Inner Retinal Layer Thickness Research Articles

Comparative analysis of changes in retinal layer thickness following femtosecond laser-assisted cataract surgery and conventional cataract surgery

BackgroundTo investigate the influence of femtosecond laser-assisted cataract surgery (FLACS) on macula by examining changes in retinal layers after FLACS and to compare these changes with those after conventional cataract surgery (CCS).MethodsThis study included 113 unrelated Korean patients with age-related cataract who underwent CCS or FLACS in Severance Hospital between September 2019 and July 2021. Optical coherence tomography was performed before and 1 month after surgery. The total retinal layer (TRL) was separated into the inner retinal layer (IRL) and outer retinal layer (ORL); moreover, the IRL was subdivided into the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, and outer nuclear layer. We performed between-group comparisons of the postoperative thickness in each retinal layer and the postoperative differences in retinal thickness. The average retinal thickness of the four inner macular ring quadrants was used for comparative analysis.ResultsCompared with the CCS group, the FLACS group exhibited a thicker ORL (P = 0.004) and a thinner INL (P = 0.007) after surgery. All retinal layer thickness values showed significant postoperative changes regardless of the type of surgery (P < 0.05). The postoperative increase in TRL and IRL thickness was significantly smaller in the FLACS group than in the CCS group (P = 0.027, P = 0.012).ConclusionsThe 1-month postoperative retinal changes were less pronounced in the FLACS group than in the CCS group.

Lower thickness of inner retinal layers is associated with an increased risk of incident dementia and Alzheimer’s disease – an individual participant data analysis of four prospective cohort studies (69,955 participants)

AbstractBackgroundRetinal imaging tools may be biomarkers for the early identification of individuals at risk for dementia. Currently, it remains unclear whether retinal neurodegeneration precedes the onset of clinical dementia as few prospective data have been published. The objective To investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all‐cause dementia and Alzheimer’s disease.MethodWe performed an individual participant data meta‐analysis using data from four prospective cohort studies with a total of 69,955 participants (n = 1,087 cases of incident all‐cause dementia; n = 520 cases incident Alzheimer’s disease; follow‐up time median [interquartile range; IQR] 11.3 [8.8 ‐ 11.5] years). We investigated the associations of baseline macular retinal nerve fiber layer (mRNFL) thickness and ganglion cell‐inner plexiform layer (mGCIPL) thickness (expressed per standard deviation lower thickness) with incident dementia. We used Cox proportional hazards models adjusted for age, sex, educational level, and other key dementia risk factors. Missing data for covariables were imputed. We tested for interaction with age, sex, apolipoprotein E (APOE) genotype status, and educational level.ResultAfter adjustment for age, sex, educational level, and key dementia risk factors, lower baseline mRNFL thickness was significantly associated with higher incidence of all‐cause dementia and Alzheimer’s disease (per SD lower mRNFL thickness, hazard risk [95% confidence interval], 1.10 [1.02; 1.17] and 1.11 [1.001; 1.23], respectively); and lower mGCIPL thickness was not significantly associated with these outcomes (per SD lower mGCIPL thickness, 1.04 [0.99; 1.10] and 1.01 [0.94; 1.09], respectively). Age, sex, apolipoprotein E (APOE) genotype status, and educational level did not (consistently) modify these associations.ConclusionThis individual participant data meta‐analysis found that lower baseline thickness of inner retinal layers was associated with up to approximately 10% higher risk of incident all‐cause dementia and Alzheimer’s disease. These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia and that retinal imaging tools may be biomarkers for the early identification of individuals at risk for dementia.

Lower thickness of inner retinal layers is associated with an increased risk of incident dementia and Alzheimer’s disease – an individual participant data analysis of four prospective cohort studies (69,955 participants)

