concretions and 13 of 22 patients (59.1%) with dacryoliths at DCR (P = 0.26). The mean duration of symptoms was 20.2 months among patients with canalicular concretions and 30.5 months in patients with dacryoliths at DCR (P = 0.66); 1 of 11 patients (9.1%) with canalicular concretions smoked, compared with 9 of 21 patients (42.9%) with dacryoliths at DCR (P = 0.11). Actinomyces was isolated from 10 of 11 canalicular concretions (90.9%) and only 3 of 22 dacryoliths (13.6%) from DCR (P<0.001). In none of the 11 canalicular concretions were fungi identified, compared with 2 of 22 dacryoliths (9.1%) from DCR (P = 0.54).Conclusions: The demographics of patients with dacryoliths and the histopathology of their concretions vary with the location of the dacryolith in the lacrimal excretory system.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Ice Pack Test in the Differential Diagnosis of Myasthenic Diplopia

2009-09-10

Purpose: To investigate the diagnostic value and to establish threshold criteria for the ice pack test as an office preliminary test in the differential diagnosis of myasthenic diplopia in comparison with blepharoptosis.Design: Prospective, comparative cohort study.Participants: Eighty-nine patients with a recent onset of diplopia, blepharoptosis, or both were evaluated with orbital cooling in a prospective manner. Forty-eight patients presented with diplopia, 25 patients with both blepharoptosis and ophthalmoplegia and 16 patients with blepharoptosis.Testing: All patients had the ice pack applied for 5 minutes on both eyelids at the initial orthoptic evaluation. Increasing the duration of cooling to 10 minutes was investigated in 36 diplopic patients. A complete diagnostic work-up was ordered and patients were followed up for a minimum of 6 months before diagnosis of myasthenia gravis was ascertained.Main Outcome Measures: Difference in cover test measurements in primary position or marginal reflex distance before and after the application of the ice pack, specific cause for diplopia and blepharoptosis.Results: Fifteen patients were diagnosed as myasthenic. The optimal cutoff point for a positive response to the ice pack test proved to be a reduction in ocular deviation in primary position by 50% or by 10 prism diopters (PD) or more for presenting deviations larger than 20 PD. By this criterion, sensitivity for the detection of myasthenic diplopia was 76.9% (95% confidence interval [CI], 49.06%–92.50%) for the 5-minute application, compared with 92.3% (95% CI, 63.5%–98.9%) sensitivity demonstrated for blepharoptosis. Increasing the time of application to 10 minutes did not improve the diagnostic value of the test. Specificity was high (98.3%; 95% CI, 90.3%–99.9%) and was demonstrated even in patients with coexisting myasthenic and dysthyroid ophthalmopathy. Patients with oculomotor nerve paresis and Horner syndrome invariably were nonresponsive to the test.Conclusions: The ice pack test demonstrated high specificity and an acceptable sensitivity in the differential diagnosis of myasthenic diplopia. Data from this series suggest that a partial rather than a complete response to the ice pack test may be expected for myasthenic diplopia. Standardization of the method of application of the ice pack is critical for the interpretation of its effect.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Phakic Intraocular Lens Implantation for the Correction of Myopia: A Report by the American Academy of Ophthalmology

