A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation.

Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives-methylparaben and phenoxyethanol-but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.

Ocular Findings Associated with Hypoparathyroidism.

Purpose: To determine the corneal and retinal changes associated with serum calcium, phosphorus and parathyroid hormone (PTH) levels in patients with hypoparathyroidism.Methods: Patients who were under follow-up for hypoparathyroidism in the endocrinology department were included in the study. All participants underwent a complete ophthalmological examination. Moreover, central corneal thickness (CCT), anterior chamber depth (ACD), retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness were recorded. Serum biochemical parameters were recorded.Results: In a total of 75 patients (35 in the hypoparathyroidism group and 40 in the healthy control group) were included in this study. Central corneal thickness (519.95 ± 33.21 vs. 539.10 ± 32.96, p: 0.001) and RNFL (105.10 ± 11.89 vs. 113.56 ± 9.54, p: 0.005) were significantly thinner and ACD was significantly deeper in the hypoparathyroidism group.Conclusion: We determined thinner CCT and RNFL values in patients with hypoparathyroidism related to serum calcium levels together with a significant deepness in ACD.

Determinants of lamina cribrosa depth in healthy Asian eyes: the Singapore Epidemiology Eye Study.

AIM: To investigate the determinants of lamina cribrosa depth (LCD) in healthy eyes of Chinese and Indian Singaporean adults. METHODS: The optic nerve head (ONH) of the right eye of 1396 subjects (628 Chinese and 768 Indian subjects) was imaged with optical coherence tomography (OCT, Spectralis, Heidelberg, Germany). LCD was defined as the distance from the Bruch's membrane opening (LCD-BMO) or the peripapillary sclera (LCD-PPS) reference plane to the laminar surface. A linear regression model was used to evaluate the relationship between the LCD and its determinants. RESULTS: Both LCDs were significantly different between the two races (LCD-BMO: 421.95 (95% CI 365.32 to 491.79) µm in Chinese vs 430.39 (367.46-509.81) µm in Indians, p=0.021; and LCD-PPS: 353.34 (300.98-421.45) µm in Chinese vs 376.76 (313.39-459.78) µm in Indians, p<0.001). In the multivariable regression analysis, the LCD-PPS of the whole cohort was independently associated with females (ß=-31.93, p<0.001), Indians subjects (ß=21.39, p=0.004) (Chinese as the reference), axial length (Axl) (ß=-6.68, p=0.032), retinal nerve fibre layer thickness (RNFL) (ß=0.71, p=0.019), choroidal thickness (ChT) (ß=0.41, p<0.001), vertical cup disc ratio (VCDR) (ß=24.42, p<0.001) and disc size (ß=-60.75, p=0.001). For every 1 year older in age, the LCD-PPS was deeper on average by 1.95 µm in Chinese subjects (p=0.01) but there was no association in Indians subjects (p=0.851). CONCLUSIONS: The LCD was influenced by age, gender, race, Axl, RNFL, ChT, VCDR and disc size. This normative LCD database may facilitate a more accurate assessment of ONH cupping using OCT in Asian populations.

Neuroprotective effects of Acer palmatum thumb. leaf extract (KIOM-2015E) against ischemia/reperfusion-induced injury in the rat retina.

