Lamina Cribrosa Insertions Into the Sclera Are Sparser, Narrower, and More Slanted in the Anterior Lamina.

Purpose: The lamina cribrosa (LC) depends on the sclera for support. The support must be provided through the LC insertions. Although a continuous insertion over the whole LC periphery is often assumed, LC insertions are actually discrete locations where LC collagenous beams meet the sclera. We hypothesized that LC insertions vary in number, size, and shape by quadrant and depth. Methods: Coronal cryosections through the full LCs from six healthy monkey eyes were imaged using instant polarized light microscopy. The images were registered into a stack, on which we manually marked LC insertion outlines, nothing their position in-depth and quadrant (inferior, superior, nasal, or temporal). From the marks, we determined the insertion number, width, angle to the canal wall (90 degrees = perpendicular), and insertion ratio (fraction of LC periphery represented by insertions). Using linear mixed effect models, we determined if the insertion characteristics were associated with depth or quadrant. Results: Insertions in the anterior LC were sparser, narrower, and more slanted than those in deeper LC (P values < 0.001). There were more insertions spanning a larger ratio of the canal wall in the middle LC than in the anterior and posterior (P values < 0.001). In the nasal quadrant, the insertion angles were significantly smaller (P < 0.001). Conclusions: LC insertions vary substantially and significantly over the canal. The sparser, narrower, and more slanted insertions of the anterior-most LC may not provide the robust support afforded by insertions of the middle and posterior LC. These variations may contribute to the progressive deepening of the LC and regional susceptibility to glaucoma.

OCT Optic Nerve Head Morphology in Myopia IV: Neural Canal Scleral Flange Remodeling in Highly Myopic Eyes.

PURPOSE: To compare the prevalence, location and magnitude of optic nerve head (ONH) OCT-detected, exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT) and exposed scleral flange (ESF) regions in 122 highly myopic (Hi-Myo) versus 362 nonhighly myopic healthy (Non-Hi-Myo-Healthy) eyes. DESIGN: Cross-sectional study. METHODS: After OCT radial B-scan, ONH imaging, Bruch's membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented in each B-scan and projected to BMO reference plane. The direction and magnitude of BMO/ASCO offset and BMO/SFO offset as well as the location and magnitude of ENC, EOCBT and ESF regions, perineural canal (pNC) retinal nerve fiber layer thickness (RNFLT) and pNC choroidal thickness (CT) were calculated within 30° sectors relative to the Foveal-BMO (FoBMO) axis. Hi-ESF eyes were defined to be those with an ESF region ≥100 µms in at least 1 sector. RESULTS: Hi-Myo eyes more frequently demonstrated Hi-ESF regions (87/122) than Non-Hi-myo-Healthy eyes (73/362) and contained significantly larger ENC, EOCBT, and ESF regions (P < .001) which were greatest in magnitude and prevalence within the inferior-temporal FoBMO sectors where Hi-Myo pNC-RNFLT and pNCCT were thinnest. BMO/ASCO offset and the BMO/SFO offset were both significantly increased (P < .001) in the Hi-Myo eyes, with the latter demonstrating a greater increase. CONCLUSIONS: ENC region tissue remodeling that includes the scleral flange is enhanced in Hi-Myo compared to Non-Hi-Myo-Healthy eyes. Longitudinal studies are necessary to determine whether the presence of an ENC region influences ONH susceptibility to aging and/or glaucoma.

Morphological and vascular evidence of glaucomatous damage in myopic guinea pigs with scleral crosslinking.

