Individual Retinal Layers Research Articles

SD-OCT assessment of macular and optic nerve alterations in patients recovered from COVID-19

ObjectiveTo quantify microstructutal alterations in the macula and peripapillary retinal nerve fibre layer (RNFL) in patients recovered from coronavirus disease 2019 (COVID-19) using spectral domain optic coherence tomography (SD-OCT). DesignRetrospective, observational. ParticipantsThis comparative, cross-sectional study included patients who recovered from COVID-19 (Group 1) and age- and sex-matched normal controls (Group 2). MethodsA comprehensive ophthalmic examination, including best-corrected visual acuity and biomicroscopic anterior and posterior segment examination was performed. SD-OCT analysis of the macula and peripapillary RNFL was obtained for each participant. In addition, patient demographics and comorbidities were recorded. Results238 eyes of 122 subjects (Group 1: n = 63; Group 2: n = 59) were included. The incidence of coexisting comorbidity was higher in Group 1 (n = 26/63, 41.3%) compared with Group 2 (n = 12/59, 20.3%) (p = 0.013). The central foveal thickness (CFT) was significantly higher in Group 1 (271.0±26.8 µm) than Group 2 (263.2±22.0 µm) (p = 0.015). The average outer nuclear layer (ONL) thickness at central fovea in Group 1 (85.4±13.3 µm) was significantly thicker than that in Group 2 (81.4±15.2 µm) (p = 0.035). The mean peripapillary RNFL thickness of Group 1 (102.6±8.8 µm) and Group 2 (100.9±8.3 µm) were similar (p = 0.145). The mean choroidal thickness of groups at the fovea and at 1500 µm nasal and temporal to the fovea were not significantly different (p > 0.05 for all). ConclusionSignificant thickness alterations in individual retinal layers and CFT was detected in post–COVID-19 patients. The increase in CFT and ONL thickness might be attributed to direct infection or viral-induced inflammatory response of retina.

Interpretation of anatomic correlates of outer retinal bands in optical coherence tomography.

By providing the sectioning capability to differentiate individual retinal layers, optical coherence tomography (OCT) is revolutionizing eye disease diagnosis and treatment evaluation. A better understanding of the hyper- and hypo-reflective bands in retinal OCT is essential for accurate interpretation of clinical outcomes. In this article, we summarize the interpretations of clinical OCT and adaptive optics (AO) OCT (AO-OCT) of the outer retina in the human eye, and briefly review OCT investigation of the outer retina in animal models. Quantitative analysis of outer retinal OCT bands is compared to established parameters of retinal histology. The literature review and comparative analysis support that both inner/outer segment (IS/OS) junction and IS ellipsoid zone nonexclusively contribute to the second band; and OS, OS tips, and retinal pigment epithelium apical processes contribute to the third band in conventional OCT. In contrast, AO-OCT might predominantly detect the IS/OS junction and OS tip signals at the second and third bands due to its improved sectioning capability and possible AO effect on the sensitivities for recording ballistic and diffusive photons from different regions of the outer retina.

Three "Red Lines" for Pattern Recognition-Based Differential Diagnosis Using Optical Coherence Tomography in Clinical Practice.

Optical coherence tomography (OCT) devices for imaging of the eye are broadly available. The test is noninvasive, rapid, and well-tolerated by patients. This creates a large number of OCT images and patient referrals. Interpretation of OCT findings at the interface between neurological and ophthalmologic conditions has become a key skill in the neuro-ophthalmology service. Similar to the interpretation of visual fields, recogntion of the vertical and horizontal medians are helpful. A third "red line" is added, which will be reviewed here. Levels 1a to 5 evidence. Literature research. There is level 1a evidence that neurodegeneration of the brain is associated with inner retinal layer atrophy. Predominantly, this is driven by retrograde (trans-synaptic) axonal degeneration from the brain to the eye. This process typically stops at the level of the inner nuclear layer (INL). Anterograde (Wallerian) axonal degeneration from the eye to the brain can trespass the INL. The geography of atrophy and swelling of individual macular retinal layers distinguishes prechiasmal from postchiasmal pathology. The emerging patterns are a front-back "red line" at the INL; a vertical "red line" through the macula for chiasmal/postchiasmal pathology; and a horizontal "red line" through the macular for pathology pointing to the optic disc. This is summarized by illustrative case vignettes. The interpretation of patterns of individual retinal layer atrophy (3 "red lines") needs to be combined with recognition of localized layer thickening (edema, structural) at the macula. Certain macular patterns point to pathology at the level of the optic disc. This requires revision of the optic disc OCT and will guide need for further investigations. The 3 "red lines" proposed here may be found useful in clinical practice and the related mnemonics ("half moon," "sunset," "rainbow") for teaching.

