The Robust Lamina Cribrosa Vasculature: Perfusion and Oxygenation Under Elevated Intraocular Pressure.

Purpose: Elevated intraocular pressure (IOP) is thought to cause lamina cribrosa (LC) blood vessel distortions and potentially collapse, adversely affecting LC hemodynamics, reducing oxygenation, and triggering, or contributing to, glaucomatous neuropathy. We assessed the robustness of LC perfusion and oxygenation to vessel collapses. Methods: From histology, we reconstructed three-dimensional eye-specific LC vessel networks of two healthy monkey eyes. We used numerical simulations to estimate LC perfusion and from this the oxygenation. We then evaluated the effects of collapsing a fraction of LC vessels (0%-36%). The collapsed vessels were selected through three scenarios: stochastic (collapse randomly), systematic (collapse strictly by the magnitude of local experimentally determined IOP-induced compression), and mixed (a combination of stochastic and systematic). Results: LC blood flow decreased linearly as vessels collapsed-faster for stochastic and mixed scenarios and slower for the systematic one. LC regions suffering severe hypoxia (oxygen <8 mm Hg) increased proportionally to the collapsed vessels in the systematic scenario. For the stochastic and mixed scenarios, severe hypoxia did not occur until 15% of vessels collapsed. Some LC regions had higher perfusion and oxygenation as vessels collapsed elsewhere. Some severely hypoxic regions maintained normal blood flow. Results were equivalent for both networks and patterns of experimental IOP-induced compression. Conclusions: LC blood flow was sensitive to distributed vessel collapses (stochastic and mixed) and moderately vulnerable to clustered collapses (systematic). Conversely, LC oxygenation was robust to distributed vessel collapses and sensitive to clustered collapses. Locally normal flow does not imply adequate oxygenation. The actual nature of IOP-induced vessel collapse remains unknown.

Can optic disc vessel density help in cases of residual disc elevation after shunt surgery in cases of idiopathic intracranial hypertension?

AIM: To detect if we can use the reduction in the optic disc vessel density as an indicator to the reduction in intracranial tension in patients with residual optic disc elevation after shunt surgery as fundus examination in those cases is not conclusive. PATIENTS AND METHOD: 21 patients with papilledema due to idiopathic intracranial hypertension underwent shunt surgery. Full neurological and ophthalmological assessments were done. The optic disc vessel density was measured before and 3 months after surgery. Patients were then divided according to the resolution of papilledema into 2 groups: 1) Residual disc elevation group. 2) Completely resolved disc edema group. CSF pressure was measured via lumber puncture preoperative for all patients and 3 months post-operative only for patients with residual disc edema. A comparison between both groups was done. RESULTS: There was a highly statistically significant difference between the two groups as regard the papilledema grade (the residual disc elevation group had a higher grade of papilledema) with P-value=0.000. As regard the difference in the preoperative optic disc vessel density between the two groups, there were statistically significant differences (optic disc vessel density was more in the residual disc elevation group). As regard the postoperative optic disc vessel density, there were non-significant differences between the two groups in whole image, inside disc and peripapillary vessel density (either in macro or microvasculature). CONCLUSION: The optic disc vessel density decreased with normal postoperative CSF opening pressure in cases with residual disc elevation postoperatively. Thus, in cases of residual optic disc swelling after shunt surgery, we can detect the reduction of intracranial pressure by the reduction in the optic disc vessel density which is a safe non-invasive technique. That may help in cases of residual disc elevation.

Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Biomechanical Correlations Between the Cornea and the Optic Nerve Head.