Guinea pigs are often used as models for myopia studies. However, the imaging structure and vasculature of the optic nerve head (ONH) in guinea pigs are tentative. This study investigated morphological parameters and vascular characteristics of the ONH in guinea pigs with form deprivation (FD) myopia before and after scleral crosslinking (CXL), using optical coherence tomography (OCT) and OCT angiography (OCTA). Refractive error, axial length (AL), intraocular pressure (IOP), and OCT-based structural parameters of the ONH were measured at baseline and 3 weeks after the FD + CXL procedure in guinea pigs. The 88 guinea pigs analysed in this study were aged 3 (n = 29), 4 (n = 51), and 5 (n = 8) weeks. The IOP, AL, average and vertical cup-to-disc ratio (C/D), circumpapillary retinal nerve fibre layer, disc area, and cup volume increased at 3 weeks compared to baseline values (all p < 0.001). The refractive error and rim area decreased at 3 weeks compared to baseline values (all p < 0.001). After adjustment for age, IOP was correlated positively with average C/D (p = 0.039) and negatively with rim area (p = 0.009). The severity of blood signal defects was positively associated with the average C/D at 3 weeks (p = 0.027). These findings may facilitate further research on myopia using guinea pigs.

OCT Optic Nerve Head Morphology in Myopia II: Peri-Neural Canal Scleral Bowing and Choroidal Thickness in High Myopia-An American Ophthalmological Society Thesis.

PURPOSE: To use optical coherence tomography (OCT) to characterize optic nerve head (ONH) peri-neural canal (pNC) scleral bowing (pNC-SB) and pNC choroidal thickness (pNC-CT) in 69 highly myopic and 138 healthy, age-matched, control eyes. DESIGN: Cross-sectional, case control study. METHODS: Within ONH radial B-scans, Bruch membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and pNC scleral surface were segmented. BMO and ASCO planes and centroids were determined. pNC-SB was characterized within 30° foveal-BMO (FoBMO) sectors by 2 parameters: pNC-SB-scleral slope (pNC-SB-SS), measured within 3 pNC segments (0-300, 300-700, and 700-1000 µm from the ASCO centroid); and pNC-SB-ASCO depth relative to a pNC scleral reference plane (pNC-SB-ASCOD). pNC-CT was calculated as the minimum distance between the scleral surface and BM at 3 pNC locations (300, 700, and 1100 µm from the ASCO). RESULTS: pNC-SB increased and pNC-CT decreased with axial length (P < .0133; P < .0001) and age (P < .0211; P < .0004) among all study eyes. pNC-SB was increased (P < .001) and pNC-CT was decreased (P < .0279) in the highly myopic compared to control eyes, and these differences were greatest in the inferior quadrant sectors (P < .0002). Sectoral pNC-SB was not related to sectoral pNC-CT in control eyes, but was inversely related to sectoral pNC-CT (P < .0001) in the highly myopic eyes. CONCLUSIONS: Our data suggest that pNC-SB is increased and pNC-CT is decreased in highly myopic eyes and that these phenomena are greatest in the inferior sectors. They support the hypothesis that sectors of maximum pNC-SB may predict sectors of greatest susceptibility to aging and glaucoma in future longitudinal studies of highly myopic eyes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Morphology of the optic nerve head and factors affecting it in the Northern Finland birth cohort.

PURPOSE: To assess topographic characteristics of the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) and study the effect of ocular and physiological factors on them in a middle-aged population. METHODS: A 1552-person randomised sample from Northern Finland population aged 45-49 was examined. Laser scanning tomography and optical coherency tomography were performed to obtain measurements for ONH and RNFL morphology. Measurements of the RNFL included global thickness and the six zones used in automated structure-function analysis (S-F analysis). Influence of central corneal thickness (CCT), refractive correction, intraocular pressure (IOP), anterior chamber angle, gender, blood pressure, height, weight and body mass index (BMI) on tomographic data was analysed. RESULTS: The optic disc area had a strong correlation with all other parameters of ONH morphology (R = 0.261 to 0.706) as did spherical equivalent (R = -0.280 to 0.280). The correlations between ONH and RNFL measurements were weaker (R = 0.057 to 0.180). Gender, CCT, anterior chamber angle, blood pressure, height and BMI had statistically significant, yet feeble, correlations with a number of ONH parameters. CONCLUSION: Other than spherical equivalent, the studied anatomical and physiological attributes had little predictive value on the ONH morphology. The optic disc area itself had a significant effect on other measurements of ONH tomography and should be taken into consideration when the thresholds for normal ONH morphology are calculated.

