Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

Diagnostic ability of the combination of retinal microvasculature evaluation and static automated perimetry for early primary open-angle glaucoma.

PURPOSE: To investigate the diagnostic ability of retinal superficial vasculature evaluation by optic coherence tomography angiography (OCTA) combined with visual field (VF) testing for early primary open-angle glaucoma (POAG). PATIENTS AND METHODS: In this cross-sectional study, 84 participants were included, including 11 in the ocular hypertension (OHT) group, 11 in the preperimetric POAG (pre-POAG) group, 29 in the early POAG group and 33 in the control group. All participants underwent 6 × 6 mm2 scans of macula and optic nerved head by optic coherence tomography (OCT) and OCTA, along with white-on-white and blue-on-yellow VF testing by static automated perimetry. The ability of diagnosing early glaucoma by either various examinations separately or combination of examinations in both terms of function and structure was studied using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: The superficial retinal vessel densities (VD) in peri-nasal, para-temporal, peri-temporal and peri-inferior regions around the macula, as well as vessel area densities (VAD) in all peripapillary regions, were significantly different among the four groups, with lower VD or VAD in the early POAG patients compared to the normal individuals. The diagnostic ability of peripapillary superficial retinal VAD alone or VF testing alone was limited for early POAG only. However, the combination of these two was more effective in distinguishing normal individuals from OHT subjects or pre-POAG patients without VF defects, with better performance than the combination of peripapillary retinal nerve fiber layer (RNFL) thickness and VF indicators. CONCLUSIONS: Peripapillary retinal vessel densities were generally lower in early POAG patients compared to normal individuals. The combination of peripapillary superficial retinal VAD by OCTA with white-on-white VF testing improved the ability to distinguish POAG patients at early stage without function impairment, which may help in providing reference and guidance for the following-up and treatment of suspected POAG patients.

Case report: Unilateral papilledema in a dog with a large suprasellar mass and suspected intracranial hypertension: insights from funduscopy, optical coherence tomography, and magnetic resonance imaging.

A spayed, 8-year-old female Poodle, weighing 5.7 kg, was presented with the chief complaint of vision impairment. Vision assessment, including pupillary light reflexes, menace response, dazzle reflex, and maze navigation in photopic and scotopic circumstances, revealed a negative response in both eyes except for positive direct pupillary light reflex in the right eye and positive consensual pupillary light reflex from the right eye to the left eye. Systemic evaluation, including neurologic status, blood profile, and thoracic radiographs, did not reveal any abnormalities. Complete ophthalmic examinations, ocular ultrasonography, and electroretinography did not identify a cause of blindness. Upon funduscopy, the left eye exhibited an increased optic disk diameter, blurred optic disk borders, and loss of the physiologic pit, as well as an increase in vascular tortuosity. In the right eye, there were multifocal depigmented areas in the non-tapetal fundus and several pigmented spots surrounded by a region of dull tapetal reflection in the tapetal fundus. The optical coherence tomography revealed severe anterior deformation of the optic nerve head and Bruch's membrane in the peripapillary region of the left eye. Magnetic resonance imaging revealed an irregular, broad-based suprasellar mass, with features suggestive of intracranial hypertension, including dorsal displacement of third ventricles, a rightward shift of the falx cerebri, trans-tentorial herniation, perilesional edema, flattening/protrusion of the posterior sclera, and lager optic nerve sheath diameter in left side than right side. This is the first comprehensive report that describes unilateral papilledema in a dog with a brain tumor, using advanced ophthalmic and neuro-imaging modalities.

Assessment of Early Glaucomatous Optic Neuropathy in the Dog by Spectral Domain Optical Coherence Tomography (SD-OCT).

