Category: Peer-reviewed

The Spectrum of Ocular Alterations in Patients with β-Thalassemia Syndromes Suggests a Pathology Similar to Pseudoxanthoma Elasticum – Corrected Proof

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Purpose: To determine the prevalence and spectrum of ocular fundus abnormalities in patients with β-thalassemia and to investigate risk factors for their development.Design: Cross-sectional, observational study.Participants: A total of 255 patients with β-thalassemia major (TM) and β-thalassemia intermedia (TI) were consecutively recruited and investigated.Methods: Patients underwent best correct visual acuity, indirect ophthalmoscopy, and fundus photography, including fundus autofluorescence (FAF) and near-infrared reflectance imaging using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters were determined, including mean ferritin levels, aspartate amino transferase, alanine amino transferase, calcium, pre-transfusion hemoglobin, history of splenectomy, and liver iron concentration. Factors associated with the ocular phenotype were assessed using logistic regression.Main Outcome Measures: Ocular phenotype as determined by clinical examination and used multimodal imaging.Results: A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%) affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau d’orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%), and optic disc drusen (2.0%). Pseudoxanthoma elasticum–like changes were more frequent in patients with TI (P < 0.001). Patients with PXE-like fundus changes were older than patients without these fundus changes (P < 0.001). In both patients with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest association with presence of PXE-like fundus changes in multivariate analyses. A total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity independently of the PXE-like fundus changes, which was associated with aspartate amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P = 0.005).Conclusions: Pseudoxanthoma elasticum–like fundus changes are a frequent finding in patients with β-thalassemia. In TI, these changes increase with duration or severity of the disease. This particular ocular phenotype suggests an ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional disease manifestation independent of the PXE-like syndrome. Patients with long-standing disease requiring iron-chelating treatment and a history of splenectomy need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials – Corrected Proof

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Objective: To describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).Design: Prospective cohort study within a randomized clinical trial.Participants: Patients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).Methods: Eyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation.Main Outcome Measures: Scar formation.Results: Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4–3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1–1.8), foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7–3.6) versus <120 μm, foveal subretinal tissue complex thickness >275 μm (aHR, 2.4; CI, 1.7–3.6) versus ≤75 μm, foveal subretinal fluid (aHR, 1.5; CI, 1.1–2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3–2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5–0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars.Conclusions: Approximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Associations between Health-Related Quality of Life and the Decision to Perform Surgery for Childhood Intermittent Exotropia – Corrected Proof

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Objective: To assess associations between health-related quality of life (HRQOL) and the decision to perform strabismus surgery for children with intermittent exotropia.Design: Retrospective chart review.Participants: Children with intermittent exotropia.Methods: Included subjects, identified in a clinical practice, had assessment of HRQOL using the intermittent exotropia questionnaire (IXTQ), comprising child, proxy, and parent components (parent domains: function, psychosocial, and surgery). The IXTQ scores were evaluated for association with surgery, along with standard clinical measures: prism and alternate cover test (PACT), stereoacuity, and control score (mean of the 3 most recent scores). Included data were from preoperative examination (surgical cohort) or from most recent follow-up examination (nonsurgical cohort). Univariate and multivariate logistic regression analyses were performed, and relative risk (RR) ratios were calculated. Spearman rank correlations were calculated to identify highly correlated items.Main Outcome Measures: Association of individual factors with the decision to perform surgery, calculated using RR ratios.Results: One hundred six children with intermittent exotropia (median age, 6 years; range, 2–16 years) were eligible for inclusion. Nineteen (18%) of 106 underwent surgery. Using all available data, the IXTQ proxy score, IXTQ parent function score, IXTQ parent psychosocial score, distance control score, near control score, near PACT, and Randot Preschool stereoacuity (Stereoptical Co, Inc, Chicago, IL) were associated with undergoing surgery (P<0.1). Sixty-nine of 106 patients had complete data on all factors identified in univariate analysis and were included in multivariate analyses. Fourteen (20%) of these 69 patients underwent surgery. In multivariate analyses, poor distance control score (RR, 1.83; 95% confidence interval [CI], 1.25–2.68) and reduced IXTQ parent function score (RR, 0.96; 95% CI, 0.92–0.99) were associated with surgical intervention. Repeat multivariate analyses retaining only 1 of the highly correlated items showed IXTQ proxy, IXTQ parent psychosocial, larger near PACT, and worse near control were also associated with surgery.Conclusions: After accounting for poorer exodeviation control at distance, reduced parent and proxy HRQOL were associated with undergoing strabismus surgery for childhood intermittent exotropia. Recognizing reduced parental HRQOL may be important, with a possible role for educational or counselling interventions.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Retinal Blood Flow in Glaucomatous Eyes with Single-Hemifield Damage – Corrected Proof

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Purpose: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere.Design: Prospective, nonrandomized, case-control study.Participants: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls.Methods: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed.Main Outcome Measures: Total and hemispheric RS, RBF, RNFL, and GCC values.Results: The total RBF (34.6±12.2 μl/minute) and venous cross-sectional area (0.039±0.009 mm2) were reduced (P < 0.001) in those with glaucoma compared with controls (46.5±10.6 μl/minute; 0.052±0.012 mm2). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3±5.4 vs. 19.3±8.4 μl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0±20.2 vs. 103.7±20.6 μm, P = 0.002; 77.6±12.1 vs. 83.6±10.1 μm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3±8.4 μl/minute), RNFL (103.7±20.6 μm), and GCC (83.6±10.1 μm) were reduced (P < 0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2±5.3 μl/minute, 124.8±9.6 μm, and 96.1±5.7 μm, respectively).Conclusions: In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Driving Habits in Older Patients with Central Vision Loss – Corrected Proof

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Objective: To determine if central visual loss is associated with driving cessation, driving restriction, or other-driver preference.Design: Cross-sectional study.Participants: Sixty-four subjects with bilateral visual loss (<20/32 in better eye) or severe unilateral visual loss (<20/200) from age-related macular degeneration (AMD) and 58 normally sighted controls between 60 and 80 years of age.Methods: Participants self-reported driving habits. Other-driver preference was defined as preferring that another drive when there is more than 1 driver in the car. Subjects reporting 2 or more driving limitations were considered to have restricted their driving.Main Outcome Measures: Self-reported driving cessation, other-driver preference, and driving restriction.Results: Age-related macular degeneration subjects were older (74.7 vs. 69.7 years), had worse visual acuity (VA; mean better-eye VA, 0.43 vs. 0.08 logarithm of minimum angle of resolution [logMAR]) and contrast sensitivity (CS; 1.4 vs. 1.9 log units of CS [logCS]), and were more likely to be white when compared with controls (P < 0.001 for all). Drivers with AMD-related vision loss were more likely to avoid driving over longer distances, beyond 1 hour, at night, and in unfamiliar conditions (P < 0.05 for all). In multivariate models, driving cessation was associated with worse better-eye VA (odds ratio [OR], 1.5 per 1-line decrement in VA; P < 0.001) and worse binocular CS (OR, 1.36 per 0.1 logCS increment; P = 0.005); however, AMD group status was not associated with driving cessation (OR, 1.9; P = 0.35). Factors predicting driving restriction were AMD (OR, 9.0; P = 0.004), worse vision (OR, 2.5 per line of VA loss; P < 0.001), lower CS (OR, 2.2 per 0.1-logCS increment; P < 0.001), and female gender (OR, 27.9; P = 0.002). Other-driver preference was more common with worse vision (OR, 1.6 per 0.1-logMAR increment; P = 0.003), female gender (OR, 4.5; P = 0.02), and being married (OR, 3.8; P = 0.04).Conclusions: Most patients with AMD-related central vision loss continue to drive, but demonstrate significant driving restrictions, especially with more severe VA and CS loss. Future work should determine which driving adaptations the visually impaired best balance safety and independence.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Diagnostic Utility of Adipophilin Immunostain in Periocular Carcinomas – Corrected Proof

