Inner Plexiform Research Articles

High-Density Optical Coherence Tomography Analysis Provides Insights Into Early/Intermediate Age-Related Macular Degeneration Retinal Layer Changes.

PurposeTo topographically map all of the thickness differences in individual retinal layers between early/intermediate age-related macular degeneration (AMDearly/AMDint) and normal eyes and to determine interlayer relationships.MethodsNinety-six AMDtotal (48 AMDearly and 48 AMDint) and 96 normal eyes from 192 participants were propensity-score matched by age, sex, and refraction. Retrospective optical coherence tomography (OCT) macular cube scans were acquired, and high-density (60 × 60 0.01-mm2) grid thicknesses were custom extracted for comparison between AMDtotal and normal eyes corrected for confounding. Resultant “normal differences” underwent cluster, interlayer correlation, and dose–response analyses for the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer + Henle's fiber layer (ONL+HFL), inner and outer segment (IS/OS) thickness, and retinal pigment epithelium (RPE) to Bruch's membrane (BM) thickness.ResultsAMDtotal inner retinal clusters demonstrated extensively thinned RNFL, GCL, IPL, and paracentral INL and thickened INL elsewhere, with normal difference means ranging from −8.13 µm (95% confidence interval [CI], −11.12 to −5.13) to 1.58 µm (95% CI, 1.07–2.09) (P < 0.0001 to P < 0.05). Outer retinal clusters displayed thinned paracentral OPL/ONL+HFL, central IS/OS, and peripheral RPE–BM and thickened central RPE–BM, with means ranging from −1.31 µm (95% CI, −2.06 to −0.55) to 2.99 µm (95% CI, 0.97–5.01] (P < 0.0001 to P <0.05). Effect sizes (−2.56 to 9.93 SD), cluster sizes, and eccentricity effects varied. All interlayer correlations were negligible to moderate regardless of AMD severity. Only the RPE–BM was partly thicker with greater AMD severity (up to 5.44 µm; 95% CI, 4.88–6.00; P < 0.01).ConclusionsFrom the early stage, AMD eyes demonstrate thickness differences compared to normal with unique topographies across all retinal layers. Poor interlayer correlations highlight that the outer retina inadequately reflects complete retinal health. The clinical importance of OCT assessment across all individual retinal layers in early/intermediate AMD requires further investigation.

The macular inner plexiform layer thickness as an early diagnostic indicator for Parkinson’s disease

Whether structural alterations of intraretinal layers are indicators for the early diagnosis of Parkinson’s disease (PD) remains unclear. We assessed the retinal layer thickness in different stages of PD and explored whether it can be an early diagnostic indicator for PD. In total, 397 [131, 146, and 120 with Hoehn-Yahr I (H-Y I), H-Y II, and H-Y III stages, respectively] patients with PD and 427 healthy controls (HCs) were enrolled. The peripapillary retinal nerve fiber layer (pRNFL), total macular retinal thickness (MRT), and macular volume (TMV) were measured by high-definition optical coherence tomography, and the macular intraretinal thickness was analyzed by the Iowa Reference Algorithms. As a result, the PD group had a significantly lower average, temporal quadrant pRNFL, MRT, and TMV than the HCs group (all p < 0.001). Moreover, the ganglion cell layer (GCL), inner plexiform layer (IPL), and outer nuclear layer were thinner in patients with PD with H-Y I, and significantly decreased as the H-Y stage increased. In addition, we observed that GCL and IPL thicknesses were both correlated with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS III) scores and non-motor symptoms assessment scores. Furthermore, macular IPL thickness in the superior inner (SI) quadrant (IPL-SI) had the best diagnostic performance in patients with PD with H-Y I versus HCs, with a sensitivity and specificity of 75.06% and 81.67%, respectively. In conclusion, we confirmed the retinal structure was significantly altered in patients with PD in different clinical stages, and that GCL and IPL changes occurred during early PD disease and were correlated with MDS-UPDRS III scores and non-motor symptoms assessment scores. Furthermore, macular IPL-SI thickness might be performed as an early diagnostic indicator for PD.