Antenatal and neonatal factors and morphology of the optic nerve head in the Northern Finland birth cohort.

PURPOSE: The optic nerve head (ONH) is a part of the brain that can be evaluated through the transparent medium of the eye. The purpose of this study was to explore the possible correlations among the properties of the optic nerve head, maternal factors during pregnancy and neonatal parameters in a randomized sample of a birth cohort. METHODS: The Northern Finland 1966 Birth Cohort has been prospectively monitored since their antenatal period. Data on pregnancy and neonatal period were collected during gestation and right after birth in 1966. A randomized sample of 3070 subjects underwent an ophthalmic assessment at the age of 46-48 years. The examination protocol included scanning laser ophthalmoscopy with the Heidelberg Retina Tomograph. The ophthalmological parameters assessed were the disc area and the neuroretinal rim volume of the ONH. RESULTS: We found that chronic pulmonary disease of the mother (p = 0.007), the number of gestational weeks (p = 0.030) and the mother's highest measured systolic blood pressure (p = 0.035) during pregnancy had a statistically significant effect on the disc area. Smaller disc size was associated with pulmonary disease and early gestation. There was a significant difference in rim volume between genders (p < 0.001). Women had larger neuroretinal rim volumes compared to men. CONCLUSION: In this population-based study, the vast majority of antenatal and neonatal factors showed no correlation with optic disc area or rim volume. Furthermore, even the factors with statistically significant correlation with ONH morphology had limited predictive value.

Thinner peripapillary retinal nerve fibre layer and macular retinal thickness in adolescents with surgically treated hydrocephalus in infancy.

PURPOSE: To map the morphology of the retina and optic disc in adolescents with surgically treated hydrocephalus (HC) in infancy and to compare the results with healthy controls. METHODS: The study comprised 26 adolescents (16 male, mean age 15 years) with HC and 31 sex- and aged-matched controls. The following optical coherence tomography (OCT) parameters were obtained: macular retinal thickness (MRT) and volume (MRV), thickness of the macular and peripapillary retinal nerve fibre layer (ppRNFL), and area of the optic disc, cup and rim. RESULTS: The MRT was thinner amongst those with HC compared with controls (right eye (RE) 262.2 ± 15.3 and 275.8 ± 15.1 µm; p = 0.0051), and the MRV was smaller (RE 7.37 ± 0.36 and 7.83 ± 0.35 mm3 ; p = 0.0002). The HC group showed a thinner ppRNFL (RE 88.3 ± 14.9 and 103.5 ± 8.1 µm; p = 0.0002) but a thicker central macular RNFL (RE 11.6 ± 10.4 and 2.07 ± 3.00 µm; p = <0.0001) and foveal minimum (RE 211.1 ± 32.0 and 186.3 ± 15.9 µm; p = 0.0013). Optic disc variables showed no difference between groups. Correlations were found in the HC group between best corrected visual acuity (expressed in logMAR) and ppRNFL (RE r = -0.56, p = 0.018), and disc area (RE r = -0.52, p = 0.033). CONCLUSION: Thinner ppRNFL and MRT and smaller MRV were found in adolescents with surgically treated HC in infancy compared with controls. In contrast, the central macular RNFL and foveal minimum were thicker. Further studies are required to evaluate the diagnostic value of OCT to indicate increased intracranial pressure timely and follow-up in individuals with surgically treated HC.

Macula and optic disk features in methamphetamine and crystal methamphetamine addicts using optical coherence tomography.