2009-11-01

Objective: To review the published literature for evaluation of the safety and outcomes of phakic intraocular lens (pIOL) implantation for the correction of myopia and myopic astigmatism.Methods: Literature searches of the PubMed and Cochrane Library databases were conducted on October 7, 2007, and July 14, 2008. The PubMed search was limited to the English language; the Cochrane Library was searched without language limitations. The searches retrieved 261 references. Of these, panel members chose 85 papers that they considered to be of high or medium clinical relevance to this assessment. The panel methodologist rated the articles according to the strength of evidence.Results: Two pIOLs have been approved by the US Food and Drug Administration (FDA): one iris-fixated pIOL and one posterior-chamber IOL. In FDA trials of iris-fixated pIOLs, uncorrected visual acuity (UCVA) was ≥20/40 in 84% and ≥20/20 in 31% after 3 years. In FDA trials of posterior-chamber pIOLs, UCVA was ≥20/40 in 81% and ≥20/20 in 41%. Satisfaction with the quality of vision with both types of pIOLs was generally high. Toric anterior- and posterior-chamber pIOLs have shown improved clinical results in European trials compared with spherical pIOLs. Comparative studies showed pIOLs to provide better best spectacle-corrected visual acuity (BSCVA) and refractive predictability and stability compared with LASIK and photorefractive keratectomy and to have a lower risk of retinal detachment compared with refractive lens exchange. Reported complications and long-term safety concerns include endothelial cell loss, cataract formation, secondary glaucoma (pupillary block, pigment dispersion), iris atrophy (pupil ovalization), and traumatic dislocation.Conclusions: Phakic IOL implantation is effective in the correction of myopia and myopic astigmatism. In cases of high myopia of −8 diopters or more, pIOLs may provide a better visual outcome than keratorefractive surgeries and better safety than refractive lens exchange. The short-term rates of complications and loss of BSCVA are acceptable. Comprehensive preoperative evaluation and long-term postoperative follow-up examinations are needed to monitor for and prevent serious complications, and to establish long-term safety.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Happy 50th Birthday

David Alvis — 2009-11-01

In mid-November, 1959 the first human fluorescein angiogram was performed on me, and photographs of my right eye were taken. An original 8×10 inch glossy print of that event with a copy of the paper Harold Novotny and I wrote for the journal Circulation is in the Museum of Vision of the American Academy of Ophthalmology.

Smoking and Corneal Biomechanics

Farhad Hafezi — 2009-11-01

Changes in the biomechanical properties of the human cornea play an important role in the pathogenesis of corneal dystrophies such as pellucid marginal corneal degeneration and keratoconus. The latter primarily affects young people and is a leading cause of severe visual impairment. Keratoconus is characterized by weakened corneal biomechanics that leads to progressive bulging and thinning of the cornea. Spoerl et al have shown recently that the incidence of keratoconus is distinctly reduced in smokers suggesting that smoking improves the biomechanical properties of the cornea. This hypothesis is further supported by studies showing that cigarette smoke contains compounds that enhance corneal biomechanics: formaldehyde crosslinks the cornea and experimentally increase the tissue's resistance to collagenases.

More on Schnyder Corneal Dystrophy

Jayne S. Weiss — 2009-11-01

I write concerning the recent report of Kobayashi et al. The authors solely credit Orr et al with identification of the UBIAD1 gene as the cause of Schnyder corneal dystrophy (SCD), but I would like to point out that our group independently discovered and published the finding that mutations in UBIAD1 gene caused SCD. Although the figure legends for the slit lamp photographs emphasize the central disciform opacity, crystalline deposits, and arcus lipoides; all of their patients also demonstrate the classic midperipheral corneal haze that is noted in patients 40 years of age and older but is often not appreciated. The authors reference an earlier publication of mine in which I introduced the name, Schnyder crystalline corneal dystrophy (SCCD) sine crystals to emphasize the acrystalline variety of SCD. The authors state that “in some cases a disciform opacity is present without evidence of crystals,” but I would like to emphasize that the acrystalline variety of the disease occurs very commonly, in up to 46% of affected individuals. Recently, we have published a revision of the corneal dystrophy nomenclature and SCCD has been renamed Schnyder corneal dystrophy (SCD) in order to deemphasize the finding of corneal crystals.

Author reply

Akira Kobayashi, Kazuhisa Sugiyama, Akira Murakami, Keiko Fujiki — 2009-11-01

We appreciate the interest and important comments from Dr. Weiss regarding our article on Schnyder corneal dystrophy.

Night Driving After LASIK

Sandra Brown — 2009-11-01

I read with interest the article by Schallhorn et al comparing night driving performance after conventional (c-) and wavefront-guided (w-) laser in situ keratomileusis (LASIK). Testing was performed with a night driving simulator (NDS), and I have personally undergone this fascinating process. I congratulate the authors for using a legitimate assessment of an important life function as opposed to an inadequate proxy such as self-reported difficulty on a satisfaction survey.

