Category: Peer-reviewed

Investigation of Genetic Variation in Scavenger Receptor Class B, Member 1 (SCARB1) and Association with Serum Carotenoids – Corrected Proof

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Objective:
To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD).

Design:
A cross-sectional study of healthy adults aged 20 to 70.

Participants:
We recruited 302 participants after local advertisement.

Methods:
We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts.

Main Outcome Measures:
Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender.

Results:
After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10−4), an SNP in high linkage disequilibrium with rs11057841 (r2 = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses.

Conclusions:
Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina.

Financial Disclosure(s):
Proprietary or commercial disclosures may be found after the references.

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Age-related Macular Degeneration and Modification of Systemic Complement Factor H Production Through Liver Transplantation – Corrected Proof

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Purpose: To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD).Design: Multicenter, cross-sectional study.Participants: We recruited 223 Western European patients ≥55 years old who had undergone LT ≥5 years previously.Methods: We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor).Main Outcome Measures: We evaluated AMD status and recipient and donor CFH Y402H genotype.Results: In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0–2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014).Conclusions: Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

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Age-related Macular Degeneration and Modification of Systemic Complement Factor H Production Through Liver Transplantation – Corrected Proof

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Purpose: To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD).Design: Multicenter, cross-sectional study.Participants: We recruited 223 Western European patients ≥55 years old who had undergone LT ≥5 years previously.Methods: We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor).Main Outcome Measures: We evaluated AMD status and recipient and donor CFH Y402H genotype.Results: In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0–2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014).Conclusions: Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

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Effects of Different Sleeping Postures on Intraocular Pressure and Ocular Perfusion Pressure in Healthy Young Subjects – Corrected Proof

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Objective:
To investigate the effects of different sleeping positions of head and body on intraocular pressure (IOP) and ocular perfusion pressure (OPP) in healthy, young subjects.

Design:
Prospective, comparative case series.

Participants:
Twenty healthy young Korean subjects.

Methods:
We measured IOP and blood pressure (BP) with the subjects seated and recumbent, including supine, right lateral decubitus, left lateral decubitus, prone with right head turn, and prone with left head turn positions. We measured IOP using an Icare tonometer in both eyes 5 minutes after assuming each position in a randomized sequence. We calculated the OPP using the formulas based on the mean BP adjusted for the height of the eye over the heart. The eye on the lower side in the lateral decubitus or prone with head turn position was termed the dependent eye.

Main Outcome Measures:
Difference in IOP and OPP of the dependent and nondependent eyes during changes of sleeping positions of body and head.

Results:
Mean IOP of right and left eyes while sitting was significantly lower than that measured in each recumbent position (all P<0.001). The OPPs in both eyes were significantly higher in all recumbent positions than in a sitting position (all P<0.001). Mean IOP of the dependent eyes was higher than that of the nondependent eyes in the lateral decubitus positions and in the prone positions with head turns (all P<0.001). No significant intereye difference in OPP was found for any position. Among IOPs measured in the recumbent positions, mean IOP of the dependent eye in the lateral decubitus position or in the prone position with head turn was significantly higher than that of the ipsilateral eye in the supine position (all P<0.0001).

Conclusions:
All sleeping positions of head and body resulted in an elevation of IOP and an increase in the calculated OPP compared with the sitting position in healthy, young subjects. The postural change from supine to lateral decubitus or prone with head turn position increased the IOP of the dependent eyes without significant alteration in OPP in healthy awake subjects. Further research is needed under nocturnal conditions in a sleep laboratory.

Financial Disclosures:
The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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Reticular Pseudodrusen

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In 1990, our group first described reticular pseudodrusen as a peculiar yellowish pattern in the macula of age-related macular degeneration (AMD) patients, whose visibility was enhanced using blue light. More recently, using spectral-domain optical coh…

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We thank Zhang et al for their comments on our manuscript. Our group feels that it is important to look at the mean difference in axial length (AL) and also consider other key diabetic retinopathy (DR) risk factors, such as HbA1c and duration of diabet…

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We thank Casas-Llera et al for their interest in our study, the main purpose of which was to determine the level of agreement between the consensus judgment of expert clinicians and Glaucoma Progression Analysis (GPA) software with respect to the deter…

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A Simple Vista en Este Número

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Un estudio por Campochiaro y otros (p. 795) para evaluar la relación de bloquear el factor de crecimiento endotelial vascular (VEGF) en la progresión de la no perfusión de la retina (RNP) en pacientes con edema macular por oclusión de la vena centr…

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Neuro-ophthalmology Safer Than MRI?

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We read with interest the study “Neuroimaging in Patients Referred to a Neuro-Ophthalmology Service” by McClelland et al. They concluded that a high rate of suboptimal neuroimaging occurs before neuroophthalmology referral. They also pointed out th…

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We appreciate the interest that Bottoni et al have expressed with regard to our article “Vitrectomy without laser treatment or gas tamponade for macular detachment associated with an optic disc pit.” Their findings using optical coherence tomograph…

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We thank Sadun et al for their letter. We are in agreement that inappropriate testing leads not only to delays in final diagnosis and definitive treatment, but can result in further unnecessary testing and intervention. We would also amplify the point …

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