Purpose: A thin cornea is a potent risk factor for glaucoma. The underlying mechanisms remain unexplained. It has been postulated that central corneal thickness (CCT) may be a surrogate for biomechanical parameters of the posterior eye. In this study, we aimed to explore correlations of biomechanical responses between the cornea and the optic nerve head (ONH) and the peripapillary sclera (PPS) to elevated intraocular pressure (IOP), the primary risk factor of glaucoma. Methods: Inflation tests were performed in nine pairs of human donor globes. One eye of each pair was randomly assigned for cornea or posterior eye inflation. IOP was raised from 5 to 30 millimeters of mercury (mmHg) at 0.5 mmHg steps in the whole globe and the cornea or the ONH/PPS was imaged using a 50 MHz ultrasound probe. Correlation-based ultrasound speckle tracking was used to calculate tissue displacements and strains. Associations of radial, tangential, and shear strains at 30 mmHg between the cornea and the ONH or PPS were evaluated. Results: Corneal shear strain was significantly correlated with ONH shear strain (R = 0.857, P = 0.003) and PPS shear strain (R = 0.724, P = 0.028). CCT was not correlated with any strains in the cornea, ONH, or PPS. Conclusions: Our results suggested that an eye that experiences a larger shear strain in the cornea would likely experience a larger shear strain in its ONH and PPS at IOP elevations. The strong correlation between the cornea's and the ONH's shear response to IOP provides new insights and suggests a plausible explanation of the cornea's connection to glaucoma risk.

Evaluation of optical coherence tomography findings in patients with multiple sclerosis and glaucoma.

PURPOSE: Glaucoma and multiple sclerosis (MS) can cause optic disc pathology and, in this way, affect optical coherence tomography (OCT) data. In this context, the objective of this study is to investigate the changes in the mean, quadrant, and sector data measured by OCT in glaucoma and MS patients. METHODS: The sample of this prospective cohort study consisted of 42 MS patients (84 eyes), 34 Primary open-angle glaucomas patients (67 eyes), and 24 healthy control subjects (48 eyes). The MS group was divided into two groups according to the presence of a history of optic neuritis. Accordingly, those with a history of optic neuritis were included in the MS ON group, and those without a history of optic neuritis were included in the MS NON group. The differences between these groups in the mean, quadrant, and sector data related to the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were evaluated. RESULTS: Superior nasal (SN), superior temporal (ST), inferior nasal (IN), and superior quadrant (SUP) values were significantly lower in the glaucoma group than in the MS group (p < 0.05). The mean superior GCC (GCC SUP) value was significantly lower in the MS ON group than in the glaucoma group (p < 0.05). On the other hand, SN, ST, inferior temporal (IT), IN, average RNFL (AVE RNFL), semi-average superior RNFL (SUP AVE RNFL), semi-average inferior RNFL (INF AVE RNFL), SUP, and inferior quadrant RNFL (INF) values were significantly lower in the glaucoma group than in the MS NON group (p < 0.05). CONCLUSION: RNFL and GCC parameters get thinner in MS and glaucoma patients. While the inferior and superior RNFL quadrants are more frequently affected in glaucoma patients, the affected quadrants vary according to the presence of a history of optic neuritis in MS patients. It is noteworthy that the GCC superior quadrant was thin in MS ON patients. The findings of this study indicate that OCT data may be valuable in the differential diagnosis of glaucoma and MS.

[Preliminary clinical observation and analysis of structural changes of optic nerve head in glaucoma patients after visual training].

Objective: To investigate the effect of virtual reality visual training on remodeling optic nerve structures of glaucoma patients and analyze the influencing factors of visual training effect. Methods: A prospective non-randomized controlled trial was conducted. Glaucoma patients who presented to the Department of Ophthalmology, Beijing Shijitan Hospital between October 2021 and October 2022 were collected and divided into the training group or the control group according to their intentions. The training group accepted 3 months of visual training, while the control group did not. Optical coherence tomography was used to examine the disc edge area, cup volume, disc area, cup-to-disc ratio, and other parameters of the optic disc of both eyes of the patients at enrollment and after 3 months, and the changes of each parameter in the two groups were analyzed. Multivariate analysis was performed in the training group to investigate the effects of sex, age, visual field index, and mean defect on visual disc structure changes during visual training. Results: A total of 53 glaucoma patients (101 eyes) were included in the final analysis, among which the training group consisted of 27 cases (51 eyes), with 19 males and 8 females, and the age range was 48.0 (40.0, 61.0) years old. The control group comprised 26 cases (50 eyes), with 26 males and 11 females, and the age range was 54.0 (38.0, 63.0) years old. Compared with the control group, the deviation of cup volume was -0.006(-0.050, 0.015)mm3 (P<0.05), and the deviation of disc edge area was 0.00(-0.04, 0.05)mm2 (P<0. 05)in the visual training group after 3 months of visual training. The gender (OR=4.217, 95%CI=1.188-14.966) may be the influence factor of rim area. While,the mean defect (OR=1.526, 95%CI=0.245-9.491) was not that influential on rim area change. Conclusions: Visual training can increase the disc area and decrease the optic cup volume of the optic nerve in glaucoma patients. The rim area may be increased more easily after visual training in male glaucoma patients.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