PURPOSE: Methamphetamine and crystal methamphetamine abusers were compared with healthy subjects using optical coherence tomography to assess their retinal nerve fiber layer, macula, and optic disk characteristics. METHODS: Forty-one methamphetamine and crystal methamphetamine abusers and 42 healthy subjects (mean ± SD of age: 35.82 ± 8.6 and 37.76 ± 9.1 years, respectively) were incorporated in this cross-sectional study. The drug abusers had a history of at least five years of substance use through smoking. Fourier-domain optical coherence tomography was used to image and assess the characteristics of retinal nerve fiber layer, macular thickness, and optic disk in the study groups. RESULTS: The retinal nerve fiber layer thickness was significantly lower in the superior and temporal retinal quadrants of drug abusers than healthy subjects (P = 0.008 and P = 0.028, respectively). This study did not find a significant difference between drug abusers and healthy controls regarding optic to disk ratio, rim area, and disk area (P > 0.05). The comparison between the study groups showed that the reductions in perifovea and the superior quadrant of parafoveal thickness were statistically significant (P < 0.001 and P = 0.029, respectively). CONCLUSION: Fourier-domain optical coherence tomography measurements showed that the retinal nerve fiber layer and macular thickness were different between methamphetamine and crystal methamphetamine abusers and healthy subjects, which should be considered in clinical practice. It seems that these drug abuses can cause alterations in retinal morphology.

Large-scale machine-learning-based phenotyping significantly improves genomic discovery for optic nerve head morphology.

Genome-wide association studies (GWASs) require accurate cohort phenotyping, but expert labeling can be costly, time intensive, and variable. Here, we develop a machine learning (ML) model to predict glaucomatous optic nerve head features from color fundus photographs. We used the model to predict vertical cup-to-disc ratio (VCDR), a diagnostic parameter and cardinal endophenotype for glaucoma, in 65,680 Europeans in the UK Biobank (UKB). A GWAS of ML-based VCDR identified 299 independent genome-wide significant (GWS; p ≤ 5 × 10-8) hits in 156 loci. The ML-based GWAS replicated 62 of 65 GWS loci from a recent VCDR GWAS in the UKB for which two ophthalmologists manually labeled images for 67,040 Europeans. The ML-based GWAS also identified 93 novel loci, significantly expanding our understanding of the genetic etiologies of glaucoma and VCDR. Pathway analyses support the biological significance of the novel hits to VCDR: select loci near genes involved in neuronal and synaptic biology or harboring variants are known to cause severe Mendelian ophthalmic disease. Finally, the ML-based GWAS results significantly improve polygenic prediction of VCDR and primary open-angle glaucoma in the independent EPIC-Norfolk cohort.

Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies.

Histologic validation of optical coherence tomography-based three-dimensional morphometric measurements of the human optic nerve head: Methodology and preliminary results.

PURPOSE: To compare the three-dimensional (3D) morphology of the deep load-bearing structures of the human optic nerve head (ONH) as revealed in vivo by spectral domain optical coherence tomography (SDOCT) with ex vivo quantitative 3D histology. METHODS: SDOCT imaging of the ONH was performed in six eyes from three brain-dead organ donors on life-support equipment awaiting organ procurement (in vivo conditions). Following organ procurement (ex vivo conditions), the eyes were enucleated and underwent a pars plana vitrectomy followed by pressurization to physiologic IOP and immersion fixation. Ex vivo ONH morphology was obtained from high-fidelity episcopic fluorescent 3D reconstruction. Morphologic parameters of the observed ONH canal geometry and peripapillary choroid, as well as the shape, visibility and depth of the lamina cribrosa were compared between ex vivo and in vivo measurements using custom software to align, scale, and manually delineate the different regions of the ONH. RESULTS: There was significant correspondence between in vivo and ex vivo measurements of the depth and shape of the lamina cribrosa, along with the size and shape of Bruch's membrane opening (BMO) and anterior scleral canal opening (ASCO). Weaker correspondence was observed for choroidal thickness; as expected, a thinner choroid was seen ex vivo due to loss of blood volume upon enucleation (-79.9%, p < 0.001). In addition, the lamina was shallower (-32.3%, p = 0.0019) and BMO was smaller ex vivo (-3.38%, p = 0.026), suggesting post mortem shrinkage of the fixed tissue. On average, while highly variable, only 31% of the anterior laminar surface was visible in vivo with SDOCT (p < 0.001). CONCLUSIONS: Morphologic parameters by SDOCT imaging of the deep ONH showed promising correspondence to histology metrics. Small but significant shrinkage artifact, along with large effects of exsanguination of the choroid, was seen in the ex vivo reconstructions of fixed tissues that may impact the quantification of ex vivo histoarchitecture, and this should be considered when developing models and biomarkers based on ex vivo imaging of fixed tissue. Lack of visibly of most of the lamina surface in SDOCT images is an important limitation to metrics and biomarkers based on in vivo images of the ONH deep tissues.