Retinal nerve fiber layer decrease and choroidal layer increase after four weeks of buprenorphine/naloxone maintenance treatment in opioid use disorder

Background and ObjectivesSpectral-domain optical coherence tomography (SD-OCT) findings in substance use disorders have been investigated in recent years. In this study, we compared the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), and the choroid thickness (CT) of OUD and control groups before and after buprenorphine/naloxone maintenance treatment (BN-MT). MethodsThe OUD group consisted of 46 male subjects and the control group consisted of 49 male subjects. Patients with chronic opioid use and opioid positivity in their urine during the initial SD-OCT application were included in the study. At the end of the fourth week of BN-MT, SD-OCT was repeated and BN positivity was detected in the urine of the patients at this time. ResultsThere was a significant difference between OUD and control groups in terms of nasal superior and CT values of both eyes (p<0.05) before BN use. The values of RNFL sectors and CT of both eyes before and after BN-MT differed significantly (p<0.05); CT increased and RNFL sectors decreased. After BN-MT, psychometric scales differed significantly in favor of the patients (p<0.05). The SD-OCT values of the OUD group after BN-MT were compared with the control group: the right IPL (p=0.003), the left IPL (p=0.023), the right N (p=0.001) and the left N (p<0.001) values were significantly lower in the OUD group. ConclusionThis is the first study to show the SD-OCT findings of patients with OUD before and after BN-MT. The findings of this study may indicate possible effects of chronic opioid use in patients and/or possible effects of exogenous opioid or BN present in the body during SD-OCT applications. However, based on our findings, it is not possible to distinguish between the two possible outcomes. The fact that the use of BN acting through opioid receptors has different effects from exogenous opioids may be due to different receptor profiles.

Interleukin-35 suppresses pyroptosis and protects against neuronal death in retinal ischaemia/reperfusion injury

Retinal ischaemia-reperfusion (I/R) is a pathological process in many eye disorders. Neuroinflammation and cell pyroptosis have been recognized as important in the pathogenesis of tissue damage in retinal I/R. Interleukin (IL)-35 is a novel heterodimeric cytokine that exhibits anti-inflammatory activity in various autoimmune diseases, but its role in retinal I/R and the underlying molecular mechanisms remain unexplored. This research investigated the effect of IL-35 on retinal I/R and the inhibition of pyroptosis and neuronal death. In our study, a murine retinal I/R model was used to explore the neuroprotective effect of recombinant IL-35 protein in vivo. Primary murine microglial cells in pyroptosis and retinal ganglion cells (RGCs) in oxygen and glucose deprivation/reoxygenation (OGD/R) models were employed to assess the antipyroptotic and antiapoptotic effects of IL-35 in vitro. The data showed that IL-35 decreases retinal damage, RGC death, and inner plexiform layer (IPL) thinning in mice with retinal I/R injury, with significant attenuation of pyroptosis in the retina. The study also demonstrated the anti-pyroptotic action of IL-35 in primary microglia stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, primary RGC apoptosis induced by OGD/R was directly suppressed by IL-35, and IL-35-mediated neuroprotection was abrogated when miR-21 was blocked. In conclusion, our results suggest the mechanisms of RGC apoptosis and a new therapeutic target, IL-35, that exerts a robust neuroprotective effect against retinal I/R.

Thicknesses of the retinal layers in patients with Graves' disease with or without orbitopathy.

Graves' orbitopathy (GO) is an inflammatory process that may involve the ocular surface, orbital fat, extraocular muscles, and optic nerves in patients with Graves' disease (GD). We aimed to compare thicknesses of retinal layers in patients with GD with and without GO. One hundred seven patients with GD [23 with GO (Group 1), 84 without GO (Group 2)] and eighteen volunteers (Group 3) were enrolled. The spectral-domain optical coherence tomography (SD-OCT) was used for ophthalmologic evaluation. Seven retinal layers including retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE) were assessed. The thicknesses of layers were compared in groups. The median GCL thickness values in groups 1, 2, and 3 were 14µm, 15µm, and 17.5µm, respectively (p = 0.02). The median IPL thickness was 20µm in group 1, 21µm in group 2, and 22µm in group 3 (p = 0.038). The median RPE thickness values in groups 1, 2, and 3 were 16µm, 17µm, and 18.5µm, respectively (p = 0.001). GCL in group 1 was thinner than in group 3 (p = 0.02), while similar in groups 2 and 3 (p = 0.06). IPL in group 1 was thinner than in group 3 (p = 0.035), while similar in groups 2 and 3 (p = 0.13). RPE in groups 1 and 2 was thinner than in group 3 (p = 0.009, p = 0.001, respectively), while it was similar in groups 1 and 2 (p = 0.93). RNLF, INL, OPL, ONL were similar in all three (p > 0.05 for each). Ganglion cell layer and IPL were thinner in patients with GO than in healthy controls, while both were similar in patients without GO and healthy controls. RPE was thinner in all Graves patients than in healthy controls. Early detection of changes in retinal layers of GD may guide the physician to prevent significant vision problems.