Racial Differences in Diagnostic Accuracy of Retinal Nerve Fiber Layer Thickness in Primary Open-Angle Glaucoma.

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC: 0.86 and 0.90 in AD and ED, respectively, P =0.33). Adjustments for age, central corneal thickness, axial length, disc area, visual field mean deviation, and intraocular pressure yielded similar results. Conclusions: OCT-RNFLT has lower diagnostic accuracy in eyes of AD compared to those of ED. This finding was generally robust across two OCT instruments and remained after adjustment for many potential confounders. Further studies are needed to explore the potential sources of this difference.

Imagen en retromodo para el diagnóstico de drusas del disco óptico: una serie de casos / Retro-mode imaging for the diagnosis of optic disc drusen: A case series

Objetivo: Nuestro principal objetivo es el de comparar la capacidad para detectar las drusas del disco óptico (DDO) utilizando diversas técnicas de imágenes no-invasivas, incluida la novedosa técnica de imagen de retromodo (RMI). Como segundo objetivo analizamos las características morfológicas de las DDO bajo esta última técnica. Materiales y métodos: Este estudio incluyó un total de 7 pacientes con DDO bilaterales, obteniendo un total de 14 ojos analizados. Se utilizaron técnicas no invasivas de imágenes multimodales, que incluyeron fotografía multicolor del fondo de ojo (MC), reflectancia en infrarrojo (NIR), autofluorescencia en luz verde y en luz azul (G-FAF y B-FAF, respectivamente) y RMI. La FAF se utilizó como el método principal para el diagnóstico de DDO. Dos observadores realizaron las comparaciones, obteniendo las tasas de detección de cada uno de los métodos. Las mediciones cuantitativas de las DDO incluyeron el número, el perímetro (P) y el área (A) de las DDO identificadas mediante la técnica de RMI. Resultado: La edad promedio de los pacientes incluidos fue de 49,28±23,16 años; 5 de los 7 pacientes fueron de sexo masculino. La técnica de RMI pudo detectar DDO en todos los casos, con una sensibilidad del 100%, en comparación con MC (sensibilidad del 60,71%), NIR (sensibilidad del 60,71%), B-FAF (sensibilidad del 100%), G-FAF (sensibilidad del 100%). RMI fue la única técnica de imagen capaz de evaluar morfológica y cuantitativamente las DDO. Conclusiones: RMI es una prometedora modalidad no-invasiva de imagen para diagnosticar DDO superficiales, proporcionando información valiosa sobre la distribución, la ubicación y el tamaño de estas. Por lo tanto, mediante nuestros resultados sugerimos la incorporación de la novedosa técnica de RMI como una herramienta complementaria para el diagnóstico y el seguimiento de DDO en combinación con los otros métodos de imagen multimodales.(AU)

Objective: We aimed to compare the detectability of optic disc drusen (ODD), using various non-invasive imaging techniques, including the novel retro-mode imaging (RMI), as well as to analyze the morphological characteristics of ODD on RMI. Methods: This study involved 7 patients with bilateral ODD, totaling 14 eyes. Multimodal imaging techniques, including multicolor fundus photography (MC), near-infrared reflectance (NIR), green and blue light fundus autofluorescence (G-FAF and B-FAF, respectively), and RMI were used to examine the eyes. FAF was used as the primary method of identifying ODD, and each method's detection rate was compared by two observers. Quantitative measurements of ODD included the number of ODD visualized by the RMI technique, the perimeter (P) and area (A) of ODD were identified. Results: The average age of the patients included was 49.28±23.16 years, with 5 of the 7 being men. RMI was able to detect ODD in all cases, with a sensitivity of 100%, compared to MC (sensitivity 60.71%), NIR (sensitivity 60.71%), B-FAF (sensitivity 100%), G-FAF (sensitivity 100%). RMI was the only imaging technique capable of assessing ODD morphology and quantifying ODD. Conclusions: RMI is a promising imaging modality for diagnosing superficial ODD, providing valuable information on the distribution, location, and size of ODD. We suggest the incorporation of RMI as a complementary tool for diagnosing and monitoring ODD in combination with other multimodal imaging methods.(AU)

