Objective Determination of Optimal Number of Spectral-Domain Optical Coherence Tomographic Images of Retina to Average

Purpose

To determine by objective methods the minimum number of spectral-domain optical coherence tomographic (SD-OCT) images to average to obtain the clearest retinal image.

Methods

SD-OCT Images were obtained from 9 healthy eyes and also from a phantom eye model. The SD-OCT images were obtained by averaging 1, 5, 20, 60, and 100 B-scan images. The reflectivity (mean gray value) of the different retinal layers was evaluated in these images. The image quality was evaluated by the size of the standard deviations (SDs) and the contrast-to-noise ratios (CNRs). A phantom eye model made by TiO₂ silicone plates was also examined.

Results

The SDs decreased significantly when the number of images averaged increased from 1 to 5 and also from 5 to 20 (P<0.05, post hoc Tukey''s honestly significant difference tests). The SD of the automatic real time averaging of 1 (ART = 1) and ART = 5 were significantly larger than the SD of ART = 100 (P<0.05). The SDs of all other averaged numbers were not significantly larger than that of ART = 100. The CNR increased with an increase in the number of images averaged, and there was a significant increase between ART = 1 to 5 and between ART = 5 to 20 (P<0.05). No significant differences in the CNR was observed between ART = 5, ART = 20 and ART = 60. Similar results were obtained with the phantom eye model.

Conclusions

Although the image quality of the SD-OCT images of the retina improved with an increase in the number of images averaged, it does not improve significantly by averaging more than 20 images.     

Retinal Nerve Fiber Layer Thickness. The Beijing Eye Study 2011

Purpose

To measure retinal nerve fiber layer (RNFL) thickness in a population-based setting.

Methods

In the population-based Beijing Eye Study 2011 with 3468 individuals, RNFL thickness was measured in a subgroup of 1654 (47.7%) study participants by spectral domain optical coherence tomography (iVue SD-OCT).

Results

Mean RNFL thickness was significantly (P<0.001) higher in the inferior sector (131.4±20.6 µm) than the superior sector (126.1±19.1 µm), where it was higher than in the temporal sector (79.8±12.2 µm;P<0.001), where it was higher than in the nasal sector (75.1±12.6 µm;P<0.001). In multivariate analysis, mean global RNFL thickness (103.2±12.6 µm) increased significantly with younger age (standardized correlation coefficient beta:−0.30;P<0.001), larger neuroretinal rim area (beta:0.26;P<0.001), shorter axial length (beta:−0.21;P<0.001), thicker subfoveal choroidal thickness (beta:0.15;P<0.001), larger optic disc area (beta:0.10;P<0.001), less refractive lens power (beta:0.10;P<0.001), flatter anterior cornea (beta:0.07;P = 0.01) and female gender (beta:0.05;P = 0.03). In this population with an age of 50+ years, the age-related decline in RNFL thickness was 0.5 µm per year of life or 0.36% of an original RNFL thickness of 137 µm at baseline of the study at 50 years of age. Mean global RNFL thickness decreased by 2.4 µm for each mm enlargement of axial length.

Conclusions

The RNFL profile shows a double hump configuration with the thickest part in the inferior sector, followed by the superior sector, temporal sector and nasal sector. Factors influencing global RNFL thickness were younger age, larger neuroretinal rim, shorter axial length, thicker subfoveal choroid, larger optic disc, less refractive lens power, flatter anterior cornea and female gender. Beyond an age of 50+ years, RNFL decreased by about 0.3% per year of life at an age of 50+ years and by 2.4 µm per mm of axial elongation. These findings may be of interest for the knowledge of the normal anatomy of the eye and may be of help to diagnose diseases affecting the RNFL.     

Changes in Refractive Errors Related to Spectacle Correction of Hyperopia

Background

Hyperopic undercorrection is a common clinical practice. However, less is known of its effect on the change in refractive errors and emmetropization throughout the later years of childhood.

Objectives

To evaluate the effect of spectacle correction on the change in refractive errors in hyperopic children less than 12 years of age with or without strabismus.