Purpose: The present study aimed to determine whether the administration of Acer palmatum thumb. leaf extract (KIOM-2015E) protects against the degeneration of rat retinal ganglion cells after ischemia/reperfusion (I/R) induced by midbrain cerebral artery occlusion (MCAO). Methods: Sprague-Dawley rats were subjected to 90 min of MCAO, which produces transient ischemia in both the retina and brain due to the use of an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. This was followed by reperfusion under anesthesia with isoflurane. The day after surgery, the eyes were treated three times (eye drop) or one time (oral administration) daily with KIOM-2015E for five days. Retinal histology was assessed in flat mounts and vertical sections to determine the effect of KIOM-2015E on I/R injury. Results: A significant loss of brain-specific homeobox/POU domain protein 3A (Brn3a) and neuron-specific class III beta-tubulin (Tuj-1) fluorescence and a marked increase in glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) expression were observed after five days in the PBS-treated MCAO group compared to the sham-operated control group. However, KIOM-2015E treatment reduced (1) MCAO-induced upregulation of GFAP and GS, (2) retinal ganglion cell loss, (3) nerve fiber degeneration, and (4) the number of TUNEL-positive cells. KIOM-2015E application also increased staining for parvalbumin (a marker of horizontal cell associated calcium-binding protein and amacrine cells) and recoverin (a marker of photoreceptor expression) in rats subjected to MCAO-induced retinal damage. Conclusions: Our findings indicated that KIOM-2015E treatment exerted protective effects against retinal damage following MCAO injury and that this extract may aid in the development of novel therapeutic strategies for retinal diseases, such as glaucoma and age-related macular disease.

Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Temporal Raphe Sign in Elderly Patients With Large Optic Disc Cupping: Its Evaluation as a Predictive Factor for Glaucoma Conversion.

PURPOSE: To determine baseline clinical features associated with conversion to glaucoma in elderly patients with large optic-disc cupping. DESIGN: Retrospective cohort study. METHODS: Seventy-two eyes of 72 untreated elderly (≥65-year-old) patients with large vertical cup-to-disc ratio (CDR ≥0.7) and without any other glaucomatous findings were included. They had undergone a full ophthalmologic examination twice per year for at least 5 years. The optic nerve head (ONH), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell-inner plexiform layer (GCIPL) were imaged with Cirrus high-definition optical coherence tomography (OCT). Presence of temporal raphe sign on the OCT's GCIPL thickness map was assessed as one of the morphologic factors. Conversion to normal-tension glaucoma (NTG) was defined as structural or functional deterioration on either red-free RNFL photography or standard automated perimetry, respectively. The utility of the baseline factors associated with conversion to NTG were identified. RESULTS: During the 5.5-year follow-up, 19 eyes (26.4%) converted to NTG. There were no significant differences in demographics, systemic factors, intraocular pressure factors, or OCT parameters between the nonconverters and converters. Interestingly, the temporal raphe sign was observed in the converters (18/19, 94.7%) much more frequently than in the nonconverters (3/53, 5.7%, P < .001) at baseline. A Cox proportional hazards model indicated the significant influences of temporal raphe sign positivity (hazard ratio 6.823, 95% confidence interval 2.574, 18.088, P < .001) on conversion to NTG. CONCLUSIONS: In elderly subjects with large CDR, temporal raphe sign positivity on the baseline macular GCIPL thickness map was associated with faster conversion to NTG.

Effect of Trabeculectomy on OCT Measurements of the Optic Nerve Head Neuroretinal Rim Tissue.

Purpose: Ophthalmologists commonly perform glaucoma surgery to treat progressive glaucoma. Few studies have examined the stability of OCT neuroretinal rim parameters after glaucoma surgery for ongoing detection of glaucoma progression. Design: Longitudinal cohort study. Participants: 20 eyes (16 subjects) with primary open angle glaucoma who had undergone a trabeculectomy. Methods: We calculated the change in OCT parameters (minimum rim area (MRA), minimum rim width (MRW), Bruch's membrane opening (BMO) area, mean cup depth (MCD), anterior lamina cribrosa surface depth (ALCSD), prelaminar tissue thickness (PLTT), retinal nerve fiber layer thickness (RFNLT) during an interval from the visit before the surgery to the visit after the surgery, a span of approximately 6-months. We also calculated changes in the same eyes over two separate 6-month intervals that did not contain trabeculectomy to serve as control. We compared these intervals using a generalized linear model (with compound symmetry correlation structure), accounting for the correlation between time intervals for the same eye. Main outcomes measures: MRW, MRA, angle above the reference plane for MRW and MRA, BMO area, MCD, mean ALCSD, PLTT, RNFLT and visual field parameters (mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI)). Results: The intervals containing trabeculectomy showed a significant decrease in intraocular pressure (-9.2 mmHg, p<.001) when compared to control intervals. Likewise, the following neuroretinal rim parameters showed significant changes with trabeculectomy: increased MRW (+6.04µm, p=.001), increased MRA (+0.014mm2, p=.024), increased angle above reference plane of MRW (+2.64°, p<.001), decreased MCD (-11.6µm, p=.007), and decreased mean ALCSD (-18.91µm, p=.006). This is consistent with an increase in rim tissue thickness and a more anterior position of the ILM and ALCS relative to the BMO plane. Conversely, RNFLT change was not significantly different between trabeculectomy and control intervals (p=.37). Conclusion: Trabeculectomy resulted in anatomical changes to the ONH rim associated with reduced glaucomatous cupping. The RNFL thickness may be a more stable measure of disease progression that clinicians can use to monitor across time intervals containing glaucoma surgery.