Author reply

Steve Schallhorn, Dave Tanzer, Sandor Kaupp, Mitch Brown — 2009-11-01

We would like to thank Dr. Brown for her interest in our paper and allowing us to more fully describe our low-light pupil testing protocol. We measured the low-light pupils with the infrared pupillometer incorporated into the Nidek auto-refractor (Nidek, Gamagori, Japan). All patients followed a specific testing protocol which began when they were brought into a dimly lit testing room and allowed to dark adapt for several minutes. The room light level was specifically matched to the luminance of the night driving simulator (1 cd/m2), which represented the reflection of headlights off of the pavement. The patients were then instructed to position their chin into the Nidek device where they viewed an object at optical-infinity. The examiner observed and sequentially measured the largest pupil diameter of each eye.

USG B Scan for Retinal Tears in PVD

Kapil Bhatia, Raja Narayanan — 2009-11-01

We read with interest the article by Lorenzo-Carrero et al entitled, “B-scan ultrasonography to screen for retinal tears in acute symptomatic age-related posterior vitreous detachment.” We offer a few comments.

Author reply

José Lorenzo-Carrero — 2009-11-01

I read attentively Bhatia and Narayanan's comments questioning the gold standard used in our study. They suggest that funduscopic examination (the gold standard for posterior vitreous detachment [PVD] evaluation) should have been performed by 1 or 2 retina specialists in a standardized manner instead of general ophthalmologists. In agreement with their comments, in the introduction and discussion sections, we have recognized that indirect ophthalmoscopy with indentation is the gold standard technique to examine the peripheral retina in PVD cases. Our approach to validate the index test was based on the following assumptions.

Angiographic Changes after Bevacizumab

Yasushi Ikuno, Kaori Soga, Taku Wakabayashi, Fumi Gomi — 2009-11-01

Intravitreal bevacizumab (IVB) (Avastin, Genentech Inc, South San Francisco, CA) is currently one of the most widely used treatments for myopic choroidal neovascularization (mCNV). IVB can improve and preserve vision in many patients at 1 year. However, the impact of IVB on the choroid/retinal pigment epithelium (RPE) is still uncertain. For example, marginal crack formation around the mCNV has been reported after treatment for mCNV. Indocyanine green angiography (ICGA) using a confocal system is useful for evaluating the RPE or choroidal damage in highly myopic eyes. We investigated the status of the RPE/choroid after IVB for mCNV.

Bevacizumab Local Complications

2009-11-01

Bevacizumab (Avastin, Genetech, San Francisco, CA) is a recombinant monoclonal antibody (IgG1) that selectively binds and neutralizes the biological activity of vascular endothelial growth factor. Its intravenous administration was approved by the Food and Drug Administration (FDA) in February 2004 as a first-line therapy for metastatic colorectal cancer.

Repair of Orbital Fractures

Daniel C. Garibaldi, Shannath L. Merbs, Michael P. Grant — 2009-11-01

We read with interest the article by Lane et al presenting the “sutureless” repair of orbital floor and rim fractures. We agree that this widely used technique has long been a successful alternative to multilayered conjunctival and periosteal closure in the repair of orbital fractures and were surprised to discover that it had not been previously described in detail. To the authors' 38 “pure” orbital floor fractures we would add 191 patients with isolated floor fractures who underwent successful repair using this approach and had been previously reported in papers discussing 2 distinct alloplastic implants.

Author reply

K.A. Lane, J.R. Bilyk, D. Taub, E.A. Pribitkin — 2009-11-01

We thank Dr. Garibaldi and colleagues for their comments regarding our recent publication and would like to comment on several issues raised in their correspondence. First, we do not claim to be the first to publish the “sutureless” technique for orbital fracture repair. In our paper, we clearly cite the work of Ho and colleagues, who described this technique in the repair of 26 isolated orbital floor fractures. Our series expanded the indications to include more complex orbital and midfacial fractures. As to the contention that this technique has been used by others, we have no way to confirm or refute this, except to state that such data did not appear in our review of the literature, nor was this noted during peer review. We also thank Dr. Garibaldi et al for adding their additional 191 cases, but we cannot comment on their results, since no detailed data is supplied in their letter. Furthermore, our reading of the 2 referenced series did not reveal any detail as to the presence or absence of periosteal and conjunctival closure. Of note, we limited our series to those cases with long-term follow-up. As Dr. Garibaldi et al are well-aware, such trauma-related data is often difficult to obtain for analysis secondary to relatively high rates of noncompliant follow-up.