BACKGROUND: Inherited primary open-angle glaucoma (POAG) in Beagle dogs is a well-established large animal model of glaucoma and is caused by a G661R missense mutation in the ADAMTS10 gene. Using this model, the study describes early clinical disease markers for canine glaucoma. METHODS: Spectral-domain optical coherence tomography (SD-OCT) was used to assess nine adult, ADAMTS10-mutant (median age 45.6 months, range 28.8-52.8 months; mean diurnal intraocular pressure (IOP): 29.9 +/- SEM 0.44 mmHg) and three related age-matched control Beagles (mean diurnal IOP: 18.0 +/- SEM 0.53 mmHg). RESULTS: Of all the optic nerve head (ONH) parameters evaluated, the loss of myelin peak height in the horizontal plane was most significant (from 154 +/- SEM 38.4 µm to 9.3 +/- SEM 22.1 µm; p < 0.01). There was a strong significant negative correlation between myelin peak height and IOP (Spearman correlation: -0.78; p < 0.003). There were no significant differences in the thickness of any retinal layers evaluated. CONCLUSIONS: SD-OCT is a useful tool to detect early glaucomatous damage to the ONH in dogs before vision loss. Loss in myelin peak height without inner retinal thinning was identified as an early clinical disease marker. This suggests that initial degenerative changes are mostly due to the loss of myelin.

How is eyeball growth associated with optic nerve head shape and glaucoma? The Lamina cribrosa/Bruch's membrane opening offset theory.

The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma.

Exploring the utility of retinal optical coherence tomography as a biomarker for idiopathic intracranial hypertension: a systematic review.

This study aimed to examine the existing literature that investigated the effectiveness of optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) as a biomarker for idiopathic intracranial hypertension (IIH). Our search was conducted on January 17th, 2024, and included the databases, Medline, Scopus, Embase, Cochrane, Latin American and Caribbean Health Sciences Literature (LILACS), International Standard Randomized Controlled Trial Number (ISRCTN) registry, and the International Clinical Trials Registry Platform (ICTRP). Our final review included 84 articles. In 74 studies, OCT was utilized as the primary ocular imaging method, while OCT-A was employed in two studies including eight studies that utilized both modalities. Overall, the results indicated that IIH patients exhibited significant increases in retinal nerve fiber layer (RNFL) thickness, total retinal and macular thickness, optic nerve head volume, and height, optic disc diameter and area, rim area, and thickness compared to controls. A significant correlation was observed between cerebrospinal fluid (CSF) pressure and OCT parameters including RNFL thickness, total retinal thickness, macular thickness, optic nerve head volume, and optic nerve head height. Interventions aimed at lowering CSF pressure were associated with a substantial improvement in these parameters. Nevertheless, studies comparing peripapillary vessel density using OCT-A between IIH patients and controls yielded conflicting results. Our systematic review supports OCT as a powerful tool to accurately monitor retinal axonal and optic nerve head changes in patients with IIH. Future research is required to determine the utility of OCT-A in IIH.

Multimodal Imaging of Optic Nerve Head in Retinitis Pigmentosa.

BACKGROUND: A pallor optic nerve head (ONH) is one of the three features of retinitis pigmentosa (RP). This study aimed to assess the ONH prospectively by color tone, presence of hyper-reflective tissue, blood flow, retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) and investigate the change in these parameters with and without ONH pallor. METHODS: The presence of ONH pallor was assessed by three independent examiners through careful examination using fundus photographs. The presence of a hyper-reflective structure on the ONH was carefully evaluated using a volume scan optical coherence tomography (OCT). RNFL thickness and ellipsoid zone (EZ) width around the macula were also evaluated by OCT. Laser speckle flowgraphy was used to measure the mean blur rate of the entire ONH area, which was subsequently divided into the vessel area (MV) and tissue area (MT). RESULTS: Twenty-eight eyes of 28 patients with RP (55.4 ± 16.23 years of age) were included. The pale ONH was observed in 10 (35%) eyes. Hyper-reflective structures were observed in seven (25%) eyes. No significant correlation was found between the pale ONH and the presence of a hyper-reflective structure (Pearson's chi-squared test, p = .364). The average of the ONH area, MV, and MT was 8.65 ± 3.08 AU, 17.81 ± 7.54 AU, and 6.4 ± 2.66 AU, respectively, which significantly decreased in patients with pallor ONH (all p < .05). The global RNFL thickness was 73.54 ± 18.82 µm. The nasal and superior quadrants and global RNFL thickness in patients with a pale ONH were significantly thinner than in patients without a pale ONH (all p < .05). The global and superior and inferior GCC thickness in patients with a pale ONH were significantly thinner than in patients without a pale ONH(all p < .05).There was no difference in the EZ width between patients with and without a pale ONH (p = .107). CONCLUSION: We conducted multiple assessments of the ONH in RP patients and investigated its clinical significance. Our findings suggest that ONH pallor may indicate a comprehensive change that emerges alongside the progression of retinal degeneration in RP. TRIAL REGISTRATION: This trial was retrospectively registered in the UMIN Clinical Trial Registry (UMIN ID: 000048168).

Repeatability, interocular correlation and agreement of optic nerve head vessel density in healthy eyes: a swept-source optical coherence tomographic angiography study.

AIM: To assess the repeatability, interocular correlation, and agreement of quantitative swept-source optical coherence tomography angiography (OCTA) optic nerve head (ONH) parameters in healthy subjects. METHODS: Thirty-three healthy subjects were enrolled. The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm ×3 mm scanning protocol. Images of the radial peripapillary capillary were analyzed by a customized Matlab program, and the vessel density, fractal dimension, and vessel diameter index were measured. The repeatability of the four scans was determined by the intraclass correlation coefficient (ICC). The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient, ICC and Bland-Altman plots. RESULTS: All swept-source-OCTA ONH parameters exhibited certain repeatability, with ICC>0.760 and coefficient of variation (CoV)≤7.301%. The obvious interocular correlation was observed for papillary vessel density (ICC=0.857), vessel diameter index (ICC=0.857) and fractal dimension (ICC=0.906), while circumpapillary vessel density exhibited moderate interocular correlation (ICC=0.687). Bland-Altman plots revealed an agreement range of -5.26% to 6.21% for circumpapillary vessel density. CONCLUSION: OCTA ONH parameters demonstrate good repeatability in healthy subjects. The interocular correlations of papillary vessel density, fractal dimension and vessel diameter index are high, but the correlation for circumpapillary vessel density is moderate.

Postmortem Analysis of Optic Nerve Head Vascularization in an Individual With Glaucoma.

Reduced ocular perfusion likely contributes to glaucomatous damage at the optic nerve head (ONH). In recent decades, investigators have focused heavily on ocular perfusion pressure and other factors affecting blood flow to the eye. Comparatively, far less attention has been focused on the blood vessels themselves. Here, we asked whether glaucomatous individuals exhibit anatomical deficiencies (i.e., fewer blood vessels) in their ONH blood supply. To answer this question, we performed a systematic literature review to (1) determine how many studies have reported measuring blood vessels in the ONH and (2) whether these studies reported differences in blood vessel quantity. Additionally, we report a method for quantifying blood vessels in ex vivo human ONH preparations, including an ONH from an individual with glaucoma. Our results show that only two studies in the past 50 years have published data concerning blood vessel density in glaucomatous ONHs. Interestingly, both studies reported decreased blood vessel density in glaucoma. Consistent with this finding, we also report reduced blood vessel numbers in the superolateral quadrant of a glaucomatous individual's ONH. Vascularity in the three remaining quadrants was similar to control. Together, our findings raise the interesting possibility that individuals with a relatively sparse ONH blood supply are more likely to develop glaucoma. Future studies with larger sample sizes and more thorough quantification are necessary to determine the link more accurately between glaucoma and the blood supply to the ONH.

Optic Nerve Head Pulsatile Displacement in Open-Angle Glaucoma after Intraocular Pressure Reduction Measured by Optical Coherence Tomography: A Pilot Study.

This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma (POAG) patients with and without axial myopia. Forty-one POAG patients (19 without myopia, 9 with axial myopia and 13 glaucoma with no intervention) participated. Swept-source optical coherence tomography (OCT) videos of the ONH were obtained before and after IOP-lowering treatment (medical or surgical) achieving a minimum IOP drop of 3 mmHg. A demons registration-based algorithm measured local pulsatile displacement maps within the ONH. Results demonstrated a significant 14% decrease in pulsatile tissue displacement in the non-myopic glaucoma cohort after intervention (p = 0.03). However, glaucoma patients with axial myopia exhibited no statistically significant change. There were no significant changes in the pulsatile ONH deformation in the control group. These findings suggest a potential link between IOP reduction and reduced pulsatile displacement within the ONH in POAG patients without myopia, offering new insights into the disease's pathophysiology and warranting further investigation into underlying mechanisms and clinical implications.

Transcriptional profiling of retinal astrocytes identifies a specific marker and points to functional specialization.

Astrocyte heterogeneity is an increasingly prominent research topic, and studies in the brain have demonstrated substantial variation in astrocyte form and function, both between and within regions. In contrast, retinal astrocytes are not well understood and remain incompletely characterized. Along with optic nerve astrocytes, they are responsible for supporting retinal ganglion cell axons and an improved understanding of their role is required. We have used a combination of microdissection and Ribotag immunoprecipitation to isolate ribosome-associated mRNA from retinal astrocytes and investigate their transcriptome, which we also compared to astrocyte populations in the optic nerve. Astrocytes from these regions are transcriptionally distinct, and we identified retina-specific astrocyte genes and pathways. Moreover, although they share much of the "classical" gene expression patterns of astrocytes, we uncovered unexpected variation, including in genes related to core astrocyte functions. We additionally identified the transcription factor Pax8 as a highly specific marker of retinal astrocytes and demonstrated that these astrocytes populate not only the retinal surface, but also the prelaminar region at the optic nerve head. These findings are likely to contribute to a revised understanding of the role of astrocytes in the retina.

Early detection of optic nerve head changes using optical coherence tomography after using mesenchymal stromal cells as intravitreal therapy in rabbit models of ocular hypertension.

Background and Aim: Stem cell therapy is considered a promising treatment for several neurodegenerative diseases. However, there are very few studies on the use of this therapy in glaucoma models. By detecting the changes produced by glaucoma early, cell therapy could help prevent the events that lead to blindness. In this study, early changes in the optic nerve head (ONH) as detected by optical coherence tomography (OCT) after the application of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) in an experimental model of ocular hypertension (OH) were evaluated. Materials and Methods: Fifteen New Zealand rabbits were randomly divided into the following three groups: G1: OH, G2: hWJ-MSCs, and G3: OH + hWJ-MSCs. An OH model was constructed, and the intraocular pressure (IOP) was measured regularly. At week 7, 105/100 µL hWJ-MSCs were intravitreally injected. Retinography and OCT were used to evaluate structural changes in ONH. Results: IOP increased significantly in G1 and G3 from week 3 onward. Retinography revealed more significant optic nerve changes, that is, papillary asymmetry suggestive of optic nerve excavation, vascular alterations, and irregular hypopigmentation peripheral to the optic disk margin, in G1 compared with G3. OH locates the hWJ-MSCs solution in the vitreous in front of the optic nerve. OCT revealed retinal nerve fiber layer (RNFL) reduction in all groups, reduced optic cup volume in G2 and G3 between weeks 1 and 9, and significant ganglion cell layer thickness reduction in G1 and a slight increase in G3. Conclusion: Intravitreal hWJ-MSCs injection produced changes in optic cup volume, which were detected early on by OCT; however, RNFL could not be restored in this OH model.

A Noninvasive Clinical Method to Measure in Vivo Mechanical Strains of the Lamina Cribrosa by OCT.

Objective: To measure mechanical strain of the lamina cribrosa (LC) after intraocular pressure (IOP) change produced 1 week after a change in glaucoma medication. Design: Cohort study. Participants: Adult glaucoma patients (23 eyes, 15 patients) prescribed a change in IOP-lowering medication. Intervention: Noninvasive OCT imaging of the eye. Main Outcome Measures: Deformation calculated by digital volume correlation of OCT scans of the LC before and after IOP lowering by medication. Results: Among 23 eyes, 17 eyes of 12 persons had IOP lowering ≥ 3 mmHg (reduced IOP group) with tensile anterior-posterior Ezz strain = 1.0% ± 1.1% (P = 0.003) and compressive radial strain (Err) = -0.3% ± 0.5% (P = 0.012; random effects models accounting inclusion of both eyes in some persons). Maximum in-plane principal (tensile) strain and maximum shear strain in the reduced-IOP group were as follows: Emax = 1.7% ± 1.0% and Γmax = 1.4% ± 0.7%, respectively (both P < 0.0001 vs. zero). Reduced-IOP group strains Emax and Γmax were significantly larger with greater % IOP decrease (P < 0.0001 and P < 0.0001, respectively). The compliances of the Ezz, Emax, and Γmax strain responses, defined as strain normalized by the IOP decrease, were larger with more abnormal perimetric mean deviation or visual field index values (all P ≤ 0.02). Strains were unrelated to age (all P ≥ 0.088). In reduced-IOP eyes, mean LC anterior border posterior movement was only 2.05 µm posteriorly (P = 0.052) and not related to % IOP change (P = 0.94, random effects models). Only Err was significantly related to anterior lamina depth change, becoming more negative with greater posterior LC border change (P = 0.015). Conclusions: Lamina cribrosa mechanical strains can be effectively measured by changes in eye drop medication using OCT and are related to degree of visual function loss in glaucoma. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optic Nerve Head and Retinal Nerve Fiber Layer Analysis in Emmetropic Malay Children.

BACKGROUND AND OBJECTIVES: The study aims to investigate the normal reference values for optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters in emmetropic Malay children, utilizing measurements obtained through Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA). METHODOLOGY: A cross-sectional study was conducted on 95 Malay children, aged between seven and 17 years, with no ocular abnormalities. It was held at Hospital Universiti Sains Malaysia, Malaysia, from January 2014 to December 2015. All children underwent a full ocular examination, including refraction and calculation of axial length. ONH and retinal nerve fiber layer thickness (RNFLT) parameters were measured using the Cirrus SD-OCT machine. One eye of each subject was selected randomly for study. The associations between the parameters and the effect of age, gender, axial length, and spherical equivalent (SE) on the measurements were statistically validated. RESULTS: Ninety-five children were involved in the study, with 65 females (68.4%) and 30 males (31.6%). The mean age was 10.6 (2.82) years, the mean intraocular pressure (IOP) was 14.8 (2.81) mmHg, the mean SE-refraction was 0.12 (0.28) diopters, and the mean axial length was 23.03 (0.76) mm. The mean disc area, rim area, and cup volume were 2.32 (0.40) mm2, 1.53 (0.33) mm2, and 0.204 (0.16) mm3, respectively. The average cup-to-disc ratio (SD) (CDR) and the vertical CDR were 0.55 (0.13) and 0.50 (0.14). Mean (SD) RNFLT was 102.08 (11.08) µm for all patients. There was a strong positive correlation between the average, superior, and inferior RNFLT with the optical disc area. The rim area and the average, superior, inferior, and nasal RNFLT also showed a significant correlation. The inferior RNFLT was negatively correlated with the average CDR. There was also a major influence of gender on the disc area. There were no major age, axial length, and SE influences on the measurements. CONCLUSIONS: This study provided normative information for ONH and RNFLT parameters in emmetropic Malay children. It was observed that emmetropic Malay males exhibited a significantly larger optical disc area. The increase in RNFLT is correlated with a significant increase in disc and rim areas.

Optical Coherence Tomography Angiography Assessment of the Optic Nerve Head in Patients Hospitalized Due to COVID-19 Bilateral Pneumonia.

Background and objectives: We aimed to investigate changes in the radial peripapillary capillary (RPC) network using optical coherence tomography angiography (OCTA) in patients who recovered from coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study of patients hospitalized due to COVID-19 bilateral pneumonia between March and May 2021. The control group included healthy individuals matched for age and sex. Two months after discharge, the patients underwent ophthalmological examination, including optical coherence tomography (OCT) imaging. The RPC network and retinal nerve fiber layer (RNFL) of the optic disc (RNFL optic disc) were automatically evaluated and compared between the study groups. Additionally, the RPC parameters were compared between the men and women in the COVID-19 group, and correlations between the RPC and RNFL optic disc parameters were assessed. Results: A total of 63 patients (120 eyes) with bilateral pneumonia caused by severe acute respiratory syndrome coronavirus 2 infection were examined. No ophthalmic symptoms were reported by the patients. No significant differences were observed in the RPC parameters between the patients from the COVID-19 group and the 43 healthy controls. Moreover, the RPC parameters did not differ between the men and women in the COVID-19 group. A positive correlation was found between the RPC and RNFL optic disc parameters in the COVID-19 patients (p < 0.001). Conclusions: No changes in the RPC network were observed among the patients with COVID-19 bilateral pneumonia in the early period after hospital discharge. However, a longer follow-up is needed to monitor COVID-19-related changes in the microvasculature of the optic nerve head.

Stimulus type and duration affect magnitude and evolution of flicker-induced hyperemia measured by laser speckle flowgraphy at the optic disc and peripapillary vessels.

Neurovascular coupling is a vital mechanism employed by the cerebrovascular system, including the eye, to regulate blood flow in periods of neuronal activation. This study aims to investigate if laser speckle flowgraphy (LSFG) can detect coupling response elicited by flickering light stimuli and how variations in stimulus type and duration can affect the magnitude and evolution of blood flow in the optic nerve head (ONH) and peripapillary vessels. Healthy adults were exposed to two types of 10-Hz flicker stimuli: a photopic negative response-like stimulus (PhNR-S) or a visual evoked potential-like stimulus (VEP-S)-each presented in separate 10- and 60-s epochs. Both PhNR-S and VEP-S significantly increased ONH blood flow (p < 0.001) immediately after flicker cessation, with a trend of 60-s stimuli (PhNR-S = 11.6%; VEP-S = 10.4%) producing a larger response than 10-s stimuli (PhNR-S = 7.5%; VEP-S = 6.2%). Moreover, exposure to 60-s stimuli elicited a significantly prolonged ONH hyperemic response, especially with PhNR-S. Lastly, stimulation with either 60-s stimuli elicited a robust increase in blood flow within the peripapillary arterioles (p < 0.01) and venules (p < 0.01) as well. Flicker stimulation with common visual electrophysiology stimuli (PhNR-S and VEP-S) induced a demonstrable increase in ONH and peripapillary vessel blood flow, which varied with flicker duration. Our results validate that LSFG is a robust method to quantify flicker-induced hyperemic responses and to study neurovascular coupling in humans.

Lysyl oxidase like-1 deficiency in optic nerve head astrocytes elicits reactive astrocytosis and alters functional effects of astrocyte derived exosomes.

Glaucoma is a multifactorial progressive ocular pathology that manifests clinically with damage to the optic nerve (ON) and the retina, ultimately leading to blindness. The optic nerve head (ONH) shows the earliest signs of glaucoma pathology, and therefore, is an attractive target for drug discovery. The goal of this study was to elucidate the effects of reactive astrocytosis on the elastin metabolism pathway in primary rat optic nerve head astrocytes (ONHA), the primary glial cell type in the unmyelinated ONH. Following exposure to static equibiaxial mechanical strain, we observed prototypic molecular and biochemical signatures of reactive astrocytosis that were associated with a decrease in lysyl oxidase like 1 (Loxl1) expression and a concomitant decrease in elastin (Eln) gene expression. We subsequently investigated the role of Loxl1 in reactive astrocytosis by generating primary rat ONHA cultures with ∼50% decreased Loxl1 expression. Our results suggest that reduced Loxl1 expression is sufficient to elicit molecular signatures of elastinopathy in ONHA. Astrocyte derived exosomes (ADE) significantly increased the length of primary neurites of primary neurons in vitro. In contrast, ADE from Loxl1-deficient ONHA were deficient of trophic effects on neurite outgrowth in vitro, positing that Loxl1 dysfunction and the ensuing impaired elastin synthesis during reactive astrocytosis in the ONH may contribute to impaired neuron-glia signaling in glaucoma. Our data support a role of dysregulated Loxl1 function in eliciting reactive astrocytosis in glaucoma subtypes associated with increased IOP, even in the absence of genetic polymorphisms in LOXL1 typically associated with exfoliation glaucoma. This suggests the need for a paradigm shift toward considering lysyl oxidase activity and elastin metabolism and signaling as contributors to an altered secretome of the ONH that may lead to the progression of glaucomatous changes. Future research is needed to investigate cargo of exosomes in the context of reactive astrocytosis and identify the pathways leading to the observed transcriptome changes during reactive astrocytosis.

Heterogenous thinning of peripapillary tissues occurs early during high myopia development in juvenile tree shrews.

Myopia is an independent risk factor for glaucoma, but the link between both conditions remains unknown. Both conditions induce connective tissue remodeling at the optic nerve head (ONH), including the peripapillary tissues. The purpose of this study was to investigate the thickness changes of the peripapillary tissues during experimental high myopia development in juvenile tree shrews. Six juvenile tree shrews experienced binocular normal vision, while nine received monocular -10D lens treatment starting at 24 days of visual experience (DVE) to induce high myopia in one eye and the other eye served as control. Daily refractive and biometric measurements and weekly optical coherence tomography scans of the ONH were obtained for five weeks. Peripapillary sclera (Scl), choroid-retinal pigment epithelium complex (Ch-RPE), retinal nerve fiber layer (RNFL), and remaining retinal layers (RRL) were auto-segmented using a deep learning algorithm after nonlinear distortion correction. Peripapillary thickness values were quantified from 3D reconstructed segmentations. All lens-treated eyes developed high myopia (-9.8 ± 1.5 D), significantly different (P < 0.001) from normal (0.69 ± 0.45 D) and control eyes (0.76 ± 1.44 D). Myopic eyes showed significant thinning of all peripapillary tissues compared to both, normal and control eyes (P < 0.001). At the experimental end point, the relative thinning from baseline was heterogeneous across tissues and significantly more pronounced in the Scl (-8.95 ± 3.1%) and Ch-RPE (-16.8 ± 5.8%) when compared to the RNFL (-5.5 ± 1.6%) and RRL (-6.7 ± 1.8%). Furthermore, while axial length increased significantly throughout the five weeks of lens wear, significant peripapillary tissue thinning occurred only during the first week of the experiment (until a refraction of -2.5 ± 1.9 D was reached) and ceased thereafter. A sectorial analysis revealed no clear pattern. In conclusion, our data show that in juvenile tree shrews, experimental high myopia induces significant and heterogeneous thinning of the peripapillary tissues, where the retina seems to be protected from profound thickness changes as seen in Ch-RPE and Scl. Peripapillary tissue thinning occurs early during high myopia development despite continued progression of axial elongation. The observed heterogeneous thinning may contribute to the increased risk for pathological optic nerve head remodeling and glaucoma later in life.

Functional and perfusion changes associated with silicone oil tamponade after macula-off rhegmatogenous retinal detachment surgery: an optical coherence tomography angiography/microperimetry study.

PURPOSE: The current study utilizes microperimetry and optical coherence tomography angiography (OCTA) to assess the optic nerve head vasculature, retinal microvasculature, and retinal sensitivity before and after silicone oil (SO) removal. METHODS: This prospective observational case series study involved 30 eyes subjected to silicone oil endotamponade. Microperimetry and OCTA were utilized to assess the vascular density (VD) of the macula and optic nerve head, as well as the retinal sensitivity (RS), of the participants preoperatively and 1 month following SO removal. The correlation between the various parameters of OCTA and microperimetry was evaluated. RESULTS: There was a significant improvement in the postoperative best-corrected visual acuity (BCVA) (p-value < 0.001) and the postoperative total RS, which was 6.38 ± 2.34 dB as compared to a mean preoperative total RS of 5.04 ± 2.06 dB (p-value < 0.001) and showing a significant increase in all rings. However, there was no significant difference in the pre and postoperative macular VD. On the other hand, there was a significant increase in the postoperative VD of the whole disk and the peripapillary capillary plexus, p-values < 0.001 and 0.002, respectively. CONCLUSION: The removal of SO resulted in significant improvements in retinal sensitivity, vision, and optic nerve perfusion. However, no significant change was observed in macular VD. CLINICAL TRIALS: gov Identifier: NCT04928196.

Long-term Remodeling Response in the Lamina Cribrosa Years after Intraocular Pressure Lowering by Suturelysis after Trabeculectomy.

OBJECTIVE: To measure the remodeling of the lamina cribrosa (LC) years after intraocular pressure (IOP) lowering by suturelysis. DESIGN: Cohort study. PARTICIPANTS: Glaucoma patients were imaged 20 minutes after laser suturelysis after trabeculectomy surgery and at their follow-up appointment 1 to 4 years later (16 image pairs; 15 persons). INTERVENTION: Noninvasive OCT imaging of the eye. MAIN OUTCOME MEASURES: Deformation calculated by correlating OCT scans of the LC immediately after IOP lowering by suturelysis and those acquired years later (defined as remodeling strain). RESULTS: The LC anterior border moved 60.9 ± 54.6 µm into the eye (P = 0.0007), and the LC exhibited regions of large local stretch in the anterior-posterior direction on long-term, maintained IOP lowering, resulting in a mean anterior-posterior remodeling strain of 14.0% ± 21.3% (P = 0.02). This strain and the LC border movement was 14 times and 124 times larger, respectively, than the direct response to IOP lowering by suturelysis. A larger anterior LC border movement was associated with greater mean anterior-posterior remodeling strain (P = 0.004). A thinner retinal nerve fiber layer at suturelysis was also associated with greater mean anterior-posterior remodeling strain at follow-up (P = 0.05). Worsening visual field indexes during follow-up were associated with a greater mean circumferential remodeling strain (P = 0.02), due to regions of large local circumferential stretch of the LC. Eyes with a more compliant LC torsional shear strain response at lysis were associated with worse mean deviation at follow-up (P = 0.03). CONCLUSIONS: Strains and LC border position changes measured years after IOP lowering are far larger than the immediate response to IOP lowering and indicate dramatic remodeling of the LC anatomical structure caused by IOP lowering and glaucoma progression. The remodeling strains indicate substantial local stretch in the anterior-posterior direction and are associated with movement of the LC anterior border into the eye. Eyes with greater direct strain response to IOP lowering, greater glaucoma damage at suturelysis, and greater worsening of visual field at follow-up experienced greater remodeling. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03267849. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.