Retinal changes in bipolar disorder as an endophenotype candidate: Comparison of OCT-detected retinal changes in patients, siblings, and healthy controls

Optical coherence tomography (OCT) is a non-invasive imaging technique that detects retinal changes reflecting neurodegeneration. In recent studies in patients with bipolar disorder (BD) abnormal OCT findings have shown. In this study, we aimed to investigate the retinal changes in BD patients and their healthy siblings (HS) by comparing them with the healthy control (HC) group and to explore these findings as potential endophenotype candidates. 31 patients with BD, 31 age-matched HSs and 46 HCs were included and peripapillary retinal nerve fiber layer (RNFL), ganglion cell layer (GCL)+inner plexiform layer (IPL) and macular volume (MV) thicknesses were measured by OCT. The relationship between disease severity parameters, functionality and OCT measurements in the patient group was also investigated. In results, the mean RNFL thicknesses did not differ between groups. All GCL+IPL thicknesses were found to be significantly lower in the patient and sibling groups compared to the HCs. GCL+IPL thicknesses were significantly correlated with functionality of patients and severity of the disorder. Our findings suggest that analysis of retinal layers with OCT may be a beneficial indicator to show neuronal changes in BD and GCL+IPL may be a suitable endophenotype candidate.

Monosodium Glutamate-Induced Mouse Model With Unique Diabetic Retinal Neuropathy Features and Artificial Intelligence Techniques for Quantitative Evaluation.

ObjectiveTo establish an artificial intelligence-based method to quantitatively evaluate subtle pathological changes in retinal nerve cells and synapses in monosodium glutamate (MSG) mice and provide an effective animal model and technique for quantitative evaluation of retinal neurocytopathies.MethodsICR mice were subcutaneously injected with MSG to establish a model of metabolic syndrome. We then established a mouse model of type 1 diabetes, type 2 diabetes, and KKAy mouse model as control. The HE sections of the retina were visualized using an optical microscope. AI technology was used for quantitative evaluation of the retinal lesions in each group of rats. The surface area custom parameters of the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were defined as SR, SIPL, SINL, and SOPL, respectively. Their heights were defined as HR, HIPL, HINL, and HOPL, and the number of ganglion cells was defined as A. Then, the attention-augmented fully convolutional Unet network was used to segment the retinal HE images, and AI technology to identify retinal neurocytopathies quantitatively.ResultsThe attention-augmented fully convolutional Unet network increased PA and IOU parameters for INL, OPL, RNFL, and ganglion cells and was superior in recognizing fine structures. A quantitative AI identification of the height of each layer of the retina showed that the heights of the IPL and INL of the MSG model were significantly less than those of the control groups; the retinas of the other diabetic models did not exhibit this pathological feature. The RNFLs of type 2 diabetes were thinner, and the characteristics of retinopathy were not obvious in the other animal models. The pathological changes seen on HE images were consistent with the results of the quantitative AI evaluation. Immunohistochemistry results showed that NMDAR2A, GluR2, and NRG1 were significantly downregulated in the retina of MSG mice.ConclusionsThe MSG retinopathy model is closely associated with neurotransmitter abnormalities and exhibits important characteristics of retinal neurodegeneration, making it suitable for studying retinal neurocytopathies. The AI recognition technology for retinal images established in the present study can be used for the quantitative and objective evaluation of drug efficacy.