Regional Differences and Physiologic Behaviors in Peripapillary Scleral Fibroblasts.

Purpose: The purpose of this study was to describe the cellular architecture of normal human peripapillary sclera (PPS) and evaluate surface topography's role in fibroblast behavior. Methods: PPS cryosections from nonglaucomatous eyes were labelled for nuclei, fibrillar actin (FA), and alpha smooth muscle actin (αSMA) and imaged. Collagen fibrils were imaged using second harmonic generation. Nuclear density and aspect ratio of the internal PPS (iPPS), outer PPS (oPPS), and peripheral sclera were determined. FA and αSMA fibril alignment with collagen extracellular matrix (ECM) was determined. PPS fibroblasts were cultured on smooth or patterned membranes under mechanical strain and in the presence of TGFß1 and 2. Results: The iPPS (7.1 ± 2.0 × 10-4, P < 0.0001) and oPPS (5.3 ± 1.4 × 10-4, P = 0.0013) had greater nuclei density (nuclei/µm2) than peripheral sclera (2.5 ± 0.8 × 10-4). The iPPS (2.0 ± 0.3, P = 0.002) but not oPPS (2.4 ± 0.4, P = 0.45) nuclei had smaller aspect ratios than peripheral (2.7 ± 0.5) nuclei. FA was present throughout the scleral stroma and was more aligned with oPPS collagen (9.6 ± 1.9 degrees) than in the peripheral sclera (15.9 ± 3.9 degrees, P =0.002). The αSMA fibers in the peripheral sclera were less aligned with collagen fibrils (26.4 ± 4.8 degrees) than were FA (15.9 ± 3.9 degrees, P = 0.0002). PPS fibroblasts cultured on smooth membranes shifted to an orientation perpendicular to the direction of cyclic uniaxial strain (1 Hz, 5% strain, 42.2 ± 7.1 degrees versus 62.0 ± 8.5 degrees, P < 0.0001), whereas aligned fibroblasts on patterned membranes were resistant to strain-induced reorientation (5.9 ± 1.4 degrees versus 10 ± 3.3 degrees, P = 0.21). Resistance to re-orientation was reduced by TGFß treatment (10 ± 3.3 degrees without TGFß1 compared to 23.1 ± 4.5 degrees with TGFß1, P < 0.0001). Conclusions: Regions of the posterior sclera differ in cellular density and nuclear morphology. Topography alters the cellular response to mechanical strain.

Location of Parapapillary Gamma Zone and Vertical Fovea Location. The Beijing Eye Study 2011.

Purpose: To assess the spatial relationship between the locations of the parapapillary gamma zone and the fovea. Methods: In a non-glaucomatous subgroup of the population-based Beijing Eye Study population, we measured the mean angle between the optic disc-fovea line and the horizontal (disc-fovea angle), the vertical distance of the fovea from the horizontal through the optic disc center (fovea vertical distance), and the location and width of the widest part of parapapillary gamma zone. Results: The study included 203 individuals (203 eyes; mean axial length, 24.4 ± 1.5 mm; range, 22.03-28.87 mm). The widest gamma zone part was located most often temporal horizontally (51.7%), then inferiorly (43.8%), superiorly (2.5%), and nasally (2.0%). The disc-fovea angle (mean, 7.50° ± 4.00°; range, -6.30° to -23.25°) was significantly higher (P = 0.003; i.e., fovea located more inferiorly) in eyes with the widest gamma zone inferiorly (8.46° ± 4.37°) than in eyes with the widest gamma zone temporally (6.71° ± 3.46°) and in eyes with the widest gamma zone temporally, superiorly, or nasally combined (6.75° ± 3.53°; P = 0.003). The fovea vertical distance (mean, 0.65 ± 0.33 mm; range, -0.20 to 1.67 mm) was longer (P = 0.001; i.e., fovea located more inferiorly) in eyes with the widest gamma zone inferiorly (0.73 ± 0.33 mm) than in eyes with the widest gamma zone temporally (0.58 ± 0.30 mm) and in eyes with a temporal, superior, or nasal gamma zone combined (0.58 ± 0.31 mm; P = 0.001). The fovea vertical distance increased (multivariate analysis) with the widest gamma zone location inferiorly (ß = 0.25; P = 0.001) and wider width of the gamma zone (ß = 0.19; P = 0.01). Conclusions: An inferior fovea location is associated with a wider inferior gamma zone and vice versa, supporting the notion of an inferior shifting of Bruch's membrane as the cause for an inferior gamma zone.