Data Extraction

A retrospective cohort study was performed by a computer based search of the hospital database of patients with hyperopia, accommodative esotropia or exotropia. A total of 150 hyperopic children under 12 years of age were included. Patients were classified into four groups: 1) accommodative esotropia with full correction of hyperopia, 2) exotropia with undercorrection of hyperopia, 3) orthotropia with full correction of hyperopia, 4) orthotropia with undercorrection of hyperopia. The 4 groups were matched by initial age on examination and spherical equivalent refractive errors (SER). The main outcome measure was the change in SER (Diopter/year) in both eyes after two years of follow-up.

Results

An overall negative shift in SER was noted during the follow-up period in all groups, except for the group with esotropia and full correction. The mean negative shift of hyperopia was more rapid in groups receiving undercorrection of hyperopia with or without strabismus. The amount of undercorrection of hyperopia was positively correlated to the magnitude of decrease in hyperopia in all patients (r = 0.289, P<0.001) and in the subgroup of patients with orthotropia (r = 0.304, P = 0.011). The amount of undercorrection of hyperopia was the only factor associated with a more negative shift in SER (OR, 2.414; 95% CI, 1.202–4.849; P = 0.013).

Conclusions

The amount of undercorrection is significantly correlated to the change in hyperopic refractive errors. Full correction of hyperopia may inhibit emmetropization during early and late childhood.     

Subfoveal Choroidal Thickness and Glaucoma. The Beijing Eye Study 2011

Purpose

To examine subfoveal choroidal thickness (SFCT) in eyes with glaucoma, using enhanced depth imaging spectral domain optical coherence tomography.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of SFCT, and assessment of fundus photographs for presence of glaucoma. In addition, the group of patients with chronic angle-closure glaucoma (ACG) from the Beijing Eye Study (n = 37) was merged with a group of patients with chronic ACG from the Tongren hospital (n = 52).

Results

Assessments of SFCT and glaucoma were available for 3232 (93.2%) subjects. After adjusting for age, axial length, gender, anterior chamber and lens thickness, SFCT was not significantly associated with presence of glaucoma (P = 0.08; regression coefficient B:−15.7). As a corollary, in logistic regression analysis with adjustment for age, axial length and intraocular pressure, presence of glaucoma was not significantly associated with SFCT (P = 0.20). If only open-angle glaucoma was considered, multivariate analysis revealed no significant association between SFCT and presence of open-angle glaucoma (P = 0.44). As a corollary, in logistic regression analysis, open-angle glaucoma was not significantly associated with SFCT (P = 0.91). In a similar manner if only ACG was taken into account, SFCT was not significantly associated with the presence of ACG (P = 0.27) in multivariate analysis. As a corollary in binary regression analysis, presence of ACG was not significantly associated with SFCT (P = 0.27).

Conclusions

In multivariate analysis with adjustment for age, axial length, gender, anterior chamber and lens thickness, neither OAG nor ACG was associated with an abnormal SFCT.     

Parapapillary Atrophy: Histological Gamma Zone and Delta Zone

Background

To examine histomorphometrically the parapapillary region in human eyes.

Methodology/Principal Findings

The histomorphometric study included 65 human globes (axial length:21–37 mm). On anterior-posterior histological sections, we measured the distance Bruch''s membrane end (BME)-optic nerve margin (“Gamma zone”), BME-retinal pigment epithelium (RPE) (“Beta zone”), BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. “Delta zone” was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm) was significantly (P = 0.01) larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28) associated with axial length. Beta zone was significantly (P = 0.004) larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm) was associated with axial length (P<0.001;r² = 0.73) with an increase starting at an axial length of 26.5 mm. It was not significantly (P = 0.24) associated with glaucomatous optic neuropathy. Delta zone (present only in eyes with axial length of ≥27 mm) was associated with axial length (P = 0.001) and scleral flange length (P<0.001) but not with glaucoma (P = 0.73).