Retinal thinning in progressive supranuclear palsy: differences with healthy controls and correlation with clinical variables

BackgroundAvailable evidence reports conflicting data on retinal thickness in progressive supranuclear palsy (PSP). In studies including healthy controls, PSP showed either the thinning of the retinal nerve fiber layer, macular ganglion cell, inner nuclear, or outer retina layer.ObjectivesThe goals of the present study were to describe retinal layer thickness in a large cohort of PSP compared to healthy controls and in PSP phenotypes using spectral-domain optical coherence tomography (SD-OCT). The additional objective was to verify the relationship between retinal layers thickness and clinical variables in PSP.MethodsUsing a cross-sectional design, we examined retinal structure in 27 PSP patients and 27 controls using standard SD-OCT. Motor and cognitive impairment in PSP was rated with the PSP rating scale and the Montreal Cognitive Assessment battery (MoCA), respectively. Eyes with poor image quality or confounding diseases were excluded. SD-OCT measures of PSP and controls were compared with parametric testing, and correlations between retinal layer thicknesses and disease severity were evaluated.ResultsPSP showed significant thinning of the inner retinal layer (IRL), ganglion cell layer (GCL), inner plexiform layer (IPL), and the outer plexiform layer (OPL) compared to healthy controls. PSP phenotypes showed similar retinal layer thicknesses. Retinal layer thickness correlated with MoCA visuospatial subscore (p < 0.001).ConclusionsWe demonstrated PSP patients disclosed thinner IRL, GCL, IPL, and OPL compared to healthy controls. Furthermore, we found a significant correlation between visuospatial abilities and retinal layers suggesting the existence of a mutual relationship between posterior cognitive function and retinal structure.

Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation.

In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine (AC), and bipolar (BP) cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the striatin-interacting phosphatases and kinases (STRIPAK) complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. AC and BP cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin 3 (Strn3), and both show overlapping functions in RGC survival. Furthermore, loss of Strip1 or Strn3 leads to activation of the proapoptotic marker, Jun, within RGCs, and Jun knockdown rescues RGC survival in strip1 mutants. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.

Hydroxychloroquine treatment alters retinal layers and choroid without apparent toxicity in optical coherence tomography

Background To investigate whether single retinal layer, choroidal and peripapillary retinal fiber layer thicknesses were affected in patients under hydroxychloroquine treatment without retinal toxicityMethods Forty-nine patients under hydroxychloroquine treatment (HCQ group) and 39 healthy volunteers, a total of 88 individuals, were included in the study. Patients with HCQ treatment were further divided into two groups as less than 5 years of HCQ use (group 1, 29 patients) and 5 years or more of HCQ use (group 2, 20 patients). All participants underwent full ophthalmologic examination and optical coherence tomography (OCT) imaging as OCT is a recommended tool for screening toxicity by the American Association of Ophthalmology. The automatic segmentation of retinal layers included retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retina pigment epithelium (RPE), inner retinal layers (IRL), outer retinal layers (ORL) and total retina thickness (TRT). Choroidal thickness (ChT), choroidal vascularity index and peripapillary RNFL were also measured.Results Both inferior and nasal parafoveal RNFL, temporal parafoveal GCL, and IPL layer thicknesses were decreased, while temporal parafoveal RPE layer thicknesses were increased in hydroxychloroquine users. Subfoveal ChTs were significantly reduced in both groups 1 and 2 compared to the control group(p = 0.042 and p = 0.009, respectively) and temporal ChT thicknesses were statistically decreased in group 2 compared to the control group(p = 0.018), but not for nasal ChT.Conclusions Hydroxychloroquine use may cause parafoveal retinal layer thickness alterations and also subfoveal and parafoveal ChT alterations even without evident retinal toxicity in OCT.

Quantitative Optical Coherence Tomography for Longitudinal Monitoring of Postnatal Retinal Development in Developing Mouse Eyes

A better study of postnatal retinal development is essential for the in-depth understanding of the nature of the vision system. To date, quantitative analysis of postnatal retinal development is primarily limited to endpoint histological examination. This study is to validate in vivo optical coherence tomography (OCT) for longitudinal monitoring of postnatal retinal development in developing mouse eyes. OCT images of C57BL/6J mice were recorded from postnatal day (P) 14 to P56. Three-dimensional (3D) frame registration and super averaging were adopted to investigate the fine structure of the retina. Quantitative OCT analysis revealed distinct outer and inner retinal layer changes, corresponding to eye development. At the outer retina, external limiting membrane (ELM) and ellipsoid zone (EZ) band intensities gradually increased with aging, and the IZ band was detectable by P28. At the inner retina, a hyporeflective layer (HRL) between the nerve fiber layer (NFL) and inner plexiform layer (IPL) was observed in developing eyes and gradually disappeared with aging. Further image analysis revealed individual RGCs within the HRL layer of the young mouse retina. However, RGCs were merged with the NFL and the IPL in the aged mouse retina. Moreover, the sub-IPL layer structure was observed to be gradually enhanced with aging. To interpret the observed retinal layer kinetics, a model based on eyeball expansion, cell apoptosis, and retinal structural modification was proposed.