Bruch's Membrane Opening Minimum Rim Width Provides Objective Differentiation between Glaucoma and Nonglaucomatous Optic Neuropathies.

PURPOSE: A challenging clinical scenario is distinguishing between normal tension glaucoma (NTG) and non-glaucomatous optic neuropathies (NGON). The key to the assessment remains identifying the presence of optic nerve head cupping. Recent optical coherence tomography (OCT) measurements now allow objective assessment of cupping by minimum rim width at Bruch's membrane opening (MRW-BMO). This study assessed the hypothesis that the MRW-BMO measurement quantifies cupping and therefore can differentiate between NTG and NGON. DESIGN: Diagnostic evaluation with area under the curve. METHODS: Setting: multicenter tertiary hospitals and outpatient clinics. PATIENT POPULATION: 81 eyes of 81 patients were enrolled, 27 with NTG and 54 with NGON, including ischemic optic neuropathy, previous optic neuritis, and compressive and inherited optic neuropathies. All NGON patients with intraocular pressure >21 mm Hg, narrow drainage angles, or a family history of glaucoma were excluded. Observational procedure: optic disc OCT images were obtained of both the retinal nerve fiber layer thickness and the MRW-BMO. MAIN OUTCOME MEASUREMENTS: the utility of the MRW-BMO in differentiating GON from NGON was assessed using the area under the curve (AUC) estimated from a logistic regression model. RESULTS: The 5-fold cross-validated AUC for glaucoma versus nonglaucoma from logistic regression models using MRW-BMO values from all sectors was 0.95 (95% confidence interval: 0.86-1.00). CONCLUSIONS: The measurement of MRW-BMO effectively differentiates between NTG and NGON with a high level of sensitivity and specificity. Incorporating this measurement into routine glaucoma assessment may provide a robust method of assisting clinicians to improve diagnosis and therefore treatment of optic nerve diseases.

The Relationship Between Optic Nerve Cup-to-Disc Ratio and Retinal Nerve Fiber Layer Thickness in Suspected Pediatric Glaucoma.

PURPOSE: To evaluate the relationship between optic nerve cup-to-disc ratio and peripapillary retinal nerve fiber layer (RNFL) thickness in suspected pediatric glaucoma with large cup-to-disc ratios. METHODS: This was a retrospective study undertaken at a single academic institution. Eighty-six eyes of 43 patients who presented with large (≥ 0.5) cup-to-disc ratios in both eyes and without elevated intraocular pressure were evaluated using spectral-domain optical coherence tomography. Global and sectoral peripapillary RNFL thickness measurements, Bruch's membrane opening size, refractive error in spherical equivalents, and intraocular pressure levels were recorded for all patients. Cup-to-disc ratios were manually derived using digital fundus images (D-cup-to-disc ratio). Parameters were compared between gender or race by t tests or analysis of variance. The differences in the relationship among the clinical parameters between two eyes were assessed using generalized estimation equation modeling followed by Pearson's correlation analysis. RESULTS: Forty-three patients (25 boys and 18 girls) with a mean age of 9.3 ± 2.7 years (range: 5 to 15 years) were included. The mean global peripapillary RNFL thickness and the D-cup-to-disc ratio of study eyes were 99.0 ± 9.2 µm and 0.66 ± 0.03, respectively. The peripapillary RNFL thickness was found to be correlated with refractive error (r = 0.404; P = .008) and Bruch's membrane opening size (r = 0.410; P = .008) but not with cup-to-disc ratios (r = 0.029; P = .858) or patient age (r = -0.044; P = .797). CONCLUSIONS: In patients with suspected pediatric glaucoma who present with large cup-to-disc ratios, RNFL thickness does not correlate with the degree of optic nerve cupping. Myopic refractive errors and Bruch's membrane opening size need to be taken into consideration to prevent misinterpretation of peripapillary RNFL measurements. [J Pediatr Ophthalmol Strabismus. 2020;57(2):90-96.].