ISNT rule satisfaction in Korean non-glaucomatous subjects.

PURPOSE: To evaluate the efficacy of the ISNT rule in normal eyes of Koreans. METHODS: We retrospectively reviewed medical records of 890 subjects with fundus photographs and evaluated the presence of the cup and ISNT rule satisfaction. If the ISNT rule was violated, the quadrants in which the neuroretinal rim was thinnest and thickest, respectively, were evaluated. RESULTS: Among 890 eyes, 84.7% showed the cup. The subjects without the cup were significantly younger and more hyperopic. Among 754 eyes with the cup, 53.5% showed ISNT rule satisfaction. In 351 eyes violating the ISNT rule, the most common quadrant showing the thickest neuroretinal rim was the inferior (65.5%), and the thinnest, the temporal (98.3%). CONCLUSION: The cup was absent in 15% of the assessed eyes. Only about half of eyes with the cup showed ISNT rule satisfaction. Even in eyes violating ISNT rule, the inferior was the most common quadrant with the thickest neuroretinal rim and the temporal, the thinnest.

Optic Nerve Head Morphological Changes Over 12 Hours in Seated and Head-Down Tilt Postures.

Purpose: The purpose of this study was to determine changes in optic nerve head (ONH) morphology in seated and 6° head-down tilt (HDT) postures over a 12-hour period. Methods: Thirty eyes of 30 healthy human subjects (15 females) were included. Composite radial and circular optical coherence tomography (OCT) scans centered on the ONH, intraocular pressure (IOP), and optic nerve sheath diameter (ONSD) were acquired every two hours from 7 a.m. to 7 p.m. for both seated (n = 30) and HDT (n = 10) sessions. Global minimum rim width (BMO-MRW), total retinal thickness (TRT), retinal nerve fiber layer thickness (RNFLT), and Bruch's membrane opening (BMO) height were quantified. Results: BMO-MRW decreased an average of 9.55 ± 8.03 µm (P < 0.01) over 12 hours in a seated position (range, -26.64 to +3.36 µm), and thinning was greater in females (-13.56 vs. -5.55 µm, P = 0.004). Modest decreases in TRT from the BMO to 500 µm (P < 0.04) and RNFLT for the 2.7, 3.5, and 4.2 mm circular scans (P < 0.02) were also observed. BMO-MRW thinning was not related to changes in IOP or ONSD (P = 0.34). In HDT, IOP and ONSD increased, BMO height moved anteriorly, and BMO-MRW thinning did not occur (P > 0.1). Conclusions: The neuroretinal rim thins throughout the day in healthy individuals, and this change cannot be explained by changes in IOP or ONSD during the same time period. A HDT posture blunts the neuroretinal rim thinning observed in a seated position, suggesting a role of the translaminar pressure difference.

Analyzing a putative enhancer of optic disc morphology.