Alteration of EIF2 Signaling, Glycolysis, and Dopamine Secretion in Form-Deprived Myopia in Response to 1% Atropine Treatment: Evidence From Interactive iTRAQ-MS and SWATH-MS Proteomics Using a Guinea Pig Model.

Purpose: Atropine, a non-selective muscarinic antagonist, effectively slows down myopia progression in human adolescents and several animal models. However, the underlying molecular mechanism is unclear. The current study investigated retinal protein changes of form-deprived myopic (FDM) guinea pigs in response to topical administration of 1% atropine gel (10 g/L). Methods: At the first stage, the differentially expressed proteins were screened using fractionated isobaric tags for a relative and absolute quantification (iTRAQ) approach, coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) (n = 24, 48 eyes) using a sample pooling technique. At the second stage, retinal tissues from another cohort with the same treatment (n = 12, 24 eyes) with significant ocular changes were subjected to label-free sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics for orthogonal protein target confirmation. The localization of Alpha-synuclein was verified using immunohistochemistry and confocal imaging. Results: A total of 1,695 proteins (8,875 peptides) were identified with 479 regulated proteins (FC ≥ 1.5 or ≤0.67) found from FDM eyes and atropine-treated eyes receiving 4-weeks drug treatment using iTRAQ-MS proteomics. Combining the iTRAQ-MS and SWATH-MS datasets, a total of 29 confident proteins at 1% FDR were consistently quantified and matched, comprising 12 up-regulated and 17 down-regulated proteins which differed between FDM eyes and atropine treated eyes (iTRAQ: FC ≥ 1.5 or ≤0.67, SWATH: FC ≥ 1.4 or ≤0.71, p-value of ≤0.05). Bioinformatics analysis using IPA and STRING databases of these commonly regulated proteins revealed the involvement of the three commonly significant pathways: EIF2 signaling; glycolysis; and dopamine secretion. Additionally, the most significantly regulated proteins were closely connected to Alpha-synuclein (SNCA). Using immunostaining (n = 3), SNCA was further confirmed in the inner margin of the inner nuclear layer (INL) and spread throughout the inner plexiform layer (IPL) of the retina of guinea pigs. Conclusion: The molecular evidence using next-generation proteomics (NGP) revealed that retinal EIF2 signaling, glycolysis, and dopamine secretion through SNCA are implicated in atropine treatment of myopia in the FDM-induced guinea pig model.

Automated foveal location detection on spectral-domain optical coherence tomography in geographic atrophy patients

PurposeTo develop a fully automated algorithm for accurate detection of fovea location in atrophic age-related macular degeneration (AMD), based on spectral-domain optical coherence tomography (SD-OCT) scans.MethodsImage processing was conducted on a cohort of patients affected by geographic atrophy (GA). SD-OCT images (cube volume) from 55 eyes (51 patients) were extracted and processed with a layer segmentation algorithm to segment Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL). Their en face thickness projection was convolved with a 2D Gaussian filter to find the global maximum, which corresponded to the detected fovea. The detection accuracy was evaluated by computing the distance between manual annotation and predicted location.ResultsThe mean total location error was 0.101±0.145mm; the mean error in horizontal and vertical en face axes was 0.064±0.140mm and 0.063±0.060mm, respectively. The mean error for foveal and extrafoveal retinal pigment epithelium and outer retinal atrophy (RORA) was 0.096±0.070mm and 0.107±0.212mm, respectively. Our method obtained a significantly smaller error than the fovea localization algorithm inbuilt in the OCT device (0.313±0.283mm, p <.001) or a method based on the thinnest central retinal thickness (0.843±1.221, p <.001). Significant outliers are depicted with the reliability score of the method.ConclusionDespite retinal anatomical alterations related to GA, the presented algorithm was able to detect the foveal location on SD-OCT cubes with high reliability. Such an algorithm could be useful for studying structural-functional correlations in atrophic AMD and could have further applications in different retinal pathologies.