Retinal Changes From Hyperopia to Myopia: Not All Diopters Are Created Equal.

Purpose: To quantitatively characterize retinal changes across different quantiles of refractive error in 34,414 normal eyes of 23,064 healthy adults in the UK Biobank. Methods: Twelve optic disc (OD), foveal and vascular parameters were derived from color fundus photographs, correcting for ocular magnification as appropriate. Quantile regression was used to test the independent associations between these parameters and spherical equivalent refraction (SER) across 34 refractive quantiles (high hyperopia to high myopia)-controlling for age, sex and corneal radius. Results: More negative SER was nonlinearly associated with greater Euclidian (largely horizontal) OD-fovea distance, larger OD, less circular OD, more obliquely orientated OD (superior pole tilted towards the fovea), brighter fovea, lower vascular complexity, less tortuous vessels, more concave (straightened out towards the fovea) papillomacular arterial/venous arcade and wider central retinal arterioles/venules. In myopia, these parameters varied more strongly with SER as myopia increased. For example, while every standard deviation (SD) decrease in vascular complexity was associated with 0.63 D (right eye: 95% confidence interval [CI], 0.58-0.68) to 0.68 D (left eye: 95% CI, 0.63-0.73) higher myopia in the quantile corresponding to -0.60 D, it was associated with 1.61 D (right eye: 95% CI, 1.40-1.82) to 1.70 D (left eye: 95% CI, 1.56-1.84) higher myopia in the most myopic quantile. OD-fovea angle (degree of vertical separation between OD and fovea) was found to vary linearly with SER, but the magnitude was of little practical importance (less than 0.10 D variation per SD change in angle in almost all refractive quantiles) compared with the changes in OD-fovea distance. Conclusions: Several interrelated retinal changes indicative of an increasing (nonconstant) rate of mechanical stretching are evident at the posterior pole as myopia increases. These changes also suggest that the posterior pole stretches predominantly in the temporal horizontal direction.

Bilateral optic disc collaterals secondary to high-flow dural arteriovenous fistula: a diagnostic dilemma.

A man in his 80s, with a history of diabetes, hypertension and coronary artery disease, presented with bilateral painless progressive vision loss 2 years prior. His examination showed subnormal best corrected visual acuity of 20/50 and 20/80 in the right eye and left eye (LE), respectively, grade II relative afferent pupillary defect in LE, normal anterior segment, intra-ocular pressure (IOP) and defective colour vision in both eyes (BE). Fundus examination revealed optic disc pallor, disc collaterals and grade 2 hypertensive retinopathy in BE. Automated perimetry showed advanced field loss in BE. MRI of the brain and orbits with contrast showed signs of raised intracranial pressure, and magnetic resonance angiogram of the brain showed multiple arterio-venous channels along with the right transverse and sigmoid sinuses. The patient was referred to a neuroradiologist for further evaluation, and cerebral angiogram confirmed multifocal high-flow dural arterio-venous fistulae at right jugular foramen, transverse and sigmoid sinuses. He underwent Onyx liquid embolization.

Assessment of Time Lag Between Blood Flow, Retinal Nerve Fiber Layer Thickness and Visual Field Sensitivity Changes in Glaucoma.