Comparison of Anatomical and Functional Results of Surgeries Performed with Nitinol Flex Loop or Forceps in Primary Epiretinal Membrane

ABSTRACT Purpose: To compare surgery’s effect with nitinol flex loop (NFL) or forceps on retinal layers and functional outcomes in the primary epiretinal membrane (ERM). Methods: The operations were classified according to the use of the NFL or forceps. Automatic segmentation of the individual inner retinal layers was performed by spectral-domain optical coherence tomography software, and best-corrected visual acuity (BCVA) before surgery and at the last follow-up visit postoperatively were compared. Results: Forty-two eyes of 42 patients were included with a mean age of 66.9 ± 5.7 years. 45.2% of the surgeries were NFL assisted, 54.8% were forceps assisted. The mean follow-up duration was 9.8 ± 1.3 months. The mean BCVA was 0.79 ± 0.42 vs 0.77 ± 0.39 logMAR in the preoperative period and 0.42 ± 0.27 vs. 0.40 ± 0.21 logMAR at last follow-up in the NFL vs forceps group respectively (p= .403). The retinal nerve fiber layer (RNFL)(32.5% vs. 50.1%, p= .009), ganglion cell layer (18.1% vs. 41.4%, p= .021), inner plexiform layer (13.5% vs. 32.7%, p= .031) and inner nuclear layer (15.5% vs. 30.3%, p= .011) thickness decreased significantly more in the forceps group. The mean surgical time was not significantly different (45.2 ± 5.1 vs. 51.1 ± 6.1 minutes) in the NFL vs. forceps groups, respectively (p= .331). Conclusion: Following primary ERM surgery, the inner retinal layers become thinner; RNFL impacted the most, which was found higher in forceps assisted surgeries. This result shows that the NFL can be used safely in macular surgery.

Assessment of inner retinal oxygen metrics and thickness in a mouse model of inherited retinal degeneration

The retinal degeneration 1 (rd1) mouse is a well-established model of inherited retinal degeneration, displaying photoreceptor degeneration and retinal vasculature damage. The purpose of the current study was to determine alterations in the rate of oxygen delivery from retinal circulation (DO2), the rate of oxygen extraction from the retinal circulation for metabolism (MO2), and oxygen extraction fraction (OEF) in rd1 mice. The study was performed in a total of 18 wild type (WT) and 10 rd1 mice at both 3-weeks and 12-weeks of age. Retinal arterial and venous oxygen contents (O2A and O2V) were measured using phosphorescence lifetime imaging. Total retinal blood flow (TRBF) was determined by fluorescence and red-free imaging. DO2 and MO2 were determined as TRBF × O2A and TRBF × (O2A-O2V), respectively. OEF was calculated as MO2/DO2. The thickness of individual retinal layers was measured from histology sections and inner retina (IR) and total retina (TR) thickness were calculated. TRBF, DO2 and MO2 were lower in rd1 mice compared to WT mice (P ≤ 0.001), whereas OEF was not significantly different between rd1 and WT mice (P = 0.4). TRBF and DO2 were lower at 3-weeks of age compared to 12-weeks of age (P ≤ 0.01), while MO2 was not significantly different between age groups (P = 0.4) and OEF was higher at 3-weeks of age compared to 12-weeks of age (P = 0.003). Additionally, the outer and inner retinal cell layer thicknesses were decreased in rd1 mice at 12-weeks of age compared to both age-matched WT mice and rd1 mice at 3-weeks of age (P ≤ 0.02). MO2 was directly correlated with both IR and TR thickness (R ≥ 0.50; P ≤ 0.03, N = 20). The findings indicate that the rate oxygen is supplied by the retinal circulation is decreased and the reduction in oxygen extracted for metabolism is related to retinal cell layer thinning in rd1 mice.