BACKGROUND: Genome-wide association studies have identified the CDC7-TGFBR3 intergenic region on chromosome 1 to be strongly associated with optic disc area size. The mechanism of its function remained unclear until new data on eQTL markers emerged from the Genotype-Tissue Expression project. The target region was found to contain a strong silencer of the distal (800 kb) Transcription Factor (TF) gene GFI1 (Growth Factor Independent Transcription Repressor 1) specifically in neuroendocrine cells (pituitary gland). GFI1 has also been reported to be involved in the development of sensory neurons and hematopoiesis. Therefore, GFI1, being a developmental gene, is likely to affect optic disc area size by altering the expression of the associated genes via long-range interactions. RESULTS: Distribution of haplotypes in the putative enhancer region has been assessed using the data on four continental supergroups generated by the 1000 Genomes Project. The East Asian (EAS) populations were shown to manifest a highly homogenous unimodal haplotype distribution pattern within the region with the major haplotype occurring with the frequency of 0.9. Another European specific haplotype was observed with the frequency of 0.21. The major haplotype appears to be involved in silencing GFI1repressor gene expression, which might be the cause of increased optic disc area characteristic of the EAS populations. The enhancer/eQTL region overlaps AluJo element, which implies that this particular regulatory element is primate-specific and confined to few tissues. CONCLUSION: Population specific distribution of GFI1 enhancer alleles may predispose certain ethnic groups to glaucoma.

Inner retinal thickness and optic disc measurements in obese children and adolescents.

PURPOSE: This study aimed to evaluate optic nerve head parameters and inner retinal layer thicknesses in obese children and adolescents. METHODS: Forty-one eyes of 41 pediatric obese participants and 41 eyes of 41 age- and sex-matched healthy controls were included in this study. Body mass index was calculated, based on sex and age, using body weight and height measurements. Blood lipid values (i.e., cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride) were measured in obese participants. Optical coherence tomography was used to examine optic nerve head parameters, including rim area, disc area, cup-to-disc ratio, and cup volume, as well as the thicknesses of retinal nerve fiber layers and macular ganglion cell-inner plexiform layers. RESULTS: Optic disc parameters were similar in obese and healthy children (p>0.05). The percentage of binocular retinal nerve fiber layer thickness symmetry was significantly different between obese and control groups (p=0.003). Compared to the control group, participants in the obese group exhibited thinner retinal nerve fiber layers in the superior quadrants (p=0.04) and thinner ganglion cell-inner plexiform layers in the superior-temporal sectors (p=0.04). There were no statistically significant correlations between the ocular parameters and lipid blood test values assessed in this study (p>0.05). Body mass index was significantly negatively correlated with the mean retinal nerve fiber layer thickness (r=-0.33, p=0.03) in the obese group. There was no significant correlation between intraocular pressure and body mass index (r=0.05, p=0.74). CONCLUSION: Compared to healthy children, obese children had greater binocular retinal nerve fiber layer thickness asymmetry and thinner retinal nerve fiber and ganglion cell-inner plexiform layers in several sectors. Blood lipid levels were not associated with retinal thickness or optic disc parameters in obese children.

Inner retinal thickness and optic disc measurements in obese children and adolescents / Espessura retiniana interna e medidas do disco óptico na obesidade pediátrica

ABSTRACT Purpose: This study aimed to evaluate optic nerve head parameters and inner retinal layer thicknesses in obese children and adolescents. Methods: Forty-one eyes of 41 pediatric obese participants and 41 eyes of 41 age- and sex-matched healthy controls were included in this study. Body mass index was calculated, based on sex and age, using body weight and height measurements. Blood lipid values (i.e., cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride) were measured in obese participants. Optical coherence tomography was used to examine optic nerve head parameters, including rim area, disc area, cup-to-disc ratio, and cup volume, as well as the thicknesses of retinal nerve fiber layers and macular ganglion cell-inner plexiform layers. Results: Optic disc parameters were similar in obese and healthy children (p>0.05). The percentage of binocular retinal nerve fiber layer thickness symmetry was significantly different between obese and control groups (p=0.003). Compared to the control group, participants in the obese group exhibited thinner retinal nerve fiber layers in the superior quadrants (p=0.04) and thinner ganglion cell-inner plexiform layers in the superior-temporal sectors (p=0.04). There were no statistically significant correlations between the ocular parameters and lipid blood test values assessed in this study (p>0.05). Body mass index was significantly negatively correlated with the mean retinal nerve fiber layer thickness (r=-0.33, p=0.03) in the obese group. There was no significant correlation between intraocular pressure and body mass index (r=0.05, p=0.74). Conclusion: Compared to healthy children, obese children had greater binocular retinal nerve fiber layer thickness asymmetry and thinner retinal nerve fiber and ganglion cell-inner plexiform layers in several sectors. Blood lipid levels were not associated with retinal thickness or optic disc parameters in obese children.