AbstractBackgroundRetinal imaging tools may be biomarkers for the early identification of individuals at risk for dementia. Currently, it remains unclear whether retinal neurodegeneration precedes the onset of clinical dementia as few prospective data have been published. The objective To investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all‐cause dementia and Alzheimer’s disease.MethodWe performed an individual participant data meta‐analysis using data from four prospective cohort studies with a total of 69,955 participants (n = 1,087 cases of incident all‐cause dementia; n = 520 cases incident Alzheimer’s disease; follow‐up time median [interquartile range; IQR] 11.3 [8.8 ‐ 11.5] years). We investigated the associations of baseline macular retinal nerve fiber layer (mRNFL) thickness and ganglion cell‐inner plexiform layer (mGCIPL) thickness (expressed per standard deviation lower thickness) with incident dementia. We used Cox proportional hazards models adjusted for age, sex, educational level, and other key dementia risk factors. Missing data for covariables were imputed. We tested for interaction with age, sex, apolipoprotein E (APOE) genotype status, and educational level.ResultAfter adjustment for age, sex, educational level, and key dementia risk factors, lower baseline mRNFL thickness was significantly associated with higher incidence of all‐cause dementia and Alzheimer’s disease (per SD lower mRNFL thickness, hazard risk [95% confidence interval], 1.10 [1.02; 1.17] and 1.11 [1.001; 1.23], respectively); and lower mGCIPL thickness was not significantly associated with these outcomes (per SD lower mGCIPL thickness, 1.04 [0.99; 1.10] and 1.01 [0.94; 1.09], respectively). Age, sex, apolipoprotein E (APOE) genotype status, and educational level did not (consistently) modify these associations.ConclusionThis individual participant data meta‐analysis found that lower baseline thickness of inner retinal layers was associated with up to approximately 10% higher risk of incident all‐cause dementia and Alzheimer’s disease. These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia and that retinal imaging tools may be biomarkers for the early identification of individuals at risk for dementia.

Determining relative thickness of inner retinal layers on single-line foveal optical coherence tomography (OCT) in healthy pediatric eyes—normative data for handheld OCT

Handheld optical coherence tomography (HH-OCT) lacks integrated segmentation/analysis software. Optic neuropathies cause ganglion cell layer (GCL) thinning, with normal to thickened inner nuclear layer (INL), suggesting the potential value of estimating the GCL/INL ratio on single-line foveal HH-OCT scans. This study determines this ratio in macular scans from healthy eyes of young children using HH-OCT and overhead-mounted OCT. Macular OCT scans were obtained using either HH-OCT or overhead-mounted Spectralis FLEX-OCT in children ages 0-5 years undergoing clinically indicated anesthesia/sedation. Exclusion criteria included gestational age <37 weeks, neurologic disease, amblyopia, ocular disease, or large refractive error (spherical equivalent beyond -3.00 D to +8.00 D). For HH-OCT, the GCL and INL were manually measured in pixels from single-line macular scans at the thickest point nasal and temporal to the fovea. For FLEX-OCT images, measurements were aided by automated software. HH-OCT was obtained on 38 eyes (38 children, mean age 2.4 ± 1.8 years) and FLEX-OCT on 56 eyes (56 children, mean age 2.3 ± 1.5 years). Mean nasal GCL/INL was 1.24 ± 0.18 (min/max = 0.92/1.75) for HH-OCT and 1.29 ± 0.18 (min/max = 0.96/1.66) for FLEX-OCT (P = 0.11). Mean temporal GCL/INL was 1.22 ± 0.24 (min/max = 0.66/1.70) for HH-OCT and 1.19 ± 0.16 (min/max = 0.86/1.47) for FLEX-OCT (P = 0.47). Mean normative GCL/INL ratios were approximately 1.2 at the thickest macular areas both nasal and temporal to the fovea, with either HH-OCT or FLEX-OCT in young children's eyes. These values may prove useful when HH-OCT is used to assess optic neuropathies, in which the GCL/INL ratio is expected to be decreased.

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies.

Our main objectivewas to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n=1087 cases of incident all-cause dementia; n=520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Assessment of the impact of an early acute immune challenge on the diabetic retina