In Vivo Sublayer Analysis of Human Retinal Inner Plexiform Layer Obtained by Visible-Light Optical Coherence Tomography

PurposeGrowing evidence suggests that dendrite retraction or degeneration in a subpopulation of the retinal ganglion cells (RGCs) may precede detectable soma abnormalities and RGC death in glaucoma. Visualization of the lamellar structure of the inner plexiform layer (IPL) could advance clinical management and fundamental understanding of glaucoma. We investigated whether visible-light optical coherence tomography (vis-OCT) could detect the difference in the IPL sublayer thicknesses between small cohorts of healthy and glaucomatous subjects.MethodWe imaged nine healthy and five glaucomatous subjects with vis-OCT. Four of the healthy subjects were scanned three times each in two separate visits, and five healthy and five glaucoma subjects were scanned three times during a single visit. IPL sublayers were manually segmented using averaged A-line profiles.ResultsThe mean ages of glaucoma and healthy subjects are 59.6 ± 13.4 and 45.4 ± 14.4 years (P = 0.02.) The visual field mean deviations (MDs) are −26.4 to −7.7 dB in glaucoma patients and −1.6 to 1.1 dB in healthy subjects (P = 0.002). Median coefficients of variation (CVs) of intrasession repeatability for the entire IPL and three sublayers are 3.1%, 5.6%, 6.9%, and 5.6% in healthy subjects and 1.8%, 6.0%, 7.7%, and 6.2% in glaucoma patients, respectively. The mean IPL thicknesses are 36.2 ± 1.5 µm in glaucomatous and 40.1 ± 1.7 µm in healthy eyes (P = 0.003).ConclusionsIPL sublayer analysis revealed that the middle sublayer could be responsible for the majority of IPL thinning in glaucoma. Vis-OCT quantified IPL sublayers with good repeatability in both glaucoma and healthy subjects.

Comparative evaluation of the thickness of macula, ganglion cell layer, and retinal nerve fiber layer in emmetropes, myopes and myopes with lattice degeneration by using Cirrus high-definition optical coherence topography

Purpose: To know the quantitative thickness changes occurring in the macula, retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) of the retina in myopic eyes (ME) and in ME with lattice degeneration (ME-LD) in comparison to emmetropic eyes, with the help of Cirrus HD Optical coherence topography (OCT) 5000 (Carl Zeiss Meditec Inc.). Methods: Hospital-based, nonrandomized prospective study involving 90 eyes, divided into three groups – Group A comprising 30 eyes with − 3–−6D of myopia, Group B comprising 30 eyes with − 3–−6D of myopia with LD and Group C with 30 emmetropic eyes. The central macular thickness (CMT), RNFL, and GCL analysis was done with Cirrus HD OCT 5000 (Carl Zeiss Meditec). Results: The CMT was significantly higher in Group A and B than Group C. There was no significant difference in CMT between Group A and B. Any of the group did not reveal significant difference in parafoveal thickness in any quadrant. Average RNFL, average GCL + inner plexiform layer (IPL), minimum GCL + IPL was significantly thicker in Group C than Group A and B. There was no significant difference between in CMT, average RNFL thickness, average GCL + IPL between Group A and B. Conclusion: There is a significant change in thickness of macula, RNFL, and GCL between emmetropes as compared to myopes and ME-LD but not between myopes and ME-LD. This underscores the need of incorporating a myopic normative database in the present normative built-up of Cirrus OCT. Patients of ME-LD, when being evaluated on different OCT-based parameters, can be considered the same as the myopic population.