Evaluation of Automated Segmentation Algorithm for Macular Volumetric Measurements of Eight Individual Retinal Layer Thickness

Background: We evaluated the performance of an automated algorithm available on a clinical OCT (Canon-HS100) for macular volumetric measurements of eight individual retinal layers. Methods and Analysis: Two consecutive three-dimensional scans were acquired on 29 subjects with healthy retinas. Thickness measurements were obtained from eight individual retinal layers in nine macular sectors based on Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. The repeatability was evaluated using the within-subject standard deviation from which the repeatability limits (Rlimit) and coefficient of variation (CoV) were calculated. Results: The repeatability metrics varied among different layers and sectors. The variation among the sectors was larger in two of the outer layers (plexiform and nuclear layer) and the retinal nerve fiber layer. For the other five layers, the repeatability limit was less than 5µm and CoV was less than 7.5% in all nine ETDRS sectors. Conclusions: The repeatability of the OCT-HS100 to measure eight individual retinal layers is good in general. Nevertheless, the repeatability is not homogeneous among different layers and sectors. This needs to be taken into account while designing clinical measurement protocols.

Modelling normal age-related changes in individual retinal layers using location-specific OCT analysis

Current descriptions of retinal thickness across normal age cohorts are mostly limited to global analyses, thus overlooking spatial variation across the retina and limiting spatial analyses of retinal and optic nerve disease. This retrospective cross-sectional study uses location-specific cluster analysis of 8 × 8 macular average grid-wise thicknesses to quantify topographical patterns and rates of normal, age-related changes in all individual retinal layers of 253 eyes of 253 participants across various age cohorts (n = 23–69 eyes per decade). Most retinal layers had concentric spatial cluster patterns except the retinal nerve fibre layer (RNFL) which displayed a nasal, asymmetric radial pattern. Age-related thickness decline mostly occurred after the late 4th decade, described by quadratic regression models. The ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer + Henle’s fibre layer (ONL+HFL) were significantly associated with age (p < 0.0001 to < 0.05), demonstrating similar rates of thickness decline (mean pooled slope = − 0.07 µm/year), while the IS/OS had lesser mean pooled thickness slopes for all clusters (− 0.04 µm/year). The RNFL, OPL, and RPE exhibited no significant age-related thickness change, and the RNFL were significantly associated with sex. Analysis using spatial clusters compared to the ETDRS sectors revealed more extensive spatial definition and less variability in the former method. These spatially defined, clustered normative data and age-correction functions provide an accessible method of retinal thickness analysis with more spatial detail and less variability than the ETDRS sectors, potentially aiding the diagnosis and monitoring of retinal and optic nerve disease.

Effects of different tamponade materials on macular segmentation after retinal detachment repair.

This study used spectral domain-optical coherence tomography (SD-OCT) to evaluate individual retinal layer thickness in eyes with macula-off rhegmatogenous retinal detachment (RRD) treated with silicone oil (SiO) or gas endotamponades. This was a retrospective, interventional, comparative study. The study included 86 eyes of 43 patients who were divided into 3 groups according to endotamponades: SiO, perfluoropropane (C3F8), and sulfur hexafluoride (SF6). The affected eyes were compared with the fellow eyes of the same patient via SD-OCT automated segmentation analysis. Patients with a follow-up of at least 6months were included in the final analysis. Macular segmentation including 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 (ONL), retinal pigment epithelium (RPE), inner retinal layers (IRLs), and outer retinal layers (ORLs) was analyzed. In the SiO group, the mean thickness of each retinal layer including the RNFL, GCL, IPL, ONL, and IRLs within a 1-mm ETDRS subfield of the affected eyes was significantly lower than that of the fellow eyes (P = 0.036, P = 0.028, P = 0.003, P < 0.001, P = 0.013, respectively). There was no significant difference in the C3F8 and SF6 groups (all P > 0.05). The difference between the ONL and IRLs in the SiO-treated eyes differed significantly from that of the gas groups (P = 0.001 and P = 0.045, respectively) The difference in the GCL thickness of the affected eyes and healthy eyes showed a significant correlation with postoperative BCVA changes in the SiO, C3F8, and SF6 groups (P = 0.041, P = 0.048, and P = 0.045, respectively). The findings of our study show that endotamponades used in RRD surgery may have different effects on retinal layers. In addition, SiO may cause undesirable effects on the retinal layers.

Retinal Structural and Microvascular Alterations in Different Acute Ischemic Stroke Subtypes.