Basal Cell Carcinoma

Paul S. Cannon, Shyamala C. Huilgol, Dinesh Selva, Raman Malhotra — 2009-11-01

We read with interest the recent article by Auw-Haedrich et al in which they set out to recommend an appropriate and reliable histological safety margin in the surgical excision of periorbital basal cell carcinoma (BCC). The authors conclude that in certain cases of incomplete excision where re-excision may lead to functional or cosmetic morbidity it may be reasonable to observe. This conclusion is based on their data of 11 patients with incompletely excised tumors of which 27% recurred.

Author reply

Claudia Auw-Haedrich, Stefanie Frick, Daniel Boehringer, Hans Mittelviefhaus — 2009-11-01

We are grateful to Cannon et al for their valuable comments on our study. For the patient's management it is important to differentiate between solid and fibrous basal cell carcinoma (BCC). We emphasize that we routinely re-excise cases with incompletely excised BCC, as we've recommended in our discussion. Even in solid BCC, when the histological margins are small (under 80 μm), we prefer to re-excise rather than leave a small histological safety margin. However, we believe our study's results could serve as a basis for discussing alternative approaches deserving of consideration when clinicians have to treat patients who refuse re-excision for whatever reason. Our experience has shown that most recurrences of solid BCCs don't just appear with deeply penetrated sections; they are usually also recognizable on the surface. Still, it is important that Dr. Cannon's warning of deep tumor recurrences has to be taken into account. Our study's tenor might also result from the fact that margin tumor cells of periorbital BCCs with incompletely excised margins tend to “vanish” more compared with other body regions (25% vs. 54% re-resection specimens containing tumor cells). Nevertheless, in conclusion, observation alone of patients with incompletely excised BCCs should be the exception in clinical practice, certainly not routine.

Systems-Based Competency

Andrew G. Lee — 2009-11-01

Dr. Lum and Dr. Schachat emphasized in their recent editorial the need to foster a culture of safety and transparency in order to reduce or preferably eliminate “never events” in ophthalmology (e.g., wrong site surgery or wrong intraocular lens). In a parallel process, the Accreditation Council for Graduate Medical Education (ACGME) has mandated that all residency programs in the U.S. teach and assess 6 general competencies. One of these competencies is systems-based practice (SBP), which the ACGME defines as follows: “Residents must demonstrate an awareness of and responsiveness to the larger context and system of health care and the ability to effectively call on system resources to provide care that is of optimal value.” Part of this awareness and responsiveness in the system of care is the identification of the root causes of medical error many of which arise from system errors (e.g., poor teamwork, inadequate team communication, process errors related to poor system checks and balances, or poor documentation). The actual “outcome” of the ACGME Outcome Project for the competencies should be improvement in downstream patient metrics (e.g., reduction of medical error, improved learner or patient satisfaction, increased quality and efficiency, or reduced cost). The alignment of the teaching and assessing of these competencies at the resident and fellow level with improvement in clinical outcomes in real patients will be the big payoff for the ACGME Outcome Project. The ACGME has mandated that programs use external data driven outcome measures to demonstrate individual and programmatic success. One of the keys to more widespread adoption and acceptance of the competencies will be for the stakeholders to use a common language for defining success. In my opinion, physician competency in systems-based practice is a critical first step in the quest to eliminate the “never events.”