Dynamics of structural reversal in Bruch's membrane opening-based morphometrics after glaucoma drainage device surgery.

PURPOSE: Structural reversal of disc cupping is a known phenomenon after trabeculectomy. The aim of this retrospective, longitudinal, cross-sectional analysis was to evaluate the postoperative dynamics of Bruch's membrane opening-based morphometrics of the optic nerve head following glaucoma drainage device surgery. METHODS: Forty-three eyes, treated by glaucoma drainage device surgery, were included in the study. Individual changes in the spectral domain optic coherence tomography (SD-OCT) parameters Bruch's membrane opening minimum rim width (BMO-MRW), Bruch's membrane opening minimum rim area (BMO-MRA) and peripapillary retinal nerve fiber layer (RNFL) thickness as well as mean defect in 30-2 perimetry were analyzed. Changes were correlated to postoperative intraocular pressure levels over time. Available follow-up visits were aggregated and grouped into a short-term follow-up (20 to 180 days after surgery), a midterm follow-up (181 to 360 days after surgery) and a long-term follow-up (more than 360 days after surgery). RESULTS: In short-term follow-up, BMO-MRW and BMO-MRA increased significantly (p <= 0.034). This increase correlated negatively with the intraocular pressure at the time of the follow-up (Pearson's rho = - 0.49; p = 0.039). From 6 months after surgery on, there was no statistically significant change in BMO-MRW and BMO-MRA (p >= 0.207). RNFL thickness and mean defect of 30-2 perimetry showed no significant changes after GDD implantation (p >= 0.189). CONCLUSIONS: Lowering of intraocular pressure by glaucoma drainage device surgery leads to an increase of Bruch's membrane opening based parameters in the first 6 months after surgery. These changes have to be taken into account when evaluating patients' longitudinal follow-up after glaucoma drainage device implantation.

Quantitative analysis of radial peripapillary capillary plexuses in patients with clinically unilateral pseudoexfoliation syndrome.

PURPOSE: The aim of this study was to image the radial peripapillary capillary vessel densities (RPCvds) of the affected eyes and fellow unaffected eyes of individuals with unilateral pseudoexfoliation syndrome (PES) using optical coherence tomography angiography (OCTA) and to compare the RPCvds with those of normal age-matched individuals. METHODS: The eyes were divided into three groups: the pseudoexfoliative material (PXM)-positive eyes of patients with clinically unilateral PES (study eyes), the fellow eyes of the PXM-positive patients (fellow eyes), and the eyes of healthy patients (control eyes). Those patients with glaucomatous findings, including peripapillary hemorrhaging, cupping, notching, focal thinning of the neuroretinal rim, or intraocular pressure readings greater than 21 mmHg, were excluded from the study. The RPCvd (%), peripapillary retinal nerve fiber layer (RNFL) thickness (µm), cup/disc area ratio, rim area (mm2), disc area (mm2), and cup volume (mm3) were automatically calculated via OCTA. RESULTS: This cross-sectional comparative prospective study included 128 eyes of 88 patients: 40 PXM-positive eyes, 40 fellow eyes, and 48 control eyes. The RPCvds and RNFL thicknesses in the peripapillary region were significantly lower in the study eyes than in the fellow eyes and the control eyes (p = 0.011 and p = 0.011, p = 0.009 and p = 0.004, respectively). There were no significant differences between the fellow eyes and the control eyes with regard to the RPCvd and RNFL values in any region (p > 0.05 for all). CONCLUSION: Lower RPCvds could provoke capillary deficiency and deterioration of the perfusion of the optic nerve head in patients with PES.

Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study.

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

A neuroglia-based interpretation of glaucomatous neuroretinal rim thinning in the optic nerve head.

Neuroretinal rim thinning (NRR) is a characteristic glaucomatous optic disc change. However, the precise mechanism of the rim thinning has not been completely elucidated. This review focuses on the structural role of the glioarchitecture in the formation of the glaucomatous NRR thinning. The NRR is a glia-framed structure, with honeycomb geometry and mechanically reinforced astrocyte processes along the transverse plane. When neural damage selectively involves the neuron and spares the glia, the gross structure of the tissue is preserved. The disorganization and loss of the glioarchitecture are the two hallmarks of optic nerve head (ONH) remodeling in glaucoma that leads to the thinning of NRR tissue upon axonal loss. This is in contrast to most non-glaucomatous optic neuropathies with optic disc pallor where hypertrophy of the glioarchitecture is associated with the seemingly absent optic disc cupping. Arteritic anterior ischemic optic neuropathy is an exception where pan-necrosis of ONH tissue leads to NRR thinning. Milder ischemia indicates selective neuronal loss that spares glia in non-arteritic anterior ischemic optic neuropathy. The biological reason is the heterogeneous glial response determined by the site, type, and severity of the injury. The neuroglial interpretation explains how the cellular changes underlie the clinical findings. Updated understandings on glial responses illustrate the mechanical, microenvironmental, and microglial modulation of activated astrocytes in glaucoma. Findings relevant to the possible mechanism of the astrocyte death in advanced glaucoma are also emerging. Ultimately, a better understanding of glaucomatous glial response may lead to glia-targeting neuroprotection in the future.

Single-session cortical electrical stimulation enhances the efficacy of rehabilitative motor training after spinal cord injury in rats.

Low neuronal cAMP levels in adults and a further decline following traumatic central nervous system (CNS) injury has been associated with the limited ability of neurons to regenerate. An approach to increase neuronal cAMP levels post injury is electrical stimulation. Stimulation as a tool to promote neuronal growth has largely been studied in the peripheral nervous system or in spared fibers of the CNS and this research suggests that a single session of electrical stimulation is sufficient to initiate a long-lasting axonal growth program. Here, we sought to promote plasticity and growth of the injured corticospinal tract with electrical cortical stimulation immediately after its spinal injury. Moreover, given the importance of rehabilitative motor training in the clinical setting and in translating plasticity into functional recovery, we applied training as a standard treatment to all rats (i.e., with or without electrical stimulation). Our findings show that electrical cortical stimulation did improve recovery in forelimb function compared to the recovery in unstimulated animals. This recovery is likely linked to increased corticospinal tract plasticity as evidenced by a significant increase in sprouting of collaterals above the lesion site, but not to increased regenerative growth through the lesion itself.

Posttreatment Intervention With Lycium Barbarum Polysaccharides is Neuroprotective in a Rat Model of Chronic Ocular Hypertension.

