Normal Optic Nerve Head Research Articles

Central retinal vessel trunk exit location: An important factor while evaluating the neuroretinal rim.

Optic nerve head (ONH) evaluation plays a key role in differentiating normal from glaucomatous disk. Thinning of the inferior neuroretinal rim (NRR) has been noted in early glaucoma. However, NRR thickness in different quadrants appears to depend on various factors including central retinal vessel trunk exit (CRVT) position. We evaluated ocular parameters that determined the NRR thickness in the different quadrants of normal eyes. Retrospective review of demographic and ocular data from 773 eyes of 388 subjects with normal ONH over one year was undertaken. Nearly 54% were males, and the mean age was 43.2 years. The CRVT exit was central in 50% (773). The common site for noncentral CRVT was superotemporal (ST) [37%, 141/384] followed by inferotemporal (IT) [35%, 135/384]. With noncentral CRVT, the probability that the inferior, superior, nasal and temporal (ISNT) rule was not followed was 1.42 times ( P < 0.001). The thinnest rim quadrant (TRQ) was mostly ST (69%) irrespective of CRVT location. The TRQ was IT in 40% when CRVT was noncentral and 82% with IT CRVT exit. With noncentral CRVT, round disks favored noncompliance [132 (54.1%), odds ratio (OR) 2.56] with the ISNT rule. The OR of noncompliance with the ISNT rule increases 1.89 times with inferonasal CRVT and 1.22 times with a unit increase in the axial length. TRQ was IT in IT CRVT, and noncompliance with the ISNT rule was observed with large disks, longer axial length, and noncentral CRVT. This implies that despite the ISNT rule being violated these eyes do not have optic nerve pathology and should not be subjected to unnecessary diagnostic tests.

Artificial intelligence in glaucoma detection using color fundus photographs.

To explore the potential of artificial intelligence (AI) for glaucoma detection using deep learning algorithm and evaluate its accuracy for image classification of glaucomatous optic neuropathy (GON) from color fundus photographs. A total of 1375 color fundus photographs, 735 normal optic nerve head and 640 GON, were uploaded on the AI software for training, validation, and testing using deep learning model, which is based on Residual Network (Res Net) 50V2. For initial training and validation, 400 fundus images (200 normal and 200 GON) were uploaded and for the final training and testing 975 (535 normal and 440 GON) were uploaded later. Accuracy, sensitivity, and specificity were used to evaluate the image classification performance of the algorithm. Also, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated. The model used in the study showed an image classification accuracy of 81.3%, sensitivity of 83%, and specificity of 80% for the detection of GON. The false-negative grading was 17% and false-positive grading was 20% for the image classification of GON. Coexistence of glaucoma in patients with high myopia, early glaucoma in a small disc, and software misclassification of GON were the reasons for false-negative results. Physiological large cupping in a large disc, myopic or titled disc, and software misclassification of normal optic disc were the reasons for false-positive results. The model employed in this study achieved a good accuracy, and hence has a good potential in detection of GON using color fundus photographs.

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

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. 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. 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. 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.

Astrocyte responses to experimental glaucoma in mouse optic nerve head.

PurposeTo delineate responses of optic nerve head astrocytes to sustained intraocular pressure (IOP) elevation in mice.MethodsWe elevated IOP for 1 day to 6 weeks by intracameral microbead injection in 4 strains of mice. Astrocyte alterations were studied by transmission electron microscopy (TEM) including immunogold molecular localization, and by laser scanning microscopy (LSM) with immunofluorescence for integrin β1, α-dystroglycan, and glial fibrillary acidic protein (GFAP). Astrocyte proliferation and apoptosis were quantified by Ki67 and TUNEL labeling, respectively.ResultsAstrocytes in normal optic nerve head expressed integrin β1 and α-dystroglycan by LSM and TEM immunogold labeling at electron dense junctional complexes that were found only on cell membrane zones bordering their basement membranes (BM) at the peripapillary sclera (PPS) and optic nerve head capillaries. At 1–3 days after IOP elevation, abnormal extracellular spaces appeared between astrocytes near PPS, and axonal vesical and mitochondrial accumulation indicated axonal transport blockade. By 1 week, abnormal spaces increased, new collagen formation occurred, and astrocytes separated from their BM, leaving cell membrane fragments. Electron dense junctional complexes separated or were absent at the BM. Astrocyte proliferation was modest during the first week, while only occasional apoptotic astrocytes were observed by TEM and TUNEL.ConclusionsAstrocytes normally exhibit junctions with their BM which are disrupted by extended IOP elevation. Responses include reorientation of cell processes, new collagen formation, and cell proliferation.

Optic Nerve Head Volumetry by Optical Coherence Tomography in Papilledema Related to Idiopathic Intracranial Hypertension.

PurposeIdiopathic intracranial hypertension (IIH) leads to optic nerve head swelling and optic atrophy if left untreated. We wanted to assess an easy to perform volumetric algorithm to detect and quantify papilledema in comparison to retinal nerve fiber layer (RNFL) analysis using optical coherence tomography (OCT).MethodsParticipants with and without IIH underwent visual acuity testing at different contrast levels and static perimetry. Spectralis-OCT measurements comprised standard imaging of the peripapillary RNFL and macular ganglion cell layer (GCL). The optic nerve head volume (ONHV) was determined using the standard segmentation software and the 3.45 mm early treatment diabetic retinopathy study (ETDRS) grid, necessitating manual correction within Bruch membrane opening. Three neuro-ophthalmologists graded fundus images according to the Frisén scale. A mixed linear model (MLM) was used to determine differences between study groups. Sensitivity and specificity was evaluated using the area under the receiver-operating characteristic (ROC).ResultsTwenty-one patients with IIH had an increased ONHV of 6.46 ± 2.36 mm3 as compared to 25 controls with 3.20 ± 0.25 mm3 (P < 0.001). The ONHV cutoff distinguishing IIH from controls was 3.97 mm3 (i.e. no patient with IIH had an ONHV below and no healthy individual above this value). The area under the curve (AUC) for ONHV was 0.99 and for the RNFL at 3.5 mm 0.90. The Frisén scale grading correlated higher with the ONHV (r = 0.90) than with the RNFL thickness (r = 0.68). ONHV measurements were highly reproducible in both groups (coefficient of variation <0.01%).ConclusionsOCT-based volumetry of the optic nerve head discriminates very accurately between individuals with and without IIH. It may serve as a useful adjunct to the rating with the subjective and ordinal Frisén scale.Translational RelevanceA simple OCT protocol run on the proprietary software of a commercial OCT device can reliably discriminate between normal optic nerve heads or pseudo-papilledema and true papilledema while being highly reproducible. Our normative data and OCT preset may be used in further clinical studies.

The Morphological Description Automation of the Optic Nerve Head Boundary in Digital Fundus Images

Purpose. To develop the automating method for the description of the optic nerve head condition. The method allows to differentiate the optic nerve head with clear boundaries typical for the normal fundus and optic nerve head with blurred boundaries typical for different types of ophthalmopathology. Methods. The proposed method is based on integration algorithm of luminance samples along the diagonal. It shows that optic nerve head images with blurred boundaries are characterized by a more linear increase in brightness in the frontal region compared to the accumulation result for the case of normal optic nerve head. To identify this feature the firstorder derivative can be used. To reduce the effect of blood vessels on the result of processing luminance samples along the diagonal is performed in the red channel since the blood vessels effect on the optic nerve head border is minimized in the red color component. Results. The application of this method to images of optic nerve head with diffuse boundaries shows that the accumulation result is characterized by a slower brightness variation. Тhe analysis of 20 fundus images revealed that the value of the first-order derivative of the result of accumulation of luminance readings diagonally for images of optic nerve head with blurred boundaries is 2 times smaller than for images of optic nerve head with clear boundaries. Conclusions. Тhe presented method can be used to create expert systems which allow to automate the process of morphological description of the optic nerve head border from the fundus images and also can partially solve the diagnostic problem. Since the disappearance of the clarity of the optic nerve head borders and the appearance of their blurring are the main diagnostic criterions for various types of pathology this method can be used to create medical expert systems and software for the fundus images processing.

Comparison of Anterior Segment Optical Coherence Tomography Parameters Among Vietnamese, Chinese, and Whites

To evaluate the difference in anterior segment optical coherence tomography (AS-OCT) parameters among ethnic Vietnamese, Chinese, and whites. Cross-sectional study. We prospectively recruited phakic nonglaucomatous participants (based on intraocular pressure <21mm Hg, normal optic nerve head and retinal nerve fiber, and cup-to-disc ratio < 0.6) of 3 ethnic groups-Vietnamese, Chinese, and white. AS-OCT parameters including angle (angle opening distance, trabecular-iris space area, and angle recess area), iris (iris thickness, iris area, and iris curvature [Icurv]), and anterior chamber parameters (anterior chamber depth, width [ACW], area, and lens vault [LV]) were obtained. A linear regression model with adjustment for age, sex, axial length, and pupillary diameter was used for analysis. Subgroup analysis was performed in closed- and open-angle subgroups, which were defined in eyes with gonioscopically visible posterior trabecular meshwork for less than 2 quadrants (closed) and equal to or more than 2 quadrants (open). Data were obtained from 126 Vietnamese, 124 Chinese, and 112 white participants. Mean (standard deviation) age of participants was 60.2 (11.8) years. Among overall subjects, Vietnamese had significantly smaller values in all angle and anterior chamber parameters than Chinese and white subjects (all P ≤ .001) except LV. Vietnamese had significantly higher Icurv than Chinese (B-0.065, P < .001) and white subjects (B-0.073, P < .001). In the open-angle subgroup, Vietnamese had significantly smaller angle and anterior chamber dimensions (P ≤ .001) and thicker iris (P < .001) than whites, whereas there was no significant difference in all parameters compared to Chinese except for smaller ACW in Vietnamese (P < .001). In the closed-angle subgroup, Vietnamese possessed smaller angle, smaller anterior chamber dimensions, and higher Icurv than Chinese and white subjects (P < .001). Vietnamese had significantly greater LV compared to Chinese (B-204.8, P= .001). Vietnamese subjects had more of the anatomic characteristics associated with risk for angle closure, including small anterior chamber dimension, high iris curvature, and high lens vault, compared to the other 2 ethnicities.

Vessel density in OCT angiography permits differentiation between normal and glaucomatous optic nerve heads.

To evaluate whether optical coherence tomography angiography (OCTA) can detect altered vessel density (VD) at the optic nerve head (ONH) in glaucoma patients. Special attention is paid to the accuracy of the OCTA technique for distinguishing healthy from glaucomatous eyes. A total of 171 eyes were examined by the OCTA system AngioVue™ (Optovue): 97 eyes diagnosed with glaucoma and 74 healthy control eyes. The papillary and peripapillary VD was measured. Furthermore, the VD was correlated with different structural and functional measurements. In order to test the accuracy of differentiation between eyes with and without glaucoma, we calculated the receiver operating characteristic curve (ROC) and the area under the curve (AUC). The papillary and peripapillary VD in glaucomatous eyes was significantly lower than in healthy eyes (P<0.05). The VD of the nasal peripapillary sector was significantly lower than in the other sectors. The further the disease had progressed [measured by determining the thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL)] the greater the VD reduction. The AUC discriminated well between glaucomatous and normal eyes (consensus classifier 94.2%). OCTA allows non-invasive quantification of the peripapillary and papillary VD, which is significantly reduced in glaucomatous eyes and accurately distinguishes between healthy and diseased eyes. OCTA expands the spectrum of procedures for detecting and monitoring glaucoma.