Purpose: This study investigates the temporal relationship between blood flow changes and alterations in retinal nerve fiber layer thickness (RNFLT) and mean deviation (MD) in individuals with glaucoma. Methods: Blood flow, measured by mean blur rate in optic nerve head vessels (MBRv) and tissues (MBRt) using laser speckle flowgraphy (LSFG)-NAVI, was analyzed using structural equation models (SEMs). SEMs assessed whether the previous rate of one parameter predicted the current rate of the other parameter, adjusted for its own rate in the previous time interval. Data from 345 eyes of 174 participants were gathered from visits every six months. Results: Rates of change of both MBRv and MBRt were significantly predicted by their own rate in the previous time interval and by the rate of change of MD in the previous time interval (P < 0.001 and P = 0.043, respectively), but not by the rate of MD in the concurrent interval (P = 0.947 and P = 0.549), implying that changes in MD precede changes in blood flow. Rates of change of RNFLT were predicted by their own previous rate and the rate of change of MBRv and MBRt in either the previous interval (P = 0.002 and P = 0.008) or the concurrent interval (P = 0.001 and P = 0.018), suggesting that MBR may change before RNFLT. Conclusions: The evidence supports a temporal sequence where MD changes precede blood flow changes, which, in turn, may precede alterations in RNFLT.

Originalbeiträge (Originals). Altered microvascular density in patients with anorexia nervosa ­ an optical coherence tomography angiography (OCTA) pilot study.

OBJECTIVES: To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. Methods:Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls. P-values ≤ 0.0125 were considered statistically significant. Results: VD in the superficialmacular en-face OCTA image was significantly lower in the study group compared to the control group. Neither the deepmacula nor the radial peripapillary capillary (RPC) in the whole-face image nor the RPC-peripapillary imaging appeared to be significantly different. Conclusion: Patients with AN showed reduced VD in the superficialmacular layers compared to healthy controls, which can be discussed as a consequence of the malnutrition. OCTA could be a useful non- invasive tool to detect reduced peripheral blood supply to show vascular changes that occur before ocular symptoms.

Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

Susceptibility of optic nerve head in children with posture-related elevation of intraocular pressure.

BACKGROUND/AIMS: This work aimed to investigate changes in optic nerve head (ONH) morphometry based on Bruch membrane opening in children with extensive nocturnal intraocular pressure (IOP) elevations. METHODS: The course of Bruch membrane opening-based optic nerve head (ONH) morphometry was analysed in thirty-two patients younger than 18 years with evaluable SD-OCT examinations of the ONH and nocturnal posture-dependent IOP elevation above 25 mmHg. Longitudinal changes in neuroretinal rim tissue, as measured by Bruch Membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness, were assessed. RESULTS: One year after the 24 h IOP measurement, global BMO-MRW (- 1.61 ± 16.8 µm, n.s.; p = 0.611) and RNFL (+ 0.64 ± 3.17 µm; n.s.; p = 0.292) measurements were not significantly different from the baseline. No significant BMO-MRW reduction (- 3.91 ± 24.3 µm; n.s. p = 0.458) or deviation in RNFL thickness (+ 1.10 ± 3.52 µm) was observed at the four-year follow-up. Absolute IOP values measured in the supine position did not correlate with changes in global BMO-MRW or RNFL thickness. CONCLUSION: Posture-dependent IOP elevations do not seem to influence retinal nerve fibre layer thickness or Bruch membrane opening-based morphometric data in childhood.

The Temporal Relation Between Rates of Retinal Nerve Fiber Layer and Minimum Rim Width Changes in Glaucoma.

Purpose: This study aims to determine whether OCT-derived rates of change in minimum rim width (MRW) are associated with and can potentially predict corresponding alterations in retinal nerve fiber layer thickness (RNFLT) in people with glaucoma. Methods: The rates of change between six-monthly visits were taken from 568 eyes of 278 participants in the P3 Study. Structural equation models (SEM) assessed whether one parameter was predicted by the concurrent or previous rate of the other parameter, after adjusting for its own rate in the previous time interval. Root mean square error of approximation (RMSEA, with 90% confidence intervals [CI]), Tucker Lewis index (TLI) and the comparative fit index (CFI) assessed goodness of fit. Results: Models without a time lag provided a better fit for the data (RMSEA = 0.101 [CI, 0.089, 0.113]), compared to a model featuring a time lag in RNFLT (RMSEA = 0.114 [CI, 0.102, 0.126]) or MRW (RMSEA = 0.114 [CI, 0.102, 0.127]). The SEMs indicated that rates for both MRW and RNFLT were predicted by their own rate in the previous time interval and by the other measure's change in the concurrent time interval (P > 0.001 for all). No evidence of a clinically significant time lag for either parameter was determined. Conclusions: MRW and RNFLT exhibit concurrent changes over time in patients with glaucoma, with no clinically significant time lag determined. Translational Relevance: RNFLT may be more useful than MRW in early glaucoma assessment because of its previously reported lower variability and reduced sensitivity to intraocular pressure changes.