Introduction Retinal structural and microvascular damages reflect damage to cerebral microvasculature and neurons. We aimed to investigate neovascular unit abnormalities among patients with large-artery atherosclerosis (LAA) or small-vessel occlusion (SAA) and control subjects. Methods Twenty-eight LAA patients, forty-one SAA patients, and sixty-five age- and gender-matched controls were recruited. Based on optical coherence tomography angiography (OCTA), retinal capillary vessel density was assessed in the general and local sectors, and the thickness of individual retinal layer was extracted from retinal structural images. The differences between structural and microvascular were analyzed. Results The superior peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly different among the three groups, and the LAA group had the thinnest thickness. Compared to the control group, the deep retinal capillary vessel density in other two stroke subgroups were significantly reduced in all regions except in the inferior region (P < 0.05), and the fractal dimension in C2 and C4 regions of deep retina was significantly lower in the LAA group (P < 0.05). Discussion. Compared with superficial microvascular network, deep microvascular network is more sensitive to ischemic stroke. In addition, we have demonstrated quadrant-specific pRNFL abnormalities in LAA and SAA patients. Superior quadrant pRNFL thickness differences between stroke subgroups may suggest that changes in retinal nerve fiber layer are more sensitive to subtype identification than changes in retinal microvascular structure. All in all, the alteration in retinal structural and microvascular may further elucidate the role of the neovascular unit in ischemic stroke, suggesting that the combination of these two indicators could be used for subtype identification to guide prognosis and establish a risk prediction model.

Comparison of Retinal Layer Thicknesses of Highly Myopic Eyes and Normal Eyes

PurposeTo evaluate the differences in individual segmental retinal layer thickness in adult patients with high myopia.MethodsThis study compared the retinal layers of patients with high myopia (axial length of ≥26.0 mm) with those of normal controls using spectral-domain optical coherence tomography. The thicknesses of the retinal layers were compared using nine Early Treatment Diabetic Retinopathy Study subfields. Choroidal thickness was also measured in the subfoveal area.ResultsWe included 37 eyes with high myopia and 37 eyes of healthy subjects. The mean age was 42.95 and 47.73 years (p = 0.114), and the mean axial length was 27.28 and 24.47 mm (p < 0.001), respectively. The parafoveal areas (outer ring segment) of the ganglion cell layer and inner plexiform layer, all segmental areas except the subfoveal region of the inner nuclear layer, most segmental areas (inner superior, inner inferior, outer superior, outer temporal, and outer nasal) of outer plexiform layer, and most segmental areas (subfovea, inner temporal, inner inferior, inner nasal, outer temporal, and outer inferior) of outer nuclear layer were thinner in eyes with high myopia than in normal eyes (all p < 0.05). There were no statistically significant differences between the levels of photoreceptor layer, retinal pigment epithelium, and nerve fiber layer. The mean choroidal thickness was 153.81 ± 64.80 and 239.54 ± 44.28 μm in the high myopia and control groups, respectively, which were significantly different (p < 0.001).ConclusionsIn high myopia without pathologic changes, there was a meaningful thinning of the retina and choroid, especially in most Early Treatment Diabetic Retinopathy Study subfield areas of the deep vascular complex, perifoveal area of the superficial vascular complex, and most areas of the outer nuclear layer in the outer retinal layer, which are associated with myopic axial elongation.

Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms

Individuals with autosomal dominant mutations for Alzheimer disease are valuable in determining biomarkers present prior to the onset of cognitive decline, improving the ability to diagnose Alzheimer disease as early as possible. Optical coherence tomography (OCT) has surfaced as a potential noninvasive technique capable of analyzing central nervous system tissues for biomarkers of Alzheimer disease. To evaluate whether OCT can detect early retinal alterations in carriers of the presenilin 1 (PSEN1 [OMIM 104311]) E280A mutation who are cognitively unimpaired. A cross-sectional imaging study conducted from July 13, 2015, to September 16, 2020, included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired and 10 healthy noncarrier family members, all leveraged from a homogenous Colombian kindred. Statistical analysis was conducted from September 9, 2017, to September 16, 2020. Mixed-effects multiple linear regression was performed to compare the thickness values of the whole retina and individual retinal layers on OCT scans between mutation carriers and noncarriers. Simple linear-effects and mixed-effects multiple linear regression models were used to assess whether age was an effect modifier for PSEN1 mutation of amyloid β levels and retinal thickness, respectively. Fundus photographs were used to compare the number of arterial and venous branch points, arterial and venous tortuosity, and fractal dimension. This study included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired (7 women [70%]; mean [SD] age, 36.3 [8.1] years) and 10 healthy noncarrier family members (7 women [70%]; mean [SD] age, 36.4 [8.2] years). Compared with noncarrier controls, PSEN1 mutation carriers who were cognitively unimpaired had a generalized decrease in thickness of the whole retina as well as individual layers detected on OCT scans, with the inner nuclear layer (outer superior quadrant, β = -3.06; P = .007; outer inferior quadrant, β = -2.60; P = .02), outer plexiform layer (outer superior quadrant, β = -3.44; P = .03), and outer nuclear layer (central quadrant, β = -8.61; P = .03; inner nasal quadrant, β = -8.39; P = .04; inner temporal quadrant, β = -9.39; P = .02) showing the greatest amount of statistically significant thinning. Age was a significant effect modifier for the association between PSEN1 mutation and amyloid β levels in cortical regions (β = 0.03; P = .001) but not for the association between PSEN1 mutation and retinal thickness. No statistical difference was detected in any of the vascular parameters studied. These findings suggest that OCT can detect functional and morphologic changes in the retina of carriers of familial Alzheimer disease who are cognitively unimpaired several years before clinical onset, suggesting that OCT findings and retinal vascular parameters may be biomarkers prior to the onset of cognitive decline.

Spectral-domain OCT changes in retina and optic nerve in children with hypoxic\u2013ischaemic encephalopathy

PurposeTo evaluate the effect of neonatal hypoxic–ischaemic injury on the retina and the optic nerve and to correlate ocular damage with systemic parameters, laboratory tests, neurological imaging and therapeutic hypothermia at birth.MethodsForty-one children with hypoxic–ischaemic encephalopathy (HIE) at birth (9.09 ± 3.78 years) and a control group of 38 healthy subjects (9.57 ± 3.47 years) were enrolled in a cohort study. The HIE population was divided into three subgroups, based on the degree of encephalopathy according to Sarnat score and the treatment with therapeutic hypothermia (TH): Sarnat score I not treated with hypothermia, Sarnat score II-III treated with TH and Sarnat score II-III not subjected to TH. Total macular thickness, individual retinal layers and peripapillary nerve fibre layer thickness were measured with spectral-domain optical coherence tomography. Clinical data of perinatal period of HIE children were collected: APGAR score, pH and base excess of funiculus blood at birth, apnoea duration, brain ultrasound, cerebral MRI ischaemic lesions and blood chemistry tests.ResultsChildren with Sarnat score I did not show a reduction of peripapillary nerve fibres and ganglion cell layer compared to the control group (p = 0.387, p = 0.316). Peripapillary nerve fibre layer was 109.06 ± 7.79 μm in children with Sarnat score II-III treated with TH, 108.31 ± 7.83 μm in subjects with Sarnat score II-III not subjected to TH and 114.27 ± 6.81 μm in the control group (p = 0.028, p = 0.007). Ganglion cell layer was thinner in children with Sarnat score II-III treated with TH (50.31 ± 5.13 μm) compared to the control group (54.04 ± 2.81 μm) (p = 0.01). Inner retinal layers damage correlated with C-reactive protein and lactate dehydrogenase increase, while higher levels of total bilirubin were protective against retinal impairment (p < 0.05). Cerebral oedema was related to peripapillary nerve fibre layer damage (p = 0.046).ConclusionsThickness reduction of inner retinal layer and peripapillary nerve fibre impairment was related to encephalopathy severity. Ocular damage was associated with inflammation and cerebral oedema following hypoxic–ischaemic damage.

Thicknesses of Macular Inner Retinal Layers in Children with Anisometropic Amblyopia.