Optical coherence tomography angiography of the optic nerve head, current situation and future perspective

The circulation of the optic nerve head is derived from two sources; the prelaminar, laminar and retrolaminar circulation are mainly arise from the posterior ciliary artery circulation, whereas the nerve fiber layer over the optic disc is fed by central retinal artery (1,2). A variety of optic neuropathies with ischemic, glaucomatous, inflammatory and hereditary etiologies may affect the optic disc circulation (1,2). Several imaging techniques have been developed for the in vivo measurement of ocular blood flow. Dynamic angiography using intravenous injection of a fluorescent dye has been the mainstay for the evaluation of the normal optic nerve head vasculature and for the in vivo diagnosis and management of the optic neuropathies for several decades (2,3). Other imaging modalities including laser Doppler velocimetry, laser Doppler flowmetry, color Doppler ultrasound imaging, and spectral-domain optical coherence tomography have been used to assess various aspects of the optic nerve head circulation (3,4). These imaging modalities suffer from limitations such as invasiveness, lack of precision, low spatial resolution, high cost and different types of artifacts.

Retinal and optic nerve abnormalities in neurodegeneration associated with mutations in C19orf12 (MPAN)

BackgroundMitochondrial membrane protein-associated neurodegeneration (MPAN) is an neurodegeneration with brain iron accumulation (NBIA) subtype with mutation of C19orf12. Optic atrophy is one of the core symptoms in almost all MPAN cases, but the detailed ophthalmologic features of MPAN patients have not yet been described. MethodsAll consecutive symptomatic, gene proven MPAN patients underwent a detailed ophthalmological examination: best corrected visual acuity (BCVA), slit lamp examination, dilated fundus examination, tonometry, optical coherent tomography (OCT) and electrophysiological examinations. The total thickness of the macula (Mth) and the retinal nerve fiber layer (RNFL) were measured separately. ResultsSix males aged 18 to 21years were examined. Dilated fundus examination revealed complete optic disc paleness in 5 patients. In all patients, the Mth was normal. The total RNFL was thin in five patients. The latencies of PVEP were prolonged in all patients except one. In all cases, the ERG latencies and amplitudes were normal under both scotopic and photopic conditions. One patient, carrying different mutation and with different disease course, had a normal optic nerve head, normal RNFL thickness and PVEP latencies. ConclusionsOptic nerve atrophy seems to be genotype-dependent in MPAN patients but is typical for the disease. This phenomenon, together with normal ERG examination, is most distinctive for MPAN.

What is a typical optic nerve head?

Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.

Visual Pathways in Humans With Ephrin-B1 Deficiency Associated With the Cranio-Fronto-Nasal Syndrome.

Numerous animal studies demonstrated the importance of components of the ephrin/Eph system for correct visual system development. Analogous investigations in humans are entirely missing. Here, we examined the visual system in humans with ephrin-B1 deficiency, which is x-linked and associated with the cranio-fronto-nasal syndrome (CFNS) in heterozygous females. For one male hemizygous for ephrin-B1 deficiency and three affected heterozygous females with molecular-genetically confirmed mutations, the integrity of the partial decussation of the optic nerves was assessed with visual evoked potentials (VEPs) and compared with albinotic, achiasmic, and control participants with healthy vision. Further, retinal morphology and function and the gross-retinotopic representation of the primary visual cortex were examined with spectral-domain optical coherence tomography (SD-OCT), ERG, and multifocal (mf) VEPs for the male participant and part of the carriers. Strabismus and lack of stereovision was evident in the male and two of the females. Other characteristics of the visual system organization and function were normal: (1) retina: SD-OCT and funduscopy indicated normal foveal and optic nerve head morphology. Electroretinograms indicated normal retinal function, (2) optic chiasm: conventional (c)VEP showed no evidence for misrouting and mfVEPs were only suggestive of, if any, very minor local misrouting, and (3) visual cortex: mfVEP characteristics indicated normal retinotopic gross-representations of the contralateral visual hemifield in each hemisphere. While ephrin-B1 deficiency leads to abnormal visual pathways in mice, it leaves the human visual system, apart from deficits in binocular vision, largely normal. We presume that other components of the ephrin-system can substitute the lack of ephrin-B1 in humans.

Establishing new OCT parameters: Is race‐specific phenotyping necessary?

SummaryEstablishing phenotypes of the normal optic nerve head via normative databases is vitally important for clinicians. Attributing likelihoods for glaucoma based on single OCT examinations helps clinicians triage and assign resources for further or more intensive testing. It is recognized that significant race‐specific differences in optic nerve head parameters exist, however, it their utility has not improved diagnostics. One reason could be that these databases have thus far used only conventional parameters that do not exploit measurements now possible to characterize neuroretinal rim parameters that are anatomically and geometrically accurate, or the deep optic nerve head. This presentation will review the literature on race‐specific databases, postulate reasons for their inability to yield better diagnostics and present new alternative race‐specific OCT data that may enhance clinical glaucoma practice.

Acute Peripapillary Retinal Pigment Epithelium Changes Associated with Acute Intraocular Pressure Elevation

To assess changes in the peripapillary retinal pigment epithelium (RPE) in association with an acute intraocular pressure (IOP) elevation provoked by a dark room prone provocative test (DRPPT). Prospective, comparative clinical observational study. Nineteen study group eyes (14 individuals) and 26 control eyes (21 patients). Individuals with normal optic nerve heads (ONHs) underwent a DRPPT in a standardized manner. They were stratified into a study group with an IOP rise of more than 15 mmHg at the end of the DRPPT and a control group with an IOP rise between 2 and 4 mmHg. Before and at the end of the test, the ONH was imaged by spectral-domain optical coherence tomography (OCT). Morphologic features of the RPE at the peripapillary end of Bruch's membrane. After a mean IOP rise by 32.1±9.5 mmHg (range, 17-47 mmHg), 18 (95%) eyes in the study group showed a folding or a centrifugal sliding, or both, of the end of the RPE layer on the peripapillary Bruch's membrane. The RPE changes were located most often at the temporal pole of the ONH (16 eyes [89%]), followed by the nasal pole (2 eyes [11%]). The RPE changes were not detected at the inferior or superior disc poles. Some eyes with marked RPE changes showed corresponding changes in peripapillary β zone on infrared ONH photographs. In 7 eyes of 7 participants with OCT images obtained on the day after the PRPPT, the RPE end moved back to the end of peripapillary Bruch's membrane. The single eye of the study group without exhibiting IOP rise-associated RPE changes showed an interdigitation zone line indistinguishable from Bruch's membrane line on OCT images. None of the control eyes showed RPE changes. The difference in frequency of RPE changes between study and control groups was significant (P < 0.001). Eyes with an acute rise in IOP (>15 mmHg) showed a folding and centrifugal sliding of the peripapillary RPE and, after IOP reduction, centripetal RPE movement. These observations may be of interest to elucidate the pathogenesis of peripapillary atrophy in glaucoma.

Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head.

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.

Sectoral variations in the distribution of axonal cytoskeleton proteins in the human optic nerve head

Axonal cytoskeleton proteins are intrinsically related to retinal ganglion cell (RGC) health and disease. This study quantifies and documents the sectoral distribution of axonal cytoskeleton proteins in the different laminar compartments of the normal human optic nerve head (ONH). Nine human eyes were used (mean age of 46.9 ± 3.7 years). Coronal sections of the prelaminar, anterior lamina cribrosa, posterior lamina cribrosa and retrolaminar regions were examined using immunohistochemical and confocal microscopy techniques. The axonal cytoskeleton was studied using antibodies to neurofilament light (NFL), neurofilament medium (NFM), neurofilament heavy (NFH), phosphorylated NFH (NFHp), microtubule associated protein-1 (MAP-1) and tubulin. Axonal cytoskeleton intensity was quantified in a standardized manner and comparisons were made within and between laminar regions. The intensity of NFM, NFH and NFHp is significantly greater in the nasal and peripheral sectors of the prelaminar, anterior lamina cribrosa and posterior lamina cribrosa regions. There is no significant difference in the distribution of NFL, tubulin and MAP-1 proteins between sectors in any laminar region. The intensity of all axonal cytoskeleton proteins in unmyelinated laminar regions is greater than the retrolaminar region. The distribution of all cytoskeleton proteins in the myelinated, retrolaminar region of the optic nerve appears to be relatively even. The distribution of axonal cytoskeleton proteins may have relevance for understanding the vulnerability of distinct ONH sectors to intraocular pressure- and ischaemia-mediated damage. The findings in this study may be important for understanding patho-physiological mechanisms involved in glaucomatous and ischaemic optic neuropathy.

Ocular hypertension: general characteristics and estimated cerebrospinal fluid pressure. The Beijing Eye Study 2011.

PurposeTo examine characteristics of ocular hypertensive subjects and potential associations with estimated cerebrospinal fluid pressure (estCSFP).MethodsThe population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. Ocular hypertension was defined as intraocular pressure (IOP) >21 mmHg, normal optic nerve head appearance and normal retinal nerve fiber layer thickness. IOP was corrected for its dependence on central corneal thickness (CCT) and corneal curvature radius. Estimated CSFP was calculated as CSFP [mmHg] = 0.44×Body Mass Index [kg/m2]+0.16×Diastolic Blood Pressure [mmHg]−0.18×Age [Years]−1.91. Estimated trans-lamina cribrosa pressure difference (estTLCPD) was IOP–estCSFP.ResultsEstCSFP (10.5±3.6 mmHg versus 9.0±3.7 mmHg; P = 0.003) and estTLCPD (12.0±4.4 mmHg versus 5.4±3.8 mmHg; P<0.001) were higher in the ocular hypertensive group than in the normotensive group. In binary regression analysis, ocular hypertension was associated with increased estCSFP (P = 0.03; odds ratio (OR): 1.08; 95% confidence interval (CI): 1.01, 1.17) after adjusting for prevalence of arterial hypertension (P = 0.07; OR: 1.79; 95%CI: 0.96, 3.34), retinal nerve fiber layer thickness (P = 0.03; OR: 0.97; 95%CI: 0.95, 0.997) and blood glucose concentration (P = 0.006; OR: 1.17; 95%CI: 1.04, 1.30).ConclusionsOcular hypertensive subjects (with IOP correction for CCT and corneal curvature) as compared to ocular normotensive subjects had a significantly higher estCSFP in univariate analysis and in multivariate analysis. Despite of a higher estCSFP, estTLCPD was still markedly higher in ocular hypertensive eyes than in ocular normotensive eyes.

Spectral-domain optical coherence tomography evaluation of the cornea, retina, and optic nerve in normal horses.

To determine the feasibility of using a handheld spectral-domain optical coherence tomography (SD-OCT) instrument to characterize normal corneal, retinal, and optic nerve head anatomy in vivo in standing horses. Clinically normal horses under sedation, palpebral nerve blockage, and pharmacologically induced mydriasis were imaged with a SD-OCT instrument (Envisu SD-OCT, Bioptigen, Inc., Morrisville, NC). Radial volumes from the cornea (axial, superior, inferior, nasal, and temporal), and rectangular volumes from the retina (dorsal, ventral, nasal, and temporal) and optic nerve head were acquired. Manual measurements of the corneal layers within the five regions, retinal and nerve fiber layer thickness in the four different regions adjacent to the ONH, and vertical and horizontal axis of the optic nerve head (ONH) and optic cup (OC) were obtained using the same device. Total corneal thickness (mean ± SD) measurements were 800 ± 50, 937 ± 61, 956 ± 61, 912 ± 65, and 884 ± 68 μm for the axial, superior, inferior, nasal, and temporal regions, respectively. The highest total retinal and nerve fiber layer thickness (mean ± SD), at the level of the ONH, was found nasally 459 ± 115 and 377 ± 116 μm, respectively, followed by the temporal, dorsal, and ventral quadrants. The dimensions of the ONH and OC (mean ± SD) were 3.682 ± 0.276 and 2.175 ± 0.502 mm for the horizontal, and 3.012 ± 0.278 and 2.035 ± 0.488 mm for the vertical axis. The SD-OCT instrument employed in this study may be used on sedated horses and allows the acquisition of high-resolution images, and thickness measurements involving the cornea, retina, and optic nerve.

Retinal regeneration is facilitated by the presence of surviving neurons

Teleost fish regenerate their retinas after damage, in contrast to mammals. In zebrafish subjected to an extensive ouabain-induced lesion that destroys all neurons and spares Müller glia, functional recovery and restoration of normal optic nerve head (ONH) diameter take place at 100 days postinjury. Subsequently, regenerated retinas overproduce cells in the retinal ganglion cell (RGC) layer, and the ONH becomes enlarged. Here, we test the hypothesis that a selective injury, which spares photoreceptors and Müller glia, results in faster functional recovery and fewer long-term histological abnormalities. Following this selective retinal damage, recovery of visual function required 60 days, consistent with this hypothesis. In contrast to extensively damaged retinas, selectively damaged retinas showed fewer histological errors and did not overproduce neurons. Extensively damaged retinas had RGC axons that were delayed in pathfinding to the ONH, and showed misrouted axons within the ONH, suggesting that delayed functional recovery following an extensive lesion is related to defects in RGC axons exiting the eye and/or reaching their central targets. The atoh7, fgf8a, Sonic hedgehog (shha), and netrin-1 genes were differentially expressed, and the distribution of hedgehog protein was disrupted after extensive damage as compared with selective damage. Confirming a role for Shh signaling in supporting rapid regeneration, shha(t4) +/- zebrafish showed delayed functional recovery after selective damage. We suggest that surviving retinal neurons provide structural/molecular information to regenerating neurons, and that this patterning mechanism regulates factors such as Shh. These factors in turn control neuronal number, retinal lamination, and RGC axon pathfinding during retinal regeneration.

Distribution of αB-Crystallin in the Central Retina and Optic Nerve Head of Different Mammals and its Changes during Outer and Inner Retinal Degeneration

Purpose: To investigate species differences in the distribution and localization of alpha B-crystallin (ABC) in the normal retina and optic nerve head region, and to describe changes during outer and inner retina degeneration. Material and methods: Animals studied included mice, rats, cats, pigs, cows, and monkeys. Sections of the optic nerve and central retina were labeled with antibodies against ABC and glial fibrillary acidic protein (GFAP). Results: ABC was located in astrocytes and Muller cells with different intensities. During outer retina degeneration (dystrophic rat and Abyssinian cat), only late stages showed an increase in ABC in the retina and optic nerve head. Inner retina degeneration in the glaucoma mouse model showed no increase of ABC. In the monkey glaucoma model, only the innermost layer of the optic nerve head showed increased labeling for ABC. Conclusions: The distribution of ABC is species dependent and is (excluding the mouse) present in the nerve fiber layer of the retina and in the optic nerve head (localization of astrocytes). Chronic retinal degeneration does not necessarily lead to an over-expression of ABC. While in outer retinal degeneration induction was predominantly present in late stages, pressure-induced glaucoma led to a specific increase in ABC already in early stages indicating a local stress-response in this region.