Conclusions/Significance

Parapapillary gamma zone (peripapillary sclera without overlying choroid, Bruch''s membrane and deep retinal layers) was related with axial globe elongation and was independent of glaucoma. Delta zone (no blood vessels >50 µm diameter within gamma zone) was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch''s membrane without RPE) was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.     

Peripapillary Arterial Circle of Zinn-Haller: Location and Spatial Relationships with Myopia

Purpose

To measure histomorphometrically the location of the peripapillary arterial circle of Zinn-Haller (ZHAC) and assess its associations with axial length.

Methods

Using a light microscope, we measured the distance from the ZHAC to the peripapillary ring (optic disc border), the merging point of the dura mater with the posterior sclera (“dura-sclera point”), and the inner scleral surface. In the parapapillary region, we differentiated between beta zone (presence of Bruch''s membrane, absence of retinal pigment epithelium) and gamma zone (absence of Bruch''s membrane). The peripapillary scleral flange as roof of the orbital cerebrospinal fluid space was the connection between the end of the lamina cribrosa and the posterior full-thickness sclera starting at the dura-sclera point.

Results

The study included 101 human globes (101 patients) with a mean axial length of 26.7±3.7 mm (range: 20.0–39.0 mm). The distance between the ZHAC and the peripapillary ring increased significantly with longer axial length (P<0.001; correlation coefficient r = 0.49), longer parapapillary gamma zone (P<0.001;r = 0.85), longer (P<0.001;r = 0.73) and thinner (P<0.001;r = −0.45) peripapillary scleral flange, and thinner sclera posterior to the equator (P<0.001). ZHAC distance to the peripapillary ring was not significantly associated with length of parapapillary beta zone (P = 0.33). Including only non-highly myopic eyes (axial length <26.5 mm), the ZHAC distance to the disc border was not related with axial length (P = 0.84). In non-highly myopic eyes, the ZHAC was located close to the dura-sclera point. With increasing axial length and decreasing thickness of the peripapillary scleral flange, the ZHAC was located closer to the inner scleral surface.

Conclusions

The distance between the ZHAC and the optic disc border is markedly enlarged in highly myopic eyes. Since the ZHAC is the main arterial source for the lamina cribrosa blood supply, the finding may be of interest for the pathogenesis of the increased glaucoma susceptibility in highly myopic eyes.     

Effects of retinal dopamine depletion on the growth of the fish eye

We investigated the suitability of fishes as animal models to study the involvement of the retinal dopaminergic system in the visually guided control of eye growth (emmetropization). Advantages of such a model system are (i) that all dopaminergic cells in the retina can be destroyed without apparent damage to other neurons, (ii) simple optical design and short depth of field of the eye, and (iii) continuous growth throughout life. Depleting the retina of dopamine in Aequidens pulcher (Cichlidae) had no apparent effect on refractive state, since size and focal length of the eye were reduced by the same amount. Furthermore, imposed defocus was compensated at a normal rate in spite of the absence of retinal dopamine. In A. pulcher, the dopaminergic system of the retina thus appears not to have an essential role in emmetropization. Our results furthermore suggest that in eyes of more complicated optical design, manipulation of the retinal dopaminergic system may lead to unrelated effects indistinguishable from direct interference with emmetropization. A major disadvantage of the fish model was that refractive state of the eye could not be measured accurately in vivo with standard methods. Accepted: 9 January 1999     

Determination of Axial Length Requiring Adjustment of Measured Circumpapillary Retinal Nerve Fiber Layer Thickness for Ocular Magnification

Purpose

To determine the axial length requiring adjustment of measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness to account for ocular magnification during spectral-domain optical coherence tomography (SD-OCT).

Methods

In this prospective study, 148 eyes of 148 healthy student volunteers were imaged by two examiners using three-dimensional SD-OCT. In 54 randomly selected eyes, total cpRNFL thickness was measured with and without adjustment for ocular magnification to establish intra-examiner and inter-examiner measurement error. The 148 eyes were then divided into three groups according to the error values: control group (difference in the corrected and uncorrected total cpRNFL thickness was within the measurement error range), thinner group (the corrected total cpRNFL thickness was less than the uncorrected one), and thicker group (the corrected total cpRNFL thickness was more than the uncorrected one). The cutoff values of axial length between the control and the other groups were calculated by receiver operating characteristic analysis.

Results

Measurement error ranged from 4.2 to 5.3 µm; the threshold value was defined as 5.3 µm. The cutoff values of axial length between the thinner and the control groups and between the control and the thicker groups were 23.60 (area under the curve [AUC] = 0.959) and 25.55 (AUC = 0.944) mm, respectively.

Conclusions

Axial lengths shorter than 23.60 mm and longer than 25.55 mm require adjustment of measured cpRNFL thickness to account for ocular magnification during SD-OCT.

Clinical Trial Registration

UMIN Clinical Trials Registry (http://www.umin.ac.jp/) under unique trial number UMIN000013248 (date of registration: 02/24/2014)     

Assessment of the Association of Matrix Metalloproteinases with Myopia,Refractive Error and Ocular Biometric Measures in an Australian Cohort

Extracellular matrix proteins have been implicated in protein remodelling of the sclera in refractive error. The matrix metalloproteinases (MMPs) falling into the collagenase (MMP1, MMP8, MMP13), gelatinase (MMP2, MMP9) and stromelysin (MMP3, MMP10, MMP11) functional groups are particularly important. We wished to assess their association with myopia, refractive error and ocular biometric measures in an Australian cohort. A total of 543 unrelated individuals of Caucasian ethnicity were genotyped including 269 myopes (≤−1.0D) and 274 controls (>−1.0D). Tag single nucleotide polymorphisms (SNPs) (n = 53) were chosen to encompass these eight MMPs. Association tests were performed using linear and logistic regression analysis with age and gender as covariates. Spherical equivalent, myopia, axial length, anterior chamber depth and corneal curvature were the phenotypes of interest. Initial findings indicated that the best p values for each trait were 0.02 for myopia at rs2274755 (MMP9), 0.02 for SE at both rs3740938 (MMP8) and rs131451 (MMP11), 0.01 for axial length at rs11225395 (MMP8), 0.01 for anterior chamber depth at rs498186 (MMP1) and 0.02 at rs10488 (MMP1). However, following correction for multiple testing, none of these SNPs remained statistically significant. Our data suggests that the MMPs in the collagenase, gelatinase and stromelysin categories do not appear to be associated with myopia, refractive error or ocular biometric measures in this cohort.     

Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10⁻⁶², SLC24A5 P = 9.6×10⁻⁹) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10⁻²⁷, TYR P = 1.1×10⁻⁹, APBA2[OCA2] P = 1.5×10⁻⁸, SLC45A2 P = 6×10⁻⁹) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (∼44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ∼70% of the estimated heritability.     

Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma

Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10⁻¹¹). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10⁻¹⁰) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss.     

Macular Cone Abnormalities in Retinitis Pigmentosa with Preserved Central Vision Using Adaptive Optics Scanning Laser Ophthalmoscopy

Purpose

To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO).

Methods

Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images.

Results

In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT.

Conclusions

Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP.     

Comparison of Longitudinal In Vivo Measurements of Retinal Nerve Fiber Layer Thickness and Retinal Ganglion Cell Density after Optic Nerve Transection in Rat

Purpose

To determine the relationship between longitudinal in vivo measurements of retinal nerve fiber layer thickness (RNFLT) and retinal ganglion cell (RGC) density after unilateral optic nerve transection (ONT).

Methods

Nineteen adult Brown-Norway rats were studied; N = 10 ONT plus RGC label, N = 3 ONT plus vehicle only (sans label), N = 6 sham ONT plus RGC label. RNFLT was measured by spectral domain optical coherence tomography (SD-OCT) at baseline then weekly for 1 month. RGCs were labeled by retrograde transport of fluorescently conjugated cholera toxin B (CTB) from the superior colliculus 48 hours prior to ONT or sham surgery. RGC density measurements were obtained by confocal scanning laser ophthalmoscopy (CSLO) at baseline and weekly for 1 month. RGC density and reactivity of microglia (anti-Iba1) and astrocytes (anti-GFAP) were determined from post mortem fluorescence microscopy of whole-mount retinae.

Results

RNFLT decreased after ONT by 17% (p<0.05), 30% (p<0.0001) and 36% (p<0.0001) at weeks 2, 3 and 4. RGC density decreased after ONT by 18%, 69%, 85% and 92% at weeks 1, 2, 3 and 4 (p<0.0001 each). RGC density measured in vivo at week 4 and post mortem by microscopy were strongly correlated (R = 0.91, p<0.0001). In vivo measures of RNFLT and RGC density were strongly correlated (R = 0.81, p<0.0001). In ONT- CTB labeled fellow eyes, RNFLT increased by 18%, 52% and 36% at weeks 2, 3 and 4 (p<0.0001), but did not change in fellow ONT-eyes sans CTB. Microgliosis was evident in the RNFL of the ONT-CTB fellow eyes, exceeding that observed in other fellow eyes.

Conclusions

In vivo measurements of RNFLT and RGC density are strongly correlated and can be used to monitor longitudinal changes after optic nerve injury. The strong fellow eye effect observed in eyes contralateral to ONT, only in the presence of CTB label, consisted of a dramatic increase in RNFLT associated with retinal microgliosis.     

Multimodal Retinal Vessel Analysis in CADASIL Patients

Purpose

To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging.

Methods

28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD-OCT.

Results

Mean age of patients was 56.2±11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77±0.46 mm³ and 8.83±2.24 mm³. RNFL measurements showed a global increase of 105.2 µm (Control group: 98.4 µm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 µm (106.0 µm; p = 0.21) and 128.6 µm (124.4 µm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 µm (125.4 µm; p<0.001) and venous 160.0 µm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 µm (19.2 µm; p<0.001) and venous 18.3 µm (15.7 µm; p<0.001) wall thicknesses in CADASIL patients.

Conclusions

The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases.     

Age-Related Association of Refractive Error with Intraocular Pressure in the Korea National Health and Nutrition Examination Survey

Background

To investigate the distribution of intraocular pressure (IOP) and refractive errors according to age group in a representative sample of non-glaucomatous Korean adults.

Methods

A total of 7,277 adults (≥19 years) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011 underwent ophthalmic examination were divided into three groups according to age: the young- (19–39 years), middle- (40–59 years), and old- (≥60 years) age groups. Simple and multiple regression analyses between IOP and various parameters (including the refractive error) were conducted.

Results

The mean IOP of the total population was 14.0±0.1 mmHg [young: 13.9±0.1 mmHg; middle: 14.1±0.1 mmHg; old: 13.8±0.2 mmHg (P for trend = 0.085)]. Myopia and high myopia were more prevalent in the young- (70.8% and 16.1%, respectively), compared to the middle- (44.6% and 10.9%) and old- (8.9% and 2.2%) age groups. Univariate analysis in the total population showed that higher IOP was associated with myopic refractive error, the female gender, higher body mass index (BMI), diabetes, hypertension, and hypercholesterolemia (all P<0.05). In the young- and middle-age groups, higher IOP was associated with myopic refractive error, the female gender, higher BMI, hypercholesterolemia and diabetes (all P<0.05). In the old-age group, the association between IOP and refractive error was not significant (P = 0.828). In multiple linear regression analysis, similar significant relationships between the refractive error and IOP were found in the young- and middle-age groups (beta = −0.08 and −0.12; P = 0.002 and <0.001 for young- and middle-age group, respectively), but not in the old-age group (beta = 0.03; P = 0.728), after adjusting for age, gender, BMI, region of habitation, diabetes, hypertension, and hypercholesterolemia.

Conclusions

Myopic refractive error was an independent predictor of higher IOP in non- glaucomatous eyes, and the association between refractive error and IOP differed according to age.     