Purpose: To investigate the neuroprotective effects of Lycium barbarum polysaccharides (LBP) against chronic ocular hypertension (OHT) in rats and to consider if effects differed when treatment was applied before (pretreatment) or during (posttreatment) chronic IOP elevation. Methods: Sprague-Dawley rats (10-weeks old) underwent suture implantation around the limbus for 15 weeks (OHT) or 1 day (sham). Four experimental groups were studied, three OHT groups (n = 8 each) treated either with vehicle (PBS), LBP pretreatment or posttreatment, and a sham control (n = 5) received no treatment. LBP (1 mg/kg) pre- and posttreatment were commenced at 1 week before and 4 weeks after OHT induction, respectively. Treatments continued up through week 15. IOP was monitored twice weekly for 15 weeks. Optical coherence tomography and ERG were measured at baseline, week 4, 8, 12, and 15. Eyes were collected for ganglion cell layer (GCL) histologic analysis at week 15. Results: Suture implantation successfully induced approximately 50% IOP elevation and the cumulative IOP was similar between the three OHT groups. When compared with vehicle control (week 4: -23 ± 5%, P = 0.03), LBP pretreatment delayed the onset of retinal nerve fiber layer (RNFL) thinning (week 4, 8: -2 ± 7%, -11 ± 3%, P > 0.05) and arrested further reduction up through week 15 (-10 ± 4%, P > 0.05). LBP posttreatment intervention showed no significant change in rate of loss (week 4, 15: -25 ± 4.1%, -28 ± 3%). However, both LBP treatments preserved the retinal ganglion cells (RGC) and retinal functions up to week 15, which were significantly reduced in vehicle control. Conclusions: LBP posttreatment arrested the subsequent neuronal degeneration after treatment commencement and preserved RGC density and retinal functions in a chronic OHT model, which was comparable with pretreatment outcomes.

Longitudinal reproducibility of spectral domain optical coherence tomography in children with physiologic cupping and stable glaucoma.

PURPOSE: To determine whether Spectralis (Heidelberg, Germany) spectral domain optical coherence tomography (SD-OCT) measurements are reproducible over time in children with physiologic cupping and stable glaucoma. METHODS: Subjects were identified from a subset of participants in an earlier retrospective study conducted by our group and included children (<18 years of age) with physiologic cupping and stable primary congenital glaucoma (PCG) having had at least 2 SD-OCTs over a period of more than 1 between April 2010 and September 2015. Thicknesses of average peripapillary retinal nerve fiber layer (pRNFL) and six individual sectors and volumes of three segmented retinal layers and total retina were measured. Spectralis review software was used for segmentation. Intraclass correlation coefficients (ICC) and coefficient of variation (COV) were calculated. RESULTS: A total of 35 eyes of 35 children were included: 15 eyes had physiologic cupping; 20 eyes, PCG. Mean ages at initial SD-OCT were 11.2 ± 3.3 years and 9.7 ± 3.3, respectively; mean intervals between first and last imaging were 2.2 ± 1.1 and 3.0 ± 1.4 years, respectively. ICCs across three visits for both groups for average and sectoral pRNFL thicknesses were 0.887-0.997 and for segmented retinal volumes were 0.806-0.993. ICCs for total retinal volume for physiologic cupping and PCG were 0.993 and 0.954, respectively. COVs for average pRNFL thickness were 0.9% and 1.7%, respectively. For all other measurements, COVs ranged from 0.3% to 5.4%. CONCLUSIONS: Reproducibility of longitudinal SD-OCT measurements for average pRNFL thickness in children with stable glaucoma over about 2 years is comparable to short-term reproducibility (COV) in normal children (1.16%) and normal and glaucoma adults (1.62%-3.4%).

ß-alanine supplementation induces taurine depletion and causes alterations of the retinal nerve fiber layer and axonal transport by retinal ganglion cells.

To study the effect of taurine depletion induced by ß-alanine supplementation in the retinal nerve fiber layer (RNFL), and retinal ganglion cell (RGC) survival and axonal transport. Albino Sprague-Dawley rats were divided into two groups: one group received ß-alanine supplementation (3%) in the drinking water during 2 months to induce taurine depletion, and the other group received regular water. After one month, half of the rats from each group were exposed to light. Retinas were analyzed in-vivo using Spectral-Domain Optical Coherence Tomography (SD-OCT). Prior to processing, RGCs were retrogradely traced with fluorogold (FG) applied to both superior colliculi, to assess the state of their retrograde axonal transport. Retinas were dissected as wholemounts, surviving RGCs were immunoidentified with Brn3a, and the RNFL with phosphorylated high-molecular-weight subunit of the neurofilament triplet (pNFH) antibodies. ß-alanine supplementation decreases significantly taurine plasma levels and causes a significant reduction of the RNFL thickness that is increased after light exposure. An abnormal pNFH immunoreactivity in some RGC bodies, their proximal dendrites and axons, and a further diminution of the mean number of FG-traced RGCs compared with Brn3a+RGCs, indicate that their retrograde axonal transport is affected. In conclusion, taurine depletion causes RGC loss and axonal transport impairment. Finally, our results suggest that care should be taken when ingesting ß-alanine supplements due to the limited understanding of their potential adverse effects.

Clinical, ultrasonographic and optical coherence tomography correlation of optic nerve head cupping in glaucoma patients.

Purpose: To ascertain if ultrasound (USG) B-scan examination of the optic nerve head (ONH) can be a useful tool to diagnose and quantify glaucomatous cupping. Methods: A cross-sectional observational study of 48 eyes of 48 patients with clear ocular media and cup-disc ratio of (CDR) ≥0.6 were included. The disc was studied by + 90D examination, USG B-scan and ONH Optical coherence tomography (OCT) by three masked observers. Observer-1 assessed the clinical CDR, observer-2recordedopticcup diameter on USG B-scan and observer-3performed ONH OCT to note the software computed average CDR. Measurements of cupping obtained by these 3 methods were compared and their relative strengths determined. The interdependency between variables was further studied using regression analysis. Results: Clinically assessed disc ratios of 0.6, 0.7, 0.8, 0.9, and total corresponded to USG cup measures of 1.02 ± 0.11 mm, 1.23 ± 0.14 mm, 1.35 ± 0.072 mm, 1.45 ± 0.084 mm, 1.75 ± 0.15 mm and OCT average CDR of 0.62 ± 0.087, 0.68 ± 0.060, 0.75 ± 0.078, 0.81 ± 0.036, 0.89 ± 0.038, respectively. There was an excellent correlation between the three arms, with Pearson's co-efficient (r) of 0.87, P < 0.001 between clinical and USG cupping; r = 0.89, P < 0.001 between clinical and OCT cupping; and r = 0.88, P < 0.001 between USG and OCT cupping. A relation of y = 1.64x + 0.03 was obtained between them, where y stands for USG cup diameter and x stands for the observed clinical CDR. Conclusion: Ultrasonographic measurement of optic cup diameter corresponds well to clinical ONH cupping. Therefore, it can reliably be used in quantifying ONH cupping in cases of media opacities which preclude optic disc visualization.

Disc Configuration as a Risk and Prognostic Factor in NAION: The Impact of Cup to Disc Ratio, Disc Diameter, and Crowding Index.

Purpose: The presence of the so called disc at risk (a small disc with no cupping) has been considered the main risk factor for the development of non-arteritic anterior ischemic optic neuropathy (NAION). However its role as a prognostic factor has not been studied. Our aim was to determine the weight of disc configuration as a risk and a prognostic factor for NAION. Methods: Case control study. Forty eyes of 40 patients who were diagnosed with NAION between 2008 and 2017, and 120 controls (3 controls for each patient) were included in the study. Disc diameter (DD), cup to disc ratio (CDR), and peripapillar retinal nerve fiber layer thickness (RNFLT) of the non-affected eye were measured using optic coherence tomography (3D OCT 2000, Topcon). Crowding index (CI) was defined as the quotient of average RNFLT and disc area. Mean deviation (MD) at the time of diagnosis and at least three months later was determined using a Humphrey Visual Field Analyzer (SITA standard 24-2 strategy). Visual acuity (VA) was measured using Snellen charts and transformed into LogMAR values. Results: Only CDR was found to be a risk factor for NAION. No correlationship was found between CI and visual loss. Conclusions: DD and CI did not show value as either prognostic or risk factors. Glial tissue may be a part of the content of the optic disc as important as axons. Our results are in line with the latest studies about NAION pathophysiology. Contrary to classic thinking, these papers have not found smaller disc diameters, but smaller values of lamina cribosa depth in NAION patients.