A method for analyzing AFM force mapping data obtained from soft tissue cryosections.

Atomic force microscopy (AFM) is a valuable tool for assessing mechanical properties of biological samples, but interpretations of measurements on whole tissues can be difficult due to the tissue's highly heterogeneous nature. To overcome such difficulties and obtain more robust estimates of tissue mechanical properties, we describe an AFM force mapping and data analysis pipeline to characterize the mechanical properties of cryosectioned soft tissues. We assessed this approach on mouse optic nerve head and rat trabecular meshwork, cornea, and sclera. Our data show that the use of repeated measurements, outlier exclusion, and log-normal data transformation increases confidence in AFM mechanical measurements, and we propose that this methodology can be broadly applied to measuring soft tissue properties from cryosections.

Validation of retinal oximetry vessel selection using fluorescein angiography in patients with optic disc drusen.

Retinal oximetry could provide insights into the pathophysiology of optic nerve disease, including optic disc drusen (ODD). Vessel selection for oximetry analysis is based on morphological characteristics of arterioles and venules and supported by an overlay of estimated blood oxygen saturations. The purpose of this cross-sectional study was to determine the validity of this vessel selection procedure by comparing it with vessel selection supported by video fluorescein angiography (FA). The study included 36 eyes of 36 patients with ODD who underwent retinal oximetry (Oxymap retinal oximeter T1) followed by FA (Heidelberg Spectralis). Two trained graders selected vessel segments in a pre-defined measurement area around the optic disc. One of these graders additionally performed the vessel segment selection with the support of FA images. When performed by the same grader, FA-supported and non-FA-supported vessel selection did not lead to significant differences in total vessel segment length, estimated oxygen saturations or vessel diameters (all p > 0.05). Inter-grader differences were found for arterial and venous segment lengths and arterial saturation (p < 0.05). A similar tendency was found for the arteriovenous saturation difference (p = 0.10). In conclusion, identifying vessel segments for retinal oximetry analysis based on vessel morphology and supported by a color-coded saturation overlay appears to be a valid method without the need for invasive angiography. A numerically small inter-grader variation may influence oximetry results. Further studies of retinal oximetry in ODD are warranted.

Longitudinal changes in optic disc cupping from the baseline in chiasmal lesion optic neuropathy and glaucoma.

We aimed to investigate the changes in cupping in chiasmal lesion optic neuropathy (chON) compared to baseline optic disc and glaucoma. We used a novel study design to enroll patients who had fundus photographs incidentally taken during routine health check-ups prior to the onset of optic neuropathy. In 31 eyes (21 patients) with chON and 33 eyes (30 patients) with glaucoma, we investigated the change in cup-to-disc (C/D) area from the baseline to overt cupping using flicker analysis. Compared to the baseline, 23 eyes (74.2%) had increased cup size and 3 (9.7%) had vascular configuration changes in the chONgroup; in contrast, all glaucoma eyes exhibited changes in cup size and vascular configuration. The increase in C/D area ratio was significantly smaller in chON (0.04 ± 0.04) compared to glaucoma (0.10 ± 0.04, P < 0.001); the minimum residual neuroretinal rim width showed a more pronounced difference (29.7 ± 8.2% vs 7.1 ± 3.9%, P < 0.001). The changes distributed predominantly towards the nasal direction in chON, contrasting the changes to the arcuate fibers in glaucoma. In conclusion, our results provide the first longitudinal evidence of true pathological cupping in chONcompared to photographically disease-free baseline. The marked difference in the residual minimum rim width reaffirms the importance of rim obliteration in the differential diagnosis between the two diseases.