AbstractPurpose: Diabetic retinopathy (DR) is a leading cause of blindness worldwide. It has been claimed that infections may enhance the progression of retinal degenerative diseases to more severe stages. Infections prime microglia, the immune cells of central nervous system. Microglia‐mediated neuroinflammation is a hallmark of DR. We hypothesized that an infection at adolescence negatively impacts on the retina later in life when it is challenged with diabetes.Methods: An infection was mimicked by an intraperitoneal injection of lipopolysaccharide (LPS), in Wistar rats. Diabetes was induced by streptozotocin. Retinal function was assessed by electroretinography and retinal structure was evaluated by optical coherence tomography (OCT). Microglia reactivity was assessed by immunolabelling Iba‐1 and MHC‐II.Results: We evaluated first the impact of LPS per se on the retina. Scotopic threshold response, indicative of retinal ganglion cell function, presented a significant decreased amplitude 30 days after LPS injection, without alterations in the function of other retinal neurons. OCT revealed that 1 day after LPS there was an increase in the thickness of inner retinal layers. Eye fundus images showed a thickening of retinal vessels and the presence of vitreous infiltrates, 1 and 5 days after LPS injection. LPS also significantly increased microglial reactivity 1 day after the injection. Then, we evaluated the impact of LPS when the retina was also exposed to a diabetic insult (30 days). In diabetic animals previously exposed to LPS, there was a decrease in the amplitude of cone response, evaluated by flicker (first and second harmonic).Conclusions: LPS per se affects the retina in several parameters, mainly in the first days upon LPS challenge. Moreover, LPS priming negatively impacts on cone cell function upon diabetes.Supported by FCT, Portugal (PEst UIDB/04539/2020 and UIDP/04539/2020) and Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BrainHealth 2020).

Inner retinal layers' thickness changes in relation to age in healthy eyes

AbstractPurpose: Characterizing the structural change of the macula produced by aging in healthy eyes is essential to discriminate physiological alterations typical of aging from other pathological signs. In this study, macular thicknesses measured by spectral‐domain optical coherence tomography (SD‐OCT) were characterized in young, middle‐aged, and older subjects without ocular pathology.Methods: The study design was observational cross‐sectional and was conducted in 154 eyes of 154 healthy participants between 20 and 80 years (mean 44 ± 18 years of age) divided into three age groups: young (20–39), middle‐aged (40–59) and older (60–80). Macular thicknesses were measured through SD‐OCT using the grid employed of the Early Treatment Diagnostic Retinopathy Study (ETDRS). We analysed five sub‐fields: the central fovea and the four regions (temporal, nasal, superior, inferior) of the parafoveal ring. Mean macular thicknesses were recorded for each of the three retinal segmentations: the inner retinal layer (IRL), the outer retinal layer (ORL) and the total retinal layer. Comparisons of macular thicknesses across age groups were performed.Results: Mean total and ORL thicknesses were not significantly different in the central subfield and each region of the parafoveal ring of the ETDRS grid (temporal, nasal, nasal, inferior and overall) for the three age groups. However, age had a significant effect on IRL thickness in each region of the parafoveal ring. In the superior, nasal and inferior regions, mean IRL thicknesses decreased significantly in the older age group compared to the other age groups (all p &lt; 0.0001). In the temporal region, mean IRL thickness decreased with age and was significantly different for each of the three age groups (p &lt; 0.0001).Conclusions: Age did not significantly influence total and ORL thicknesses in the macula. However, the macular thickness of the IRL decreased in subjects older than 60 years of age.

Speckle Contrast as Retinal Tissue Integrity Biomarker in Patients with Type 1 Diabetes Mellitus with No Retinopathy

To study the retinal and choroidal layers in type 1 diabetes mellitus (DM1) without diabetic retinopathy (DR), using speckle contrast of optical coherence tomography (OCT) images as a tissue biomarker in comparison with healthy subjects. OCT Spectralis images of 148 eyes, 84 from DM1 patients without DR signs, and 64 belonging to the control group, were collected. The speckle contrast and thickness of the inner retinal layer (IRL), the outer retinal layer (ORL), and the choroidal layer in the nasal parafoveal area (N3), were prospectively analyzed. A statistically significant difference (p = 0.001) in the IRL thickness between groups was observed, being thicker in the DM1 group. There were no differences in the ORL and choroidal thicknesses between groups. A statistically significant difference (p = 0.02) in the IRL speckle contrast was obtained, being lower in the DM1 group. The maximum speckle contrast was reached in the ORL for both groups, although in the DM1 group, it occurs closer to the choroid, at 64 ± 8 μm (p = 0.008). Statistically significant differences were found in speckle contrast and thickness between the control and the DM1 group, suggesting an IRL alteration of DM1 patients, supporting the retinal neurodegeneration before DR signs are observed.