Neuroprotection in a glaucoma model by Saffron extract oral supplementation

AbstractPurposeTo study whether saffron extract supplementation can decrease microglial activation signs and reduce retinal ganglion cells (RGCs) loss in a glaucoma model.MethodsAlbino Swiss mice groups; naïve (NG n = 6), saffron naïve (SNG n = 8), laser 3 days (LG3d n = 8), laser 7 days (LG7d n = 6), saffron laser 3 days (SLG3d n = 8) and saffron laser 7 days (SLG7d n = 6). In laser groups, unilateral ocular hypertension (OHT) was induced by OI laser photocoagulation. OHT and contralateral eyes were analysed. Retinal whole‐mounts were processed: (1) Anti Iba‐1 to quantify: Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); Area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ganglion cell layer (NFL‐GCL); Cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; and Arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL. (2) Anti‐P2RY12 for resident microglia. 3) Anti‐Brn3a to quantify Brn3a+ RGCs number.ResultsNo differences were found between naïve groups. LG3d OHT eyes showed significant: increase of Ibacn, Iba‐1 RA and CbIbac and decrease of AAIbac compared to NG. In SLG3d, OHT and contralateral eyes showed a significant reduction of microglial activation signs compared to LG3d. In NG all Iba‐1 + cells were P2RY12+. Compared to NG, in LG3d OHT eyes, the P2RY12 expression was down‐regulated. In SLG3d OHT eyes, saffron extract led to a smaller decrease. In contralateral eyes of LG3d and SLG3d, P2RY12 expression was similar to NG. In LG7d OHT eyes, a significant reduction in the number of Brn3a+ RGCs compared to NG was observed. Saffron extract counteracted this reduction and a significant different were found in SLG7d OHT eyes respect to LG7d OHT eyes. No differences were found between LG7d and SLG7d contralateral eyes.ConclusionsSaffron extract decreases the morphological signs of microglial activation, down‐regulation of P2RY12 and counteract the RCGs loss. Thus, they reduce neuroinflammation associated with IOP increase and protect RGCs.

Reference Database of Inner Retinal Layer Thickness and Thickness Asymmetry in Healthy Thai Adults as Measured by the Spectralis Spectral-Domain Optical Coherence Tomography

Introduction: The study aimed to determine a reference database of the thickness and intraocular thickness asymmetry of total retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in healthy Thai subjects measured by the Spectralis spectral-domain optical coherence tomography. Methods: This cross-sectional study recruited the healthy subjects age ≥18 years, having spherical refraction within ±6 diopters and cylindrical refraction ±3 diopters, from a hospital’s personnel and the people visiting the ophthalmology department. Only 1 eye of each subject was randomly selected for an analysis. Macular images were obtained using posterior pole thickness scan protocol over a 24° × 24° area at the center of the fovea. The automated retinal thickness segmentation values of total retina and three inner retinal layers were calculated for the mean and the mean intraocular thickness difference between superior and inferior retinal hemispheres. The influence of age, gender, and axial length on thickness and thickness asymmetry of individualized retinal layer was evaluated. Results: 252 subjects were included in study with a mean (SD) age of 46.7 (15.8) years, and 120 (47.6%) were males. According to the Early Treatment Diabetic Retinopathy Study map, the inner ring area was the thickest location of the total retina (range; 326.0–341.5 µm), GCL (range; 47.7–52.7 µm), and IPL (range; 39.9–42.1 µm), whereas the thickest location of RNFL was at the outer ring area (range; 18.8–47.5 µm). For posterior pole intraocular thickness asymmetry, the greatest mean ± SD difference was observed for total retina (9.0 ± 2.2 µm), followed by RNFL (9.9 ± 3.2 µm) and GCL (2.7 ± 0.6 µm), and the lowest mean difference was noted for IPL (2.4 ± 0.5 µm). The thickness and thickness asymmetry of each retinal layer were variably influenced by age, gender, and axial length; however, these factors had a minimal influence on the thickness asymmetry maps of GCL and RNFL. Conclusion: The reference database of the macular thickness and thickness asymmetry from this study would be beneficial in determining physiologic variations of the OCT parameters in the healthy Thai population.

Changes in ocular pulse amplitude and posterior ocular structure parameters in type 1 diabetic children without diabetic retinopathy.