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Purpose: To determine the efficacy of adipophilin immunohistochemistry in the diagnosis of sebaceous carcinoma of the ocular adnexal region and to provide the guidelines for interpretation of this immunostain.Design: Retrospective, histopathologic case series.Participants: A total of 25 patients with sebaceous carcinoma, 21 patients with basal cell carcinoma, 22 patients with conjunctival squamous cell carcinoma, 9 patients with cutaneous squamous cell carcinoma, and 5 patients with conjunctival mucoepidermoid carcinoma.Methods: Immunohistochemical staining for adipophilin was performed on paraffin-embedded tissues and correlated with hematoxylin–eosin, periodic acid–Schiff (PAS), and mucicarmine-stained preparations. Immunostaining was quantified by light microscopy and with a computerized image analysis system of scanned images. Statistical analysis was performed to compare immunostaining patterns within the tumor categories by stage and grade, between the different neoplasms, and for correlation between light microscopy observations and computerized image analysis.Main Outcome Measures: Localization of adipophilin immunostain, intensity of immunostaining, percent of immunoreactive cells, percentages of vacuolar staining and granular staining, and vacuole size.Results: Adipophilin expression was observed in 100% of sebaceous carcinomas, 100% of cutaneous squamous cell carcinomas, 95% of basal cell carcinomas, 73% of conjunctival squamous cell carcinomas, and 60% of mucoepidermoid carcinomas. Sebaceous carcinomas demonstrated significantly stronger adipophilin expression, a greater number of intracytoplasmic vacuoles, and larger vacuoles. The specificity and sensitivity of adipophilin immunostaining in the diagnosis of sebaceous carcinoma were both 100% when more than 5% of the staining occurred in vacuoles (<95% granular staining). The diagnostic sensitivity and specificity were 100% and 96%, respectively, when the staining was graded as moderately or strongly intense and were 92% and 85% when the vacuoles were greater than 1.5 μm in diameter.Conclusions: Although upregulation of neoplastic steatogenesis is observed in both sebaceous and nonsebaceous carcinomas, the pattern and intensity of adipophilin immunostaining are helpful in distinguishing sebaceous carcinoma from other neoplasms with overlapping histology.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Defining 10-2 Visual Field Progression Criteria: Exploratory and Confirmatory Factor Analysis Using Pointwise Linear Regression – Corrected Proof

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Purpose: To test different visual field progression criteria using trend analysis in a glaucoma population followed with long sequences of 10-2 tests as a first attempt to understand and document rates of progression in the central field.Design: Retrospective cohort study.Participants: We included 146 eyes of 146 patients with established glaucoma.Methods: Pointwise linear regression analysis using the methods of ordinary least squares was performed on the 68 test locations of the 10-2 visual field sequences. Threshold sensitivities at each test location were plotted as the dependent variable against follow-up time as the independent variable. Statistically significant progression or improvement of a visual field test point was defined if its regression slope measured ≤−1.0 dB/year or ≥+1.0 dB/year, respectively, at P < 0.01. We explored sets of criteria to define visual field progression, generating a hypothetical sensitivity (progression), specificity (improvement), and progression-to-improvement ratio (PIR) for each criterion. The criterion with the highest PIR was deemed the one with best performance. Latent class analysis (LCA) was used to determine visual field sectors with highest inter-correlation.Main Outcome Measures: The performance of different visual field progression criteria to detect fast rates of mean deviation (MD) change.Results: Median baseline 10-2 MD value was −12.0 dB (interquartile range [IQR], −6.7 to −17.8 dB), and the median rate of 10-2 MD change over time was −0.38 dB/year (IQR, −0.07 to −0.77 dB/year). The highest PIR was obtained with the progression criterion requiring at least 3 test points located in the same LCA-derived 10-2 visual field sector progressing faster than −1.0 dB/year at P < 0.01. This criterion was further validated for content and convergence.Conclusions: This is the first study to investigate progression criteria for 10-2 visual fields using rates of change and to test their performance and validity. These findings may be useful to improve the monitoring of patients with glaucoma at different levels of functional loss and to develop new perimetric algorithms that scrutinize specific visual field locations for a more accurate detection of progression.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Author reply – Corrected Proof

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We thank Tailor et al for their interest in our recent study describing cataract surgery in patients with nanophthalmos. They discuss the definition of nanophthalmos and microphthalmos. The most commonly used definition of nanophthalmos in recent stud…

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Genetic Susceptibility, Dietary Antioxidants, and Long-term Incidence of Age-related Macular Degeneration in Two Populations – Corrected Proof

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Objective: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk.Design: Pooled data analysis of population-based cohorts.Participants: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS).Methods: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], β-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses.Main Outcome Measures: All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale.Results: In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P = 0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P = 0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between β-carotene or vitamin C and genetic risk status.Conclusions: Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Fire Risk with Nasal Cannula Oxygen

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Huddleston et al raise awareness of fire hazards with supplemental oxygen during ophthalmic plastic surgery and succinctly outline the variables that contribute to devastating operating room fires. We question the conclusion that “insisting on nasal…

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