Morphology of foveal hypoplasia: Hyporeflective zones in the Henle fiber layer of eyes with high-grade foveal hypoplasia.

Foveal hypoplasia is characterized by the persistance of inner retinal layers at the macular center. We evaluated using spectral-domain optical coherence tomography (SD-OCT) morphological parameters of the macular center of eyes with foveal hypoplasia and describe the presence of hyporeflective zones in the Henle fiber layer (HFL) of eyes with high-grade foveal hypoplasia. Eyes with foveal hypoplasia were classified into two groups: high-grade foveal hypoplasia with thick inner retinal layers at the macular center (thickness above 100 μm; 16 eyes of 9 subjects) and low-grade foveal hypoplasia with thinner inner retinal layers at the macular center (thickness below 100 μm; 25 eyes of 13 subjects). As comparison, SD-OCT images of normal control eyes (n = 75) were investigated. Eyes with foveal hypoplasia displayed shorter central photoreceptor outer segments (POS), a thinner central myoid zone, and a thicker central HFL compared to control eyes. Eyes with high-grade foveal hypoplasia also displayed a thinner central outer nuclear layer (ONL) compared to eyes with low-grade foveal hypoplasia and control eyes. There was a negative correlation between the thicknesses of the central ONL and HFL in eyes with foveal hypoplasia; however, the total thickness of both ONL and HFL was similar in all eye populations investigated. Visual acuity of subjects with foveal hypoplasia was negatively correlated to the thickness of the central inner retinal layers and positively correlated to the length of central POS. In contrast to central POS, the length of paracentral POS (0.5 and 1.0 mm nasal from the macular center) was not different between the three eye populations investigated. The paracentral ONL was thickest in eyes with high-grade foveal hypoplasia and thinnest in control eyes. Hyporeflective zones in the HFL were observed on SD-OCT images of eyes with high-grade foveal hypoplasia, but not of eyes with low-grade foveal hypoplasia and control eyes. OCT angiography images recorded at the level of the HFL of eyes with high-grade foveal hypoplasia showed concentric rings of different reflectivity around the macular center; such rings were not observed on images of eyes with low-grade foveal hypoplasia and control eyes. It is suggested that the hyporeflective zones in the HFL of eyes with high-grade foveal hypoplasia represent cystoid spaces which are surrounded by Henle fiber bundles. Cystoid spaces are likely formed because there are fewer Henle fibers and a thinner central ONL despite an unchanged thickness of both ONL and HFL. Cystoid spaces may cause the concentric rings of different reflectivity around the macular center in the HFL of eyes with high-grade foveal hypoplasia.

Abnormal foveal morphology in carriers of oculocutaneous albinism

Background/aimsTo investigate the foveal morphology in carriers of oculocutaneous albinism (OCA) using spectral domain optical coherence tomography (SD-OCT). A cross-sectional, observational study.MethodsHandheld SD-OCT (Envisu C2300) was used to acquire horizontal...

Correlation between foveal microvasculature and inner retinal layer thickness in type 2 diabetes: an optical coherence tomography angiography study

Aim The aim of this study was to evaluate the correlation between foveal microvasculature and inner retinal layer (IRL) thinning in patients with type 2 diabetes using optical coherence tomography angiography (OCTA).Patients and methods This is a prospective comparative study that included 100 eyes of 100 subjects: 50 eyes of diabetic patients with type 2 diabetes having mild to moderate nonproliferative diabetic retinopathy (NPDR) and 50 eyes of normal subjects. Foveal avascular zone (FAZ) area and vessel density of parafoveal and perifoveal areas were calculated using OCTA. The IRL thickness was measured using optical coherence tomography (OCT). The correlation between the IRL thickness and both FAZ area and macular vessel density was measured.Results The mean FAZ area was significantly larger in the NPDR group (0.69±0.01 mm2) than in the normal eyes group (0.45±0.02 mm2), (P=0.01). The mean parafoveal and perifoveal vessel density in the superficial capillary layer were significantly decreased in eyes with NPDR (46.7±6.5% and 43.8±7.1%, respectively) than in normal eyes (69.5±4.2% and 66.2±4.3%, respectively) (P=0.001). The mean parafoveal and perifoveal vessel density in the deep capillary layer had significantly lower values in eyes with NPDR (51.3±2.3% and 49.5±4.2%, respectively) than in normal eyes (70.1±5.4% and 68.3±3.73%, respectively), (P=0.001). The mean IRL thickness was significantly less in the NPDR eyes (54.7±6.8 μm) than in normal eyes (79.3±6.9 μm), (P=0.001). A statistically significant correlation was found between the IRL thickness and both FAZ area and macular vessel density in eyes with NPDR (P<0.001).Conclusion OCTA revealed that foveal microcirculatory alterations (FAZ area and macular vessel density) in diabetic eyes were related to the IRL thickness.