Admixture Mapping Scans Identify a Locus Affecting Retinal Vascular Caliber in Hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) Study

Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (ρ = 0.071, P = 0.003), but not CRAE (ρ = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = −0.73) or CRVE (genome-wide score = −0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 µm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.     

Prevalence and Associations of Incomplete Posterior Vitreous Detachment in Adult Chinese: The Beijing Eye Study

Purpose

To determine prevalence and associations of incomplete posterior vitreous detachment (PVD).

Methods

The population-based cross-sectional Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT). Incomplete PVD was differentiated into type 1 (shallow PVD with circular perifoveal vitreous attachment), type 2 (PVD reaching fovea but not foveola), type 3 (shallow PVD with pinpoint vitreous attachment at the foveola), and type 4 (PVD completely detached from the macula, attached to the optic disc).

Results

An incomplete PVD was detected in 3948 eyes (prevalence: 60.5±0.6%; 95% Confidence Interval (CI): 59.3%,61.7%) of 2198 subjects (67.1±0.8%;95%CI: 65.6%,68.7%). Type 1 PVD was seen in 3090 (78.3%) eyes, type 2 PVD in 504 (12.8%) eyes, type 3 PVD in 70 (1.8%) eyes, and type 4 PVD in 284 (7.2%) eyes. Prevalence of incomplete PVD was associated with younger age (P<0.001;OR:0.91), male gender (P<0.001;OR:0.64), rural region of habitation (P<0.001;OR:0.49), larger corneal diameter (P = 0.04;OR:0.91), better best corrected visual acuity (P = 0.02;OR:0.41), and hyperopic refractive error (P<0.001;OR:1.15). The type of incomplete PVD was associated with higher age (P<0.001), urban region of habitation (P<0.001), myopic refractive error (P = 0.001), thinner cornea (P = 0.005), and better best corrected visual acuity (P = 0.056).

Conclusions

In adult Chinese in Greater Beijing, prevalence of an incomplete PVD (detected in 67.1% subjects) was associated with younger age, male gender, rural region of habitation, larger corneal diameter, better best corrected visual acuity and hyperopic refractive error.     

Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10⁻⁸), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10⁻¹¹) and 8q12 (minimum p value 1.82×10⁻¹¹) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. “Replication-level” association was also seen between hyperopia and 12 of Kiefer et al.''s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.     

Prevalence and associations of steep cornea/keratoconus in Greater Beijing. The Beijing Eye Study

Purpose

To evaluate the prevalence and associated factors of steep cornea/keratoconus in the adult Chinese population.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including optical low-coherence reflectometry. Steep cornea/keratoconus were defined as an anterior corneal refractive power exceeding 48 diopters.

Results

Mean refractive power of the cornea was 43.16±1.45 diopters (range: 36.51 to 48.46 diopters; flattest meridian) and 43.98±1.52 diopters (range: 37.00 to 52.88 diopters; steepest meridian). A steep cornea/keratoconus defined as corneal refractive power of ≥48 diopters and ≥49 diopters was detected in 27 subjects (prevalence rate: 0.9±0.2%) and 6 (0.2± 0.1%) subjects, respectively. Presence of steep cornea/keratoconus was associated with shorter axial length (P<0.001), smaller interpupillary distance (P = 0.038), lower best corrected visual acuity (P = 0.021), higher cylindrical refractive error (P<0.001) and more myopic refractive error (P<0.001). It was not significantly associated with gender, body height, psychic depression, cognitive function, blood concentrations of glucose, lipids, creatinine and C-reactive protein, blood pressure and quality of life score, nor with intraocular pressure, dry eye feeling, and lens thickness.

Conclusions

A steep cornea/keratoconus defined as corneal refractive power of 48+ diopters has a prevalence of 0.9±0.2% among Chinese aged 50 years and above. Its prevalence was significantly associated with the ocular parameters of shorter axial length, smaller interpupillary distance, higher cylindrical and myopic refractive error and lower best corrected visual acuity, however, with none of the systemic parameters tested.