Editorial Board

2009-11-01

This Issue At A Glance

Lori Baker Schena, John Kerrison — 2009-11-01

The Baltimore Pediatric Eye Disease Survey assessed the prevalence of strabismus and amblyopia among African-American and white preschool children aged 6 months through 71 months living in Baltimore city and adjacent Baltimore county. Among 4,132 children identified, 3,990 eligible children (97%) were enrolled and 2,546 (62%) were examined. Friedman et al (p. 2128) found that overall prevalence of strabismus was 2.1% in African Americans and 3.3% in whites, which was not a statistically significant difference. Exotropia and esotropia were found equally often in both racial groups, and were about 3 times more frequent in children after 12 months of age compared with the first year of life. In children 30 months to 71 months of age, the amblyopia prevalence was 1.8% for whites and 0.8% for African Americans, which was not statistically significant. National population projections show approximately 677,000 cases of manifest strabismus among U.S. children 6 months to 71 months and 271,000 cases of amblyopia among children 30 months to 71 months.

2009-11-01

Ophthalmology

Demographics, Etiology, and Behavior of Conjunctival Squamous Cell Carcinoma in the 21st Century

Complete Local Elimination of Infectious Trachoma from Severely Affected Communities after Six Biannual Mass Azithromycin Distributions

Ocular Manifestation in Treated Multibacillary Hansen's Disease

Proposed Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction

Average 3-Dimensional Models for the Comparison of Orbscan II and Pentacam Pachymetry Maps in Normal Corneas

Characteristics of Traumatic Globe Rupture after Keratoplasty

Endothelial Involvement in Herpes Simplex Virus Keratitis: An In Vivo Confocal Microscopy Study

Comparison and Evaluation of Ocular Biometry Using a New Noncontact Optical Low-Coherence Reflectometer

Visual Acuity Outcomes after Cataract Surgery in Patients with Age-Related Macular Degeneration: Age-Related Eye Disease Study Report No. 27

Variable Expressivity and High Penetrance of CYP1B1 Mutations Associated with Primary Congenital Glaucoma

Incidence and Rates of Visual Field Progression after Longitudinally Measured Optic Disc Change in Glaucoma

Refractive Errors in a Rural Chinese Adult Population: The Handan Eye Study

Prevalence of Amblyopia and Strabismus in White and African American Children Aged 6 through 71 Months: The Baltimore Pediatric Eye Disease Study

Nine-Year Incidence and Risk Factors for Age-Related Macular Degeneration in a Defined Japanese Population: The Hisayama Study

A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration

Photodynamic Therapy and Intravitreal Triamcinolone for Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial

Monitoring Ocular Drug Therapy by Analysis of Aqueous Samples

Simultaneous Analyses of Vitreous Levels of 27 Cytokines in Eyes with Retinopathy of Prematurity

Blindness in a 25-Year Follow-up of a Population-Based Cohort of Danish Type 1 Diabetic Patients

Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study

Five-year Results of a Randomized Trial with Open-label Extension of Triamcinolone Acetonide for Refractory Diabetic Macular Edema

Methotrexate for Ocular Inflammatory Diseases

Congenital Toxoplasmosis in Southeastern Brazil: Results of Early Ophthalmologic Examination of a Large Cohort of Neonates

Adjuvant Interferon Therapy for Patients with Uveal Melanoma at High Risk of Metastasis

Malignant Transformation of Congenital Hypertrophy of the Retinal Pigment Epithelium

Sentinel Lymph Node Biopsy for Ocular Adnexal Melanoma: Experience in 30 Patients

Cilial Entropion: Surgical Outcome with a New Modification of the Hotz Procedure

Lacrimal Excretory System Concretions: Canalicular and Lacrimal Sac

The Ice Pack Test in the Differential Diagnosis of Myasthenic Diplopia

Phakic Intraocular Lens Implantation for the Correction of Myopia: A Report by the American Academy of Ophthalmology

Happy 50th Birthday

Smoking and Corneal Biomechanics

More on Schnyder Corneal Dystrophy

Author reply

Night Driving After LASIK

Author reply

USG B Scan for Retinal Tears in PVD

Author reply

Angiographic Changes after Bevacizumab

Bevacizumab Local Complications

Repair of Orbital Fractures

Author reply

Basal Cell Carcinoma

Author reply

Systems-Based Competency

Editorial Board

This Issue At A Glance

Contents