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.
Author: Ophthalmology
Author reply – Corrected Proof
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…
Appearance of Regressing Drusen on Adaptive Optics in Age-Related Macular Degeneration – Corrected Proof
In age-related macular degeneration, material between the basal lamina of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane are generally referred to as drusen. Although drusen “maturation” is characterized by…
Retinal Blood Flow in Glaucomatous Eyes with Single-Hemifield Damage – Corrected Proof
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.
Comparison of Outcomes from a Phase 3 Study of Age-Related Macular Degeneration with a Matched, Observational Cohort – Corrected Proof
Objective: To compare outcomes of intravitreal therapy from an observational study cohort with those of participants receiving treatment in the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab (MARINA) for the treatment of neovascul…
Diagnostic Utility of Adipophilin Immunostain in Periocular Carcinomas – Corrected Proof
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.
Editorial Board
Fire Risk with Nasal Cannula Oxygen
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…
The Effect of Donor Age on Penetrating Keratoplasty for Endothelial Disease: Graft Survival after 10 Years in the Cornea Donor Study
Objective: To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age.Design: Multicenter, prospective, double-masked clinical trial.Participants: A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs’ dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years.Methods: Forty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons’ usual routines.Main Outcome Measures: Graft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months.Results: In the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, −1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P < 0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6.Conclusions: Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Cost-Utility of Cataract Surgery: The Real Issues
The cost-utility study of cataract surgery by Brown et al shows off the authors’ high degree of skill in conducting analyses of this type. Readers do not have to be concerned that the extremely favorable results on cataract surgery will be doubted bec…
Contents
期刊一览
Young (p. 2390) 等人对角结膜缘自体结膜移植术(LCAU)及术中使用丝裂霉素C对减少翼状胬肉复发的长期疗效进行了比较。他们也评估了丝裂霉素C对角膜内皮细胞密度(ECD)的影响。在随机、对照试验
A Simple Vista en Este Número
Young y otros (p. 2390), compararon el resultado a largo plazo del autoinjerto limbal conjuntival (LCAU) con el de la aplicación de mitomicina C (MMC) para minimizar la recurrencia del pterigio. Evaluaron también los efectos de la MMC en la densidad …
Evidence-Based Ophthalmology
It is easy to assume that colleagues are familiar with the structure and function of the international Cochrane Collaboration (List of contributors to CEVG available at http://aaojournal.org), but often this is off the mark or their understanding is misinformed. The Collaboration consists of >30 000 persons around the world who are committed to responding to Archie Cochrane’s challenge to the medical world in 1979:It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomized controlled trials.
Author reply
Sullivan-Mee et al questioned whether our longitudinal results demonstrating a relationship between lower corneal hysteresis (CH) and faster progression in glaucoma could perhaps be confounded by a relationship between CH and disease severity. They su…
Secukinumab in the Treatment of Noninfectious Uveitis
We read with interest the article by Dick et al on the efficacy and safety of different doses of secukinumab in patients with noninfectious uveitis in 3 multicenter, randomized, double-masked, placebo-controlled, dose-ranging, phase III studies in the…
How Will the Next Accreditation System Affect Ophthalmology Residency Training?
Years ago, imagine a co-resident who demonstrated suboptimal surgical skills early in residency. In some programs, this person would have received extra attention to bring his or her performance up to a passable level of competence. In others, the resi…
Scientific Reviewers
Cataract Surgery Cost Utility Revisited in 2012: A New Economic Paradigm
Objective: To assess the 2012 cost utility of cataract surgery in the United States and to compare 2012 cost-utility data with those from 2000.Design: Value-Based Medicine (Flourtown, PA), patient preference-based, comparative effectiveness analysis a…
This Issue At A Glance
Young et al (p. 2390) compared the long-term outcome of limbal conjunctival autograft (LCAU) with that of intraoperative applications of mitomycin C (MMC) in minimizing pterygium recurrence. They also evaluated the effects of MMC on corneal endothelia…