Objective To investigate the thicknesses of macular inner retinal layers in children with anisometropic amblyopia using spectral domain optical coherence tomography (SD-OCT). Methods Thirty-seven children with anisometropic amblyopia and fifty-seven children with normal vision were recruited in the study. Both eyes of children with anisometropic amblyopia and the right eyes of normal controls underwent scanning with the Spectralis OCT. The segmentation of retinal layers was performed automatically to measure individual inner retinal layers in the five sectors of the macular. An independent sample t-test was applied to compare the mean layer thicknesses of anisometropic eyes and fellow eyes with those of control eyes. Results There was no significant difference in the total macular thickness between amblyopic and control eyes. However, in the peripheral macular area, three of the four quadrants of both the ganglion cell layer (GCL) and the inner plexiform layer (IPL) thicknesses were significantly reduced in amblyopic eyes compared to control eyes. Moreover, two of the four quadrants of the GCL thickness and three of the four quadrants of the IPL thickness in the peripheral macular area were significantly reduced in fellow eyes than in control eyes. Conclusion The SD-OCT data revealed differences in the thicknesses of some macular inner retinal layers in both eyes of children with anisometropic amblyopia compared with those with emmetropia, indicating that structural changes might exist in the retina of children with amblyopia.

Longitudinal retinal layer changes in preclinical Alzheimer's disease.

PurposeSeveral studies found reduced retinal thickness on optical coherence tomography (OCT) in Alzheimer’s disease (AD), even in preclinical stages, labelling this technique of interest as biomarker. In this study, we examine retinal thickness changes in preclinical AD, as defined by cognitively normal individuals with amyloid‐beta (Aβ) on positron emission tomography (PET).MethodsFor this monocentre study, 145 cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the EMIF‐AD PreclinAD study. At baseline, participants underwent [18F] flutemetamol PET that was visually rated for cortical Aβ. Binding potential was calculated as continuous measure for Aβ. Optical coherence tomography (OCT) was performed at baseline and after 22 months to assess changes in total and individual inner retinal layer thickness in the macular region (ETDRS circles) and peripapillary retinal nerve fibre layer thickness. Differences in rate of change between amyloid‐beta positive and negative individuals and associations between binding potential and change in retinal thickness were evaluated.ResultsSixteen participants (11%) were positive for Aβ. Change in retinal thickness did not differ in any region between Aβ+ and Aβ− individuals. A positive association between binding potential and change in inner plexiform layer thickness was observed in the inner macular ring (beta = 1.708, CI = 0.575 to 2.841, p = 0.003).ConclusionAβ+ individuals did not differ in rate of change of any retinal layer compared to controls, but higher binding potential at baseline was associated with less IPL thinning over time. Optical coherence tomography (OCT) as a longitudinal screening tool for preclinical AD seems limited, but IPL changes offer leads for further research.

Density-based classification in diabetic retinopathy through thickness of retinal layers from optical coherence tomography

Diabetic retinopathy (DR) is a severe retinal disorder that can lead to vision loss, however, its underlying mechanism has not been fully understood. Previous studies have taken advantage of Optical Coherence Tomography (OCT) and shown that the thickness of individual retinal layers are affected in patients with DR. However, most studies analyzed the thickness by calculating summary statistics from retinal thickness maps of the macula region. This study aims to apply a density function-based statistical framework to the thickness data obtained through OCT, and to compare the predictive power of various retinal layers to assess the severity of DR. We used a prototype data set of 107 subjects which are comprised of 38 non-proliferative DR (NPDR), 28 without DR (NoDR), and 41 controls. Based on the thickness profiles, we constructed novel features which capture the variation in the distribution of the pixel-wise retinal layer thicknesses from OCT. We quantified the predictive power of each of the retinal layers to distinguish between all three pairwise comparisons of the severity in DR (NoDR vs NPDR, controls vs NPDR, and controls vs NoDR). When applied to this preliminary DR data set, our density-based method demonstrated better predictive results compared with simple summary statistics. Furthermore, our results indicate considerable differences in retinal layer structuring based on the severity of DR. We found that: (a) the outer plexiform layer is the most discriminative layer for classifying NoDR vs NPDR; (b) the outer plexiform, inner nuclear and ganglion cell layers are the strongest biomarkers for discriminating controls from NPDR; and (c) the inner nuclear layer distinguishes best between controls and NoDR.

OCT Angiographic Findings in Retinal Angiomatous Proliferation.

OCT angiography (OCT-A) allows non-invasive blood flow registration of the retina and choroid. In contrast to fluorescein angiography (FA), no dye has to be administered. The OCT-A also provides depth-selective information. OCT-A and FA were compared in patients with neovascular age-related macular degeneration (AMD) with retinal angiomatous proliferation (RAP) stage 1. In stage 1, the neovascularizations are intraretinal. In contrast to the two-dimensional total image of the FA, the OCT-A allows a depth-selective display of the individual retinal layers. In this way, a conclusion can be drawn about the place of origin of the RAP. Three patients with neovascular AMD and RAP stage 1 were included. They were examined with OCT (ZEISS CIRRUS HD-OCT 5000, Carl Zeiss Meditec, Inc., Dublin, USA), OCT-A (ZEISS AngioPlex OCT-Angiography) as well as FA (HRA2, Heidelberg Engineering) between January 2016 and March 2019. A complete ophthalmological examination was performed. A qualitative analysis of the OCT-A images (3 × 3 and 6 × 6 mm) and the FA images was carried out. Leaks in the FA were compared with the en-face images of the OCT-A followed by a depth-selective assignment using the corresponding B-scans of the OCT-A. It was one woman and two men aged 66 - 89 years. The visual acuity was 0.4 in the first, 0.5 p in the second and 0.8 in the third patient. The diagnosis of RAP stage 1 could be made both in the OCT, the FA and the OCT-A. All patients showed macular edema in the OCT. The FA showed selective hyperfluorescence in the early phase and fluorescein extravasation in the late phase. In OCT-A, the blood flow in all patients could be shown in the hyperreflective structure of the RAP in the B-scan. The first patient showed two RAP lesions in the FA, which were in the deep vascular plexus in the OCT-A. In the second patient, three RAP lesions were found in the FA, and a total of five RAP lesions in the OCT-A. One could be located in the superficial and deep vascular plexus, four in the deep vascular plexus. The third patient showed one RAP lesion in the FA as well as in the OCT-A, which could be assigned to the superficial vascular plexus. The OCT-A is well suited for the diagnosis of RAP stage 1. In the present cases, the diagnosis in the OCT-A could be made as clearly as by FA. A major advantage of the OCT-A results from the non-invasive character and the depth selectivity. The RAP 1 lesions could be assigned to both the superficial and the deep vascular plexus. Depth selection is not possible with the FA due to the summary picture.

Association between individual retinal layer thickness and visual acuity in patients with epiretinal membrane: a pilot study.

PurposeWe investigated the correlation between visual acuity (VA) and individual retinal layer thickness in the foveal, parafoveal, and perifoveal regions of patients with an idiopathic epiretinal membrane (ERM).MethodsOne hundred and five subjects presenting with unilateral idiopathic ERM were included in this study. We segmented each patient’s optical coherence tomography (OCT) image into seven layers and calculated the mean layer thickness in the foveal, parafoveal, and perifoveal regions using the Iowa Reference Algorithm. In 105 patients with ERM, we detected correlations between their macular regions’ individual retinal layer thickness and their best corrected VA. Thirty-one of the 105 patients with ERM underwent vitrectomy and completed six months of follow-up. We then compared the 31 surgical patients’ preoperative and postoperative individual retinal layer thickness in each macular region. Additionally, the association between preoperative individual retinal layer thickness in each macular region and VA six months post-surgery in patients with ≥ two Snellen lines of visual improvement was determined.ResultsMultiple linear regression analysis showed that the inner nuclear layer (INL) thickness in the foveal, parafoveal, and perifoveal region were all associated with VA in the 105 patients (R2 = 0.344, P < 0.001; R2 = 0.427, P < 0.001; and R2 = 0.340, P < 0.001, respectively). Thirty-one surgical patients 6 months post-surgery showed significantly decreased thicknesses (P ≤ 0.012) of the foveal INL, inner plexiform layer (IPL), and outer nuclear layer (ONL); the parafoveal retina nerve fiber layer (RNFL), IPL, INL, and ONL; and the perifoveal RNFL, IPL, INL, ganglion cell layer (GCL), outer plexiform layer (OPL), and photoreceptor layer (PRL). We found a weak correlation between postoperative VA and preoperative foveal and perifoveal RNFL thickness (r = 0.404 and r = 0.359, respectively), and a moderate correlation between postoperative VA and preoperative foveal and parafoveal INL thickness (r = 0.529 and r = 0.583, respectively) in the 31 surgical patients (P ≤ 0.047). The preoperative INL thickness in the foveal, parafoveal, and perifoveal regions showed a moderate to strong correlation (r = 0.507, 0.644, and 0.548, respectively), with postoperative VA in patients with ≥ 2 lines of visual improvement (P ≤ 0.038).ConclusionWe detected a correlation between retinal damage and VA in the parafoveal, perifoveal, and foveal regions. Our results suggest that INL thickness in all macular regions may be a prognostic factor for postoperative VA in ERM patients.

Structural imaging of the retina in psychosis spectrum disorders: current status and perspectives.

Structural changes of the retina in schizophrenia and other psychotic disorders seem plausible as these conditions are accompanied by widespread morphological abnormalities of the brain. Advances in structural retinal imaging have led to the possibility of precise quantification of individual retinal layers, using optical coherence tomography (OCT) scanners. The aggregation of information related to OCT findings in schizophrenia has resulted in three metaanalyses, which are currently described. Areas where retinal changes were reported include retinal nerve fiber layer (RNFL), ganglion cell layer complex (GCC), macular volume, and macular thickness, but findings on affected retinal segments vary to some extent across studies. Discrepancies in individual studies could be because of small samples, heterogeneity within schizophrenia (phase of the illness, illness duration, predominant symptomatology), inconsistent reporting of antipsychotic therapy, insufficient control of confounding variables (somatic comorbidities, smoking, and so on), and use of the different types of OCT scanners. Exploration of potential disturbances in retinal architecture could provide new insights into neuronal changes associated with psychosis spectrum disorders, with potential to elucidate the nature and timing of developmental, progressive, inflammatory, and degenerative aspects of neuropathology and pathophysiology, and to assist with characterizing heterogeneity and facilitating personalized treatment approaches.

Evaluation of retinal vessel quantity within individual retinal structural layers using optical coherence tomography angiography.

To evaluate retinal vessel quantity within various retinal structural layers using optical coherence tomography angiography (OCTA). In this IRB-approved study, 22 normal eyes (from 22 subjects) were imaged using the Spectralis OCT2, with a 15 × 15 degree OCTA scan centered on fovea and two additional 15 × 5 degree OCTA scans, displaced temporally and nasally by 15 degrees along the fovea-Bruch's membrane opening (BMO) axis. Following projection artifact removal (PAR), vessel quantity (i.e., amount of flow signal) within each retinal nuclear and plexiform layer was assessed across the scan and was plotted as a vessel quantity profile over this fovea-BMO axis. Vessel quantity was correlated against the retinal layer thickness at the corresponding locations using the Spearman correlation. For the nerve fiber layer (NFL), the vessel quantity was highest nasally and declined towards the fovea and was near zero temporal to the fovea with or without PAR. For all other retinal layers, the retinal vessel quantities were greatest in the parafoveal retina, peaking approximately 5 degrees from the foveal center. Before PAR, the parafoveal vessel quantity was highest in the inner plexiform layer (IPL). Following PAR, the vessel quantity in the IPL decreased but was relatively unchanged in the other layers. The vessel quantity correlated moderately well with retinal layer thickness (r = 0.432 to 0.511; P < 0.05 among the various layers). Retinal vessel quantity varies significantly among the various structural layers, with significant regional variability. Projection artifact can significantly impact retinal vessel quantity in the deeper layers, but the effect appears to be most pronounced in the IPL.

Optical Coherence Tomography Angiography in Diabetes and Diabetic Retinopathy.

Diabetic retinopathy (DR) is a common complication of diabetes mellitus that disrupts the retinal microvasculature and is a leading cause of vision loss globally. Recently, optical coherence tomography angiography (OCTA) has been developed to image the retinal microvasculature, by generating 3-dimensional images based on the motion contrast of circulating blood cells. OCTA offers numerous benefits over traditional fluorescein angiography in visualizing the retinal vasculature in that it is non-invasive and safer; while its depth-resolved ability makes it possible to visualize the finer capillaries of the retinal capillary plexuses and choriocapillaris. High-quality OCTA images have also enabled the visualization of features associated with DR, including microaneurysms and neovascularization and the quantification of alterations in retinal capillary and choriocapillaris, thereby suggesting a promising role for OCTA as an objective technology for accurate DR classification. Of interest is the potential of OCTA to examine the effect of DR on individual retinal layers, and to detect DR even before it is clinically detectable on fundus examination. We will focus the review on the clinical applicability of OCTA derived quantitative metrics that appear to be clinically relevant to the diagnosis, classification, and management of patients with diabetes or DR. Future studies with longitudinal design of multiethnic multicenter populations, as well as the inclusion of pertinent systemic information that may affect vascular changes, will improve our understanding on the benefit of OCTA biomarkers in the detection and progression of DR.