RESUMO Objetivo: O objetivo deste estudo foi avaliar os parâmetros da cabeça do nervo óptico e a espessura da camada interna da retina em crianças e adolescentes obesos. Métodos: Quarenta e um olhos de 41 participantes pediátricos obesos e 41 olhos de 41 controles saudáveis pareados por idade e sexo foram incluídos neste estudo. O índice de massa corporal foi calculado com base no sexo e na idade, utilizando medidas de peso e estatura corporal. Os valores de lipídios no sangue (colesterol, lipoproteína de baixa e alta densidade e triglicérides) foram medidos nos participantes obesos. A tomografia de coerência óptica foi usada para examinar os parâmetros da cabeça do nervo óptico, incluindo a área da borda, área do disco, razão escavação/disco, volume da escavação, espessura s camadas de fibra nervosa da retina e as camadas plexiformes internas das células ganglionares da mácula. Resultados: Os parâmetros do disco óptico foram semelhantes em crianças obesas e saudáveis (p>0,05). A porcentagem da simetria da espessura da camada de fibras nervosas da retina binocular foi significativamente diferente entre os grupos obesos e controle (p=0,003). Comparados ao grupo controle, os participantes do grupo obeso exibiram camadas mais finas de fibras nervosas da retina nos quadrantes superiores (p=0,04) e camadas plexiformes mais finas da célula ganglionar interna nos setores temporal superior (p=0,04). Não houve correlação significante entre os parâmetros oculares e os valores dos exames de sangue lipídico avaliados neste estudo (p>0,05). O índice de massa corporal foi significativamente correlacionado negativamente com a espessura média da camada de fibras nervosas da retina (r=-0,33, p=0,03) no grupo obeso. Não houve correlação significativa entre a pressão intraocular e o índice de massa corporal (r=0,05, p=0,74). Conclusão: Comparadas às crianças saudáveis, as crianças obe sas apresentaram maior assimetria binocular na espessura da ca mada de fibras nervosas da retina e fibras nervosas da retina mais finas e camadas plexiformes internas das células ganglionares em vários setores. Os níveis de lipídios no sangue não foram associados à espessura da retina ou aos parâmetros do disco óptico em crianças obesas.

A 3D model to evaluate retinal nerve fiber layer thickness deviations caused by the displacement of optical coherence tomography circular scans in cynomolgus monkeys (Macaca fascicularis).

The main objective of the study was to analyze deviations in retinal nerve fiber layer (RNFL) thickness measurements caused by the displacement of circular optic disc optical coherence tomography scans. High-density radial scans of the optic nerve heads of cynomolgus monkeys were acquired. The retinal nerve fiber layer was manually segmented, and a surface plot of the discrete coordinates was generated. From this plot, the RNFL thicknesses were calculated and compared between accurately centered and intentionally displaced circle scans. Circle scan displacement caused circumpapillary retinal nerve fiber layer thickness deviations of increasing magnitude with increasing center offset. As opposed to the human eye, horizontal displacement resulted in larger RNFL thickness deviations than vertical displacement in cynomolgus monkeys. Acquisition of high-density radial scans allowed for the mathematical reconstruction and modelling of the nerve fiber layer and extrapolation of its thickness. Accurate and strictly repeatable circle scan placement is critical to obtain reproducible values, which is essential for longitudinal studies.