Optical coherence tomography in multiple sclerosis: A 3-year prospective multicenter study.

ObjectiveTo evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing‐remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS).MethodsIndividuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6‐monthly thereafter).ResultsOCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS‐associated optic neuritis––group differences (95% CI) over 3 years: pRNFL: −1.86 (−2.54, −1.17) µm; mGCIPL: −2.03 (−2.78, −1.28) µm (both p < 0.0001; effect sizes 0.39 and 0.34). Greater inner retinal layer atrophy was observed in individuals diagnosed with RRMS <3 years versus >5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy (p < 0.0001). There was no correlation of OCT data with disability progression.InterpretationOCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.

Changes in retinal layers in type 1 diabetes mellitus without retinopathy measured by spectral domain and swept source OCTs

To evaluate changes in inner retinal layer (IRL) thicknesses in patients with type 1 diabetes mellitus (DM1) with no diabetic retinopathy (DR) using two different optical coherence tomography (OCT) devices. Ninety DM1 and 60 healthy eyes were evaluated using spectral domain (SD)-OCT and swept source (SS)-OCT to measure changes in the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and inner nuclear layer (INL) thicknesses in all Early Treatment of Diabetic Retinopathy Study (ETDRS) macular areas. Functional tests were performed in both groups, including ETDRS with 100, 2.5 and 1.25% contrast, and color vision. The mean ages were 42.93 ± 13.62 and 41.52 ± 13.05 years in the diabetic and control groups, respectively. Visual acuity (VA) with ETDRS 1.25% was lower in the DM1 patients. Both ETDRS 2.5% and color vision were lower in the DM1 group but did not reach statistical significance. Retinal thicknesses in the central area and in the vertical outer areas were higher in the DM1 group. Differences were found in the IRL with no changes in the outer ones. Long-term DM1 patients with no DR maintained visual function, with a decrease in VA with 1.25% ETDRS contrast. Macular thickness measurements were higher using Spectralis SD-OCT than DRI Triton SS-OCT, and DM1 patients had a decrease in IRL thickness, especially in the GCL at the parafoveal level, generating thinning of the RNFL in the peripheral areas. There were no differences in outer retinal layer (ORL) thickness.

Ophthalmic examination in the debut and during progression of neurodegenerative diseases

Neurodegenerative diseases (NDD) are a group of nosological forms, caused by excessive formation of protein molecules and their aggregates and leading to the death of brain cells. Classical pathophysiological mechanisms are associated with the accumulation of extracellular amyloid b -protein (A b) in Alzheimer's disease (AD) and a -synuclein protein in Parkinson's disease (PD), which are markers of neurodegenerative process. Signs of functional disorders in NDD include decreasing visual acuity, lower contrast light sensitivity with the most significant changes at the highest spatial frequencies (18 and 12 cycles per degree), and reduced color vision. These disorders correlate with the severity of cognitive impairment and duration of the disease. Changes in the indicators of psychophysical tests are accompanied by lower central retinal thickness (CRT), which is a consequence of inner layers degeneration. NDD progression is characterized by the stability of psychophysical tests, significant thinning of the peripapillary retinal nerve fiber layer (RNFL) and CRT thickening, which correlates with cognitive disfunction. A b and a -synuclein deposits in artery walls cause lumen narrowing and occlusion of blood vessels, reduced optic nerve disk perfusion density, superficial and deep capillary plexus depletion, expansion of the avascular foveolar zone. Microcirculatory disorders lead to retinal changes, which were proven to correlate negatively with the thickness of inner retinal layers and duration of the disease. An ever-growing need in the identification of specific and sensitive biomarkers at the preclinical stage of NDDs, differentiation of their causes, precise subtype classification, and assessment of progression risk is an evidence of the relevance of studying and identifying functional and structural changes in retinal neurons and axons. Non-invasive and informative methods of multimodal imaging appear to be valuable for NDD diagnosis and monitoring.

Quantitative assessment of retinal thickness and vessel density using optical coherence tomography angiography in patients with Alzheimer's disease and glaucoma.

PurposeAssessment and a direct comparison of retinal vessel density with the thickness of inner retinal layer (IRL) and outer retinal layer (ORL) in the same regions of the macula in subjects with Alzheimer’s disease (AD) and primary open-angle glaucoma (POAG).MethodsWe analyzed data from 48 eyes of healthy control (HC) participants, 71 eyes with POAG, and 49 eyes of AD patients. Ophthalmic examination included optical coherence tomography (OCT) imaging to measure IRL and ORL thickness and OCT angiography (OCTA) in the same region for the imaging of vessel density in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the retina. A direct comparison of vessel density and retinal layers thickness, which different dynamic ranges, was obtained by normalizing values as percentage losses.ResultsPatients with AD presented significantly greater losses of vascular density in the DVP and ORL thickness compared to POAG (p <0.001), but percentage losses of vessel density in SVP and IRL thickness were considerable in POAG compared to AD eyes (p<0.001). Positive associations among presence of AD were observed primarily in outer retina where a 1% decrease of ORL thickness was associated with about 24–29% increase in odds of the presence of AD. According to OCTA measurements, a 1% decrease of vessel density in DVP was positively associated with a 4–9% increase in odds of the presence of AD. In POAG positive associations among presence of disease were observed only in inner retina where 1% loss of IRL thickness and a 1% loss of vessel density in the SVP were positively associated with a 13–23% increase in risk of presence of the disease.ConclusionsAnalysis of ORL thickness and vessel density in DVP could potentially improve diagnostic capabilities and may provide a valuable approach for predicting of AD.

Foveal Differentiation and Inner Retinal Displacement Are Arrested in Extremely Premature Infants.

PurposeChildren with a history of prematurity often have poorly developed foveae but when during development foveal differences arise. We hypothesize that the course of foveal development is altered from the time of preterm birth.MethodsEyes of 102 preterm infants undergoing retinopathy of prematurity screening examinations in the STudy of Eye imaging in Premature infantS (BabySTEPS) (NCT02887157) were serially imaged between 30 and 42 weeks postmenstrual age (PMA) using handheld optical coherence tomography systems. Total retinal thickness, inner retinal layer (IRL) thickness, and outer retinal layer (ORL) thickness were measured at the foveal center and parafovea. Foveal put depth, IRL thickness, and ORL thickness were compared between infants born at different gestational ages using mixed effects models.ResultsFoveal pit depth and IRL thickness were inversely related to gestational age; on average, the most premature infants had the thickest IRL and shallowest pits at all PMAs. Differences were evident by 30 weeks PMA and persisted through 42 weeks PMA. The foveal pits of the most premature infants did not progressively deepen, and the IRLs did not continue to thin with increasing chronological age.ConclusionsFoveation in extremely preterm infants is arrested from the earliest observed ages and fails to progress through term equivalent age. The developmental displacement of the IRL from the foveal center into the parafovea does not occur normally after preterm birth. These observations suggest that foveal hypoplasia seen in children with history of prematurity is due to disturbances in foveal development that manifest within weeks of birth.

Microperimetry and Optical Coherence Tomography Changes in Type-1 Diabetes Mellitus without Retinopathy.

Background: We aimed to measure and correlate inner retinal layer (IRL) thickness and macular sensitivity by optical coherence tomography (OCT) and by microperimetry, respectively, in type 1 diabetes mellitus patients (DM1) without diabetic retinopathy (DR). Methods: Fifty-one DM1 patients and 81 age-matched healthy subjects underwent measurement of the axial length (AL), retinal thickness in the macular ETDRS areas by swept source (SS)-OCT and macular sensitivity by microperimeter. Results: The total retinal and IRL thicknesses were thicker in the DM1 group (p < 0.05) in practically all ETDRS areas, and they had a generalized decrease in sensitivity (p < 0.05) in 9 areas between both groups. There was a significant negative correlation between retinal sensitivity and age in all areas and in visual acuity (VA) in 5 out of the 9 areas for DM1 patients. Only a mild negative correlation was observed between retinal sensitivity in the 5° nasal inner (5NI) area and in IRL thickness in the temporal inner (TI) area (−0.309 with p = 0.029) in the DM1 group. Conclusion: Aging and disease evolution in DM1 patients without DR signs generate a decrease in retinal sensitivity. There was a direct relationship between retinal sensitivity and macular thickness in the DM1 group.

Foveal structure in nanophthalmos and visual acuity

PurposeTo evaluate the fovea in nanophthalmic eyes using spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA), and to investigate the relationship between the macular microstructure and visual acuity.MethodsThis is a retrospective case series of five nanophthalmic patients. The foveal avascular zone (FAZ) area was measured in superficial and deep vascular layers with OCTA. The thickness of the inner retinal layer (IRL) was measured with SD-OCT. The ratio of the foveal and parafoveal IRL thickness (fIRL/pIRL ratio) was calculated. The relationship between these parameters and visual acuity was then investigated.ResultsEight eyes were identified as nanophthalmic with a mean axial length of 17.19 ± 1.44 mm (range: 15.71 to 19.88 mm). The mean best-corrected visual acuity (BCVA) in the logarithm of the minimum angle of resolution (logMAR) was 0.12 ± 0.18 (range: − 0.18 to 0.40). OCTA showed that FAZs were either absent or undeveloped in the superficial and deep capillary plexuses. Two patients did not show any visual impairments despite small FAZ and a shallow foveal depression. Although the BCVA was significantly correlated with the deep FAZ size, it did not correlate with the superficial FAZ size, axial length, or fIRL/pIRL ratio. However, the refractive error, axial length, and deep FAZ size were all significantly correlated with the fIRL/pIRL ratio.ConclusionsThe FAZs were commonly found to be small in the superficial and deep capillary plexuses. Although the deep FAZ size correlated with visual acuity, it is unclear whether the retinal microstructure and the FAZ size are responsible for the visual impairments observed in the same individuals.

Long-Term Outcome of Epiretinal Membrane Surgery in Patients with Internal Limiting Membrane Dehiscence.

Purpose: To identify the effect of internal limiting membrane (ILM) dehiscence on surgical outcomes in eyes that have undergone epiretinal membrane (ERM) removal. Methods: Consecutive eyes with performed vitrectomy for ERM removal were included. Subjects were divided into two groups: patients with ILM dehiscence (group 1) and without ILM dehiscence (group 2). The best-corrected visual acuity (BCVA) and retinal layer thickness before and after surgery were compared between the two groups. Results: A total of 86 eyes were enrolled. Forty-six eyes (53.5%) showed ILM dehiscence before surgery. The baseline BCVAs were 0.46 ± 0.29 and 0.45 ± 0.25 in groups 1 and 2, respectively (p = 0.801). The BCVAs at 3, 6, and 12 months after surgery differed significantly between the two groups. The subfoveal thickness and inner retinal layer thickness (IRLT) of group 1 vs. 2 were 507.4 ± 80.0 vs. 417.6 ± 63.6 μm, and 270.2 ± 74.3 vs. 182.6 ± 60.4 μm, respectively (both p < 0.001). These differences between the groups remained significant until 12 months after surgery. In multivariate analyses, the location of ILM dehiscence (B = −0.105, p = 0.034) and final IRLT (B = 0.001, p = 0.046) were significant factors affecting the final BCVA. Conclusions: ILM dehiscence is a relatively common finding and associated with preoperative and postoperative increased IRLT, which results in worse surgical outcomes compared to the absence of ILM dehiscence in patients with ERM. Additionally, the final BCVA was significantly affected by its location and final IRLT in patients with ILM dehiscence.

Toll-like receptor-9 (TLR-9) deficiency alleviates optic nerve injury (ONI) by inhibiting inflammatory response in vivo and in vitro

Traumatic optic neuropathy is a common clinical problem. Damage to the optic nerve leads to shