Cell Layer Thickness Research Articles

Correlations between Steady-State Pattern Electroretinogram and Humphrey Visual Field Analyzer Global Indices and Their Associations with Retinal Ganglion Cell Layer-Inner Plexiform Layer Thickness in Glaucoma Suspects.

The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression.

Discrimination ability of central visual field testing using stimulus size I, II, and III and relationship between VF findings and macular ganglion cell thickness in chiasmal compression.

To compare the relationship between macular ganglion cell layer (mGCL) thickness and 10-2 visual field (VF) sensitivity using different stimulus sizes in patients with temporal hemianopia from chiasmal compression. A cross-sectional study was conducted involving 30 eyes from 25 patients with temporal VF loss on 24-2 SITA standard automated perimetry due to previous chiasmal compression and 30 healthy eyes (23 controls). Optical coherence tomography (OCT) of the macular area and 10-2 VF testing using Goldmann stimulus size I (GI), II (GII), and III (GIII) were performed in the Octopus 900 perimeter. For the sake of analysis, mGCL thickness and VF data were segregated into four quadrants (two temporal and two nasal) and two halves (temporal and nasal) centered on the fovea, in order to evaluate separately both the severely affected nasal hemi-retina corresponding to the temporal VF sectors and the subclinically affected temporal hemi-retina corresponding to the nasal VF sectors. Data from patients and controls were compared using generalized estimated equations. The discrimination ability of GI, GII, and GIII was evaluated, as was the correlation between mGCL and 10-2 VF sensitivity using GI, GII, and GIII. All mGCL parameters in the nasal and temporal halves of the retina were significantly reduced in patients compared to controls. 10-2 VF test sensitivity using GI, GII, and GIII was significantly lower in patients than in controls (p≤0.008) for all parameters, except the three nasal divisions when using GI (p = 0.41, 0.07 and 0.18) Significant correlations were found between temporal VF sectors (all stimulus sizes) and the corresponding nasal mGCL measurements, with similar discrimination ability. Significant correlations were also observed between all three nasal VF divisions and the corresponding temporal mGCL thickness when using stimulus sizes I and II, but not stimulus size III. On 10-2 VF testing, GII outperformed GI and GIII with regard to discrimination ability and structure-function correlation with mGCL thickness in the subclinically affected nasal part of the VF in patients with chiasmal compression. Our findings suggest that the use of GII can enhance the diagnostic power of 10-2 VF testing in early cases of chiasmal compression, although further studies are necessary to support this conclusion.

Assessment of metacognition and retinal optical coherence tomography findings in shift workers

ABSTRACT It is known that working in the shift system, especially the night shift, affects physical, mental, and social well-being. We investigated the changes in the inner retinal layers and choroidal layer of the eyes of nurses working night and day shifts using optical coherence tomography (OCT). We also explored the effect of night shift work on metacognition and the relationships between these variables. A total of 79 nurses participated in the study, of whom 40 worked night shifts. The researcher gave the participants sociodemographic information and the Metacognition Questionnaire-30 (MCQ-30) form. Retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, inner nuclear layer (INL) thickness, inner plexiform layer (IPL) thickness, central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) were measured with OCT. It was found that the level of metacognitive activity associated with cognitive confidence was higher (p = 0.044) for nurses who worked night shifts and that the level of metacognitive activity associated with cognitive awareness was lower (p = 0.015) for nurses who worked night shifts. RNFL-nasal superior (NS) thickness was lower in night shift workers than the day shift group (p = 0.017). Our study revealed significant relationships between metacognition and the OCT findings among night and day shift workers. Our study revealed that RNFL measurements and metacognitive activity may differ and there may be a relationship between these parameters in nurses who work shifts. Further research is needed to investigate the long-term effects of night shift work on retinal health.

Cerebroprotective effects of khellin: validation through computational studies in a bilateral common carotid artery occlusion/reperfusion (BCCAO/R) model

ABSTRACT This study investigates the molecular interactions between khellin and nitric oxide synthase, which plays a significant role in the pathophysiology of acute ischemic stroke. Molecular docking, dynamic simulation, and in vivo approaches were used to explore these interactions, revealing that khellin has a superior binding affinity for nitric oxide synthase compared to its co-crystallized ligand. The cerebroprotective effect of khellin was evaluated in a rat model of cerebral stroke induced by bilateral common carotid artery occlusion and reperfusion (BCCAO/R), and the results showed that khellin treatment significantly decreased infarct size, increased antioxidant levels, decreased oxidative stress, and improved EEG function. Histological analysis also revealed increased pyramidal cell layer thickness and reduced apoptosis in the hippocampus. These findings suggest that khellin may be a promising therapeutic agent for cerebral ischemia by targeting the nitric oxide synthase-nitric oxide pathway.

Avaliação do endotélio corneano através de microscopia especular em participantes com edema macular diabético

Introduction: While the morphological and functional integrity of the corneal endothelium, which is essential for corneal transparency, is affected by diabetes mellitus (DM), its relationship with the severity of diabetic retinopathy and the presence of diabetic macular edema is unclear. Aims: To assess the morphological characteristics of the corneal endothelium in patients with Type 2 Diabetes Mellitus (T2DM) with different therapeutic response profiles to diabetic macular edema (DME). Methods: With a cross-sectional approach, 24 participants with T2DM were divided into 2 groups (without DME versus with DME). Subsequently, the group with DME was subdivided according to the type of therapeutic response (responder versus persistent). Parameters obtained through specular microscopy (endothelial cell density, coefficient of variation, hexagonality, and central corneal thickness) and optical coherence tomography (minimum foveal thickness, central 1mm thickness, macular ganglion cell layer thickness, and peripapillary retinal nerve fiber layer thickness) were analyzed and compared in the different groups. Results: No significant changes were found in the corneal endothelium between the groups with and without DME (p>0.05). However, differences were found in the density of endothelial cells (p=0.04) in participants with persistent DME (1900.3 ± 270.1) compared to participants with responding DME (2307.9 ± 121.2) and control group (2191.7 ± 165.5). Conclusion: There were no differences in the different parameters of the corneal endothelium between participants with and without DME. However, the kind of therapeutic response to DME seems to be associated with a decrease in endothelial cell density.

Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.

Temporal-to-Nasal Macular Ganglion Cell and Inner Plexiform Layer Ratios in a Large Adult Twin Cohort:Correlations With Age and Heritability.

Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.

Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

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.

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. 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. 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. 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.

Posterior segment parameters after uveitic cataract surgery: A prospective study with 1-year results

PurposeTo evaluate the changes in posterior segment after uncomplicated cataract surgery in uveitic patients. MethodsRetinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), central macular thickness (CMT), and choroidal thickness (CT) of 38 eyes of 28 patients were measured pre- and postoperatively on day 1, week 1, and month 1, 3, 6, 9, and 12. ResultsThe RNFLT increased after surgery. Although the measurements taken were higher than the baseline CMT at all postoperative times, no significant difference was detected between the paired comparisons. The GCLT was found to be higher than the baseline value in all quadrants at the 12th month. A decrease in CT was observed at 5 measured points on the 1st day compared to the baseline. ConclusionDuring the 1-year follow-up, the effect of cataract surgery on the retina and choroid in uveitic eyes was most evident at the postoperative month 1.

AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype–Phenotype Characterization Compared to OPA1 Patients

PurposeHeterozygous mutations in AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated to isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DesignCross-sectional study. MethodsThe following neuro-ophthalmological parameters were collected: Log MAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness at optic coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and gender-matched group of OPA1 patients with 1:2 ratio. All eyes were analysed using Clustered Wilcoxon rank sum test using Rosner-Glynn-Lee method. Results44 eyes from 23 ACO2 and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (p=0.029, p=0.023), average (p=0.012, p=0.0007) and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. ConclusionsClinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems associated to an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and resulted virtually indistinguishable from classic OPA1-DOA.

Dual effects of gonadotropin-inhibitory hormone on testicular development in prepubertal Minxinan Black rabbits (Oryctolagus cuniculus).

Gonadotropin-inhibitory hormone (GnIH) is a neurohormone that not only suppresses reproduction at the brain level but also regulates steroidogenesis and gametogenesis at the gonad level. However, its function in gonadal physiology has received little attention in rabbits. The main objective of this study was to evaluate the effects of GnIH on testicular development and function in prepubertal Minxinan Black rabbits (Oryctolagus cuniculus). In the present study, we investigated the serum reproductive hormone concentration, testicular parameters, morphology of seminiferous tubules, apoptosis of testicular cells, and expression of reproductive-related genes in male prepubertal Minxinan Black rabbits intraperitoneally administered with 0, 0.5, 5, or 50 μg quail GnIH-related peptides (qGnIH) for 10 days. Compared with the vehicle, administration with 5 μg of qGnIH downregulated the serum testosterone concentration and mRNA levels of spermatogenic genes (PCNA, FSHR, INHβA, HSF1, and AR) and upregulated the apoptosis rate of testicular cells; administration with 50 μg of qGnIH decreased the serum testosterone concentration and hypothalamic GnIH gene mRNA level and increased the serum LH concentration, pituitary LHβ gene mRNA level, testicular weight, gonadosomatic index (GSI), and spermatogenic cell layer thickness. It is concluded that GnIH could exert dual actions on testicular development depending on the male prepubertal rabbits receiving different intraperitoneal doses.

Compound Danshen dripping pills prevent early diabetic retinopathy: roles of vascular protection and neuroprotection.

Introduction: Diabetic retinopathy (DR) represents a major cause of adult blindness, and early discovery has led to significant increase in the number of patients with DR. The drugs currently used for treatment, such as ranibizumab, mainly focus on the middle and late periods of DR, and thus do not meet the clinical need. Here, the potential mechanisms by which compound Danshen Dripping Pills (CDDP) might protect against early DR were investigated. Methods: Db/db mice were used to establish a DR model. The initial weights and HbA1c levels of the mice were monitored, and retinal pathology was assessed by hematoxylin-eosin (HE) staining. The vascular permeability of the retina and thickness of each retinal layer were measured, and electroretinogram were performed together with fundus fluorescein angiography and optical coherence tomography. The levels of inflammatory factors were examined in retinal tissue, as well as those of intercellular adhesion molecule 1 (ICAM-1), IL-6, and monocyte chemoattractant protein 1 (MCP-1) in the serum using ELISA. Immunohistochemistry was used to evaluate levels of vascular endothelial growth factor (VEGF), B-cell lymphoma 2 (Bcl-2), and Bclassociated X protein (Bax). Retinal cell injury and apoptosis were examined by TdT-mediated dUTP Nick End Labeling (TUNEL) assays. Results: The data showed that CDDP significantly improved cellular disarrangement. Imaging data indicated that CDDP could reduce vascular permeability and the amplitude of oscillatory potentials (OPs), and restore the thickness of the ganglion cell layer. Moreover, CDDP reduced the expression levels of inflammatory factors in both the retina and serum. Conclusion: These findings strongly suggest that CDDP prevents early DR through vascular and neuroprotection.

Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice.

To investigate the impacts of angiotensin II (Ang II) on retinal artery changes in apolipoprotein E deficient (apoE-/-) mice. apoE-/- male mice were infused by minipumps with Ang II at 1000 ng/kg·min (Ang II group) or saline (control group) for 28d. They were underwent ophthalmic fundus examination on day 0, 14, and 28 of infusion. Histopathologic examination, ribonucleic acid (RNA) sequencing and local Ang II measurement of retinas were conducted. Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28. Optical coherence tomography revealed the ganglion cell and inner plexiform layer (GCIPL) thickness in the control group was significantly thinner than that in Ang II group (P<0.001). Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group. Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions, including increased swelling, roughness, disorganization of the retinal vasculature, and vacuoles formation. RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II. The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group (P=0.086). Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE-/- mice, causing aggravation of atherosclerotic lesions, more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Sectorial Ganglion Cell Complex Thickness as Biomarker of Vision Outcome in Patients With Dominant Optic Atrophy.

Dominant optic atrophy (DOA) is an inherited condition caused by autosomal dominant mutations involving the OPA-1 gene. The aim of this study was to assess the relationship between macular ganglion cell and inner plexiform layer (GC-IPL) thickness obtained from structural optical coherence tomography (OCT) and visual outcomes in DOA patients. The study recruited 33 patients with confirmed OPA-1 heterozygous mutation and DOA. OCT scans were conducted to measure the GC-IPL thickness. The average and sectorial Early Treatment Diabetic Retinopathy Study (ETDRS) charts (six-sector macular analysis to enhance the topographical analysis) centered on the fovea were considered. Several regression analyses were carried out to investigate the associations between OCT metrics and final best-corrected visual acuity (BCVA) as the dependent variable. The mean BCVA was 0.43 ± 0.37 logMAR, and the average macular GC-IPL thickness was 43.65 ± 12.56 µm. All of the GC-IPL sectors were significantly reduced and correlated with BCVA. The univariate linear regression and the multivariate stepwise regression modeling showed that the strongest association with final BCVA was observed with the internal superior GC-IPL thickness. Dividing patients based on BCVA, we found a specific pattern. Specifically, in patients with BCVA ≤ 0.3 logMAR, the external superior and inferior sectors together with the internal superior were more significant; whereas, for BCVA > 0.3 logMAR, the external superior sector and internal superior sector were more significant. The study identified OCT biomarkers associated with visual outcomes in DOA patients. Moreover, we assessed a specific OCT biomarker for DOA progression, ranging from patients in the early stages of disease with more preserved GC-IPL sectorial thickness to advanced stages with severe thinning.

Comparison of retinal parameters between rhesus and cynomolgus macaques.

Nonhuman primates are important research models for basic vision research, preclinical pathogenesis, and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between 10 healthy normal rhesus macaques (Macaca mulatta) and 10 cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The Heidelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinograms (mfERGs), and full-field electroretinograms (ff-ERGs). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thicknesses of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave was lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cell activity) and light-adapted 30-hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species, while the times to peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit times of the a- and b-waves in light-adapted 3.0 ERG (the single-flash cone response) were substantially different. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.

An analytical longitudinal observational study on the association of Vitamin D insufficiency in subjects with primary (idiopathic) demyelinating optic neuritis using visual evoked potential and optical coherence tomography

Background: Optic neuritis (ON) is an acute and often immune-mediated inflammatory condition of the optic nerve. Vitamin D acts as an anti-inflammatory agent and may confer neuroprotection. Visual evoked potential (VEP) and optical coherence tomography (OCT) are emerging tools for demyelinating diseases. Aims and Objectives: We tried to correlate between Vitamin D insufficiency and acute demyelinating ON using different parameters such as VEP, ganglion cell layer (GCL) thickness, and retinal nerve fiber layer (RNFL) thickness. Materials and Methods: This observational longitudinal analytical study included thirty non-consecutive patients with primary ON and 30 healthy controls. All patients with ON underwent detailed clinical and ophthalmological examination, and detailed blood workup, including serum 25 (OH) Vitamin D. VEP P100 latency, amplitude, OCT, RNFL thickness, and GCL thickness at presentation and after 3 months from May 2019 to November 2020. Results: Vitamin D insufficiency (below 30 ng/mL) was present in 60% of cases of ON. The baseline VEP showed significantly prolonged P100 latency in affected eyes in the Vitamin D insufficient group (mean 129.78±7.97 ms vs. 121.0±4.99 ms) whereas the P100 amplitude was not significantly altered between the two groups (5.5±3.13 μV vs. 7.08±3.01 μV). The baseline RNFL thickness (132.21±10.69 μm vs. 118.01±10.4 μm) and GCL thickness (76.82±2.04 μm vs. 73.06±3.2 μm) were greater in affected eyes of vitamin D insufficiency ON. There was greater RNFL thinning (79.93±3.42 μm vs. 74.80±3.5 μm) and GCL thinning (64.78±1.9μm vs. 69.02±2.22 μm) in affected eyes of ON with Vitamin D insufficiency at 3 months. Conclusion: Vitamin D insufficiency was found in most cases of ON. Insufficient Vitamin D positively correlated with optic nerve affection severity as evidenced by significantly increased baseline thickness of RNFL and GCL and more thinning of RNFL and GCL at the end of 3 months of follow-up.

Structurally enhanced perimetric examination

Aims/Purpose: To assess the use of structural data to guide perimetric examination.Methods: Two perimetric strategies were tested on ten healthy participants: standard ZEST with population‐based prior distributions and Structural‐ZEST (S‐ZEST), enhanced with OCT data to determine the starting parameters. Both strategies were tested twice, in random order. The Compass Automated Perimeter (CMP, iCare) was used to collect the perimetric data through the Open Perimetry Interface and bespoke Shiny user interface (UI). The UI was used to import the Spectralis SD‐OCT scans (Heidelberg Engineering, Germany) and align the OCT data with the fundus image captured by the CMP. A 10–2 grid was centred on the fovea of each participant, aligned with the fovea‐disc axis. The UI calculated the Ganglion Cell Layer (GCL) thickness corresponding to each test location, after accounting for ganglion cell displacement. The starting priors for S‐ZEST were modelled using an independent dataset of glaucoma and healthy subjects. Bland–Altman plots were used to quantify test–retest variability. Bootstrap was used to calculate confidence intervals (CIs) and p‐values to compare the widths of the 95%‐Limits of Repeatability (LoR). Correlation between GCL thickness and sensitivity (dB) and the difference in test duration was calculated using linear mixed effect models. Agreement was quantified with the mean difference between the results of the two strategies.Results: 95%‐LoRs for S‐ZEST of the two devices were similar (p = 0.829). The structure–function correlation was significant for both (p &lt; 0.001), and very similar between S‐ZEST (R2 = 0.24) and ZEST (R2 = 0.23). There was a small but statistically significant mean difference in sensitivity between S‐ZEST and ZEST (0.56 [0.35, 0.77] dB, p = 0.034). S‐ZEST was 2.7 [1.2, 3.5] min faster than ZEST (p &lt; 0.001).Conclusions: S‐ZEST significantly shortened testing time without reducing repeatability in healthy observers.

Associations of neurovascular dysfunction with inner retinal layer thickness in non‐proliferative diabetic retinopathy

Aims/Purpose: Neurovascular dysfunction and inner retinal layer thinning are among the earliest detectable retinal changes in diabetes, and both worsen during development and progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyse associations between the retinal functional hyperaemic response and thickness of the individual neuroretinal layers in eyes with non‐proliferative DR.Methods: Thirty patients with Type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non‐proliferative DR and 14 healthy subjects were included in this cross‐sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyser. Individual retinal layer thickness in the macula was analysed from spectral domain optical coherence tomography.Results: Flicker light‐induced vessel dilation was significantly reduced in diabetes patients compared to healthy controls (veins: 3.0% vs. 6.1%, p &lt; 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010) and inner plexiform layer thickness (r = 0.40, p = 0.027), and negatively with haemoglobin A1c (HbA1c) levels (r = −0.41, p = 0.023) and age (r = −0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only HbA1c (p = 0.027, β = −0.40) and GCL thickness (p = 0.030, β = 0.39) remained significantly associated with the vascular flicker light response.Conclusions: The results indicate that thinner GCL and worse glycaemic control both contribute to reduced neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.

Risk factors and macular microvascular changes in open angle glaucoma progression: A longitudinal study using OCT‐A

Aims/Purpose: To investigate prospectively macular microvascular changes in patients with glaucoma and identify common characteristics among the progressive eyes.Methods: A 12‐month prospective longitudinal study was performed with 124 open‐angle‐glaucoma‐eyes (GE). Glaucomatous progression was defined as a decrease of ≥5 μm in average or ≥7 μm in a sector of RNFL thickness. OMAG OCT microangiography (Angioplex, HD OCT, Cirrus 5000, Zeiss) was used to analyse the macular region. The statistical analysis was performed using the SPSS version 23.0 statistical package (SPSS Inc., IL).Results: Among the GE group, 22.36% of eyes showed progression, being the decrease of the Complete Region Macular Vessel Density (MVD) and Macular Capillary Perfusion Density (MPD) greater (−1.14 mm/mm2 and −3.18%) compared to non‐progressive eyes (−0.42 mm/mm2 and −1.02%) [p = 0.123 and 0.057], being the temporal and superior sectors for both MVD and MPD, the ones that showed greater differences (−1.44 mm/mm2, −1.11 mm/mm2, −3.6% and −2.95% respectively) [p &gt; 0.05 for all]. Characteristics as elevated intraocular pressure (IOP) (17.29 vs 14.87 mmHg), thinner central corneal thickness (CCT) (521.53 vs 538.65 μm) and lower ocular perfusion pressure (OPP) (45.88 vs 49.21 mmHg) were significantly different in those progressive GE [p &lt; 0′05 for all]. Nevertheless, increased vertical cup to disc ratio (CDV) (0.64 vs 0.63) and minimum ganglion cell layer thickness (GCLM) (58,82 vs 56.51 μm) were not significantly different in progressive GE [p = 0.768 and 0.249].Conclusions: Data showed that when glaucomatous progression took place, stronger vascular changes occurred in the macular area, as greater decrease of MVD and MPD specially in the temporal and superior sectors. In addition, common characteristics as elevated intraocular pressure, thinner central corneal thickness and lower ocular perfusion pressure were identified in progressive GE. Nevertheless, further research with larger population and larger follow‐up is needed to obtain stronger results.