Background:It is important to determine changes in posterior ocular structures in the early period before retinopathy develops in pediatric patients with type 1 diabetes mellitus (DM).Objective:To evaluate inner plexiform layer (IPL), ganglion cell layer (GCL), and retinal nerve fiber layer (RNFL) thicknesses, as well as the relationship between choroidal thickness (CT) and ocular pulse amplitude (OPA) in type 1 diabetic children without diabetic retinopathy (DR).Design:A prospective observational study.Methods:Group 1 (n = 44) consisted of pediatric patients with type 1 DM without DR, and Group 2 (n = 65) of pediatric control subjects. Both intraocular pressure (IOP) and OPA were measured using a dynamic contour tonometer. CT, IPL, GCL, and RNFL were all measured using spectral domain optical coherence tomography (OCT).Results:The mean IOP and OPA values were 16.67 ± 2.34 and 1.85 ± 0.34, respectively, in group 1, and 15.14 ± 2.17 and 1.65 ± 0.25 in Group 2 (p = 0.001 for both). The mean subfoveal CT value was 294.30 ± 67.61 μm in group 1 and 394.42 ± 69.65 μm in Group 2 (p < 0.001). The mean GCL and RNFL values were 1.09 ± 0.11 and 96.46 ± 11.69, respectively, in group 1, and 1.14 ± 0.09 and 101.73 ± 9.33 in Group 2 (p = 0.005 and p = 0.008, respectively).Conclusions:IOP and OPA values were higher, and CT, GCL, and RNFL values were lower in children with type 1 DM during the early stages than in the healthy control group. These findings suggest that CT may be a marker of retinal involvement in children with type 1 DM without DR.

Assessment of retinal ganglion-cell complex using spectral-domain optical coherence tomography in diabetic patients without retinopathy

BackgroundDiabetic retinopathy (DR) consists of microvascular changes, although recent investigations have demonstrated that neurodegeneration may occur earlier.ObjectivesTo assess ganglion-cell complex thickness using spectral-domain optical coherence tomography in diabetic patients without retinopathy.Patients and methodsThis was a cross-sectional case–control study conducted at Shebin El kom Ophthalmology Hospital and Tiba Ophthalmological Center on 200 patients divided into two groups: group A involves 100 diabetic patients without DR. Group B involves 100 healthy controls. All participants underwent full ophthalmological and medical history, ophthalmological examination with measurement of the macular ganglion-cell layer–inner-plexiform layer (GCL–IPL) thickness, and retinal nerve-fiber-layer (RNFL) thickness using spectral-domain optical coherence tomography.ResultsMacular GCL–IPL and RNFL thickness were thinner in diabetic patients without retinopathy when compared with healthy controls. The average GCL–IPL was 4.17 μm thinner (95% confidence interval: 1.96–6.38) (P < 0.001) and the average RNFL was 18.65 μm thinner (95% confidence interval: 16.82–20.47) (P < 0.001) in diabetic patients than controls.ConclusionThere was statistically significant thinning in the GCL–IPL and RNFL thickness in the diabetic patient without retinopathy compared with the control group, indicating that diabetes mellitus causes neurodegenerative changes before vascular changes of DR appear.

Characterization of Retinal Architecture in Spinocerebellar Ataxia Type 3 and Correlation with Disease Severity.

Neurodegeneration affects the brain and peripheral nervous system in spinocerebellar ataxia type 3 (SCA3). As the retina is also involved, studying the retinal architecture in a cohort of patients could reveal clinically relevant biomarkers. The aim is to investigate retinal architecture in SCA3 to identify potential biomarkers. We evaluated 38 patients with SCA3 and 25 healthy age-matched controls, who underwent visual acuity assessment, intraocular pressure measurement, and fundoscopy and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We measured the peripapillary retinal nerve fiber layer (pRNFL) thickness in each quadrant of the temporal-superior-nasal-inferior-temporal chart and the macular layer thicknesses in each sector of the inner circle of the Early Treatment Diabetic Retinopathy Study (IC-ETDRS) grid. Linear regression analysis was employed to test the associations between retinal parameters and age, disease duration, CAG repeats, and SARA (Scale of the Assessment and Rating of Ataxia) and ICARS (International Cooperative Ataxia Rating Scale) scores in SCA3. In all sectors, except for the temporal quadrant, pRNFL was significantly thinner in SCA3 patients than in controls. Average total macular, ganglion cell layer (GCL), and inner plexiform layer (IPL) thicknesses were significantly decreased in SCA3 patients in comparison to controls. The average total macular thickness and the average thicknesses of RNFL, GCL, and IPL negatively correlated with ICARS scores, whereas average GCL and IPL thicknesses negatively correlated with SARA scores. The retinal ganglion cells, their dendrites, and axons are selectively affected in SCA3 patients. The RNFL, GCL, and IPL thicknesses in SD-OCT correlate with the clinical phenotype and represent potential biomarkers for future clinical trials and natural history studies. © 2021 International Parkinson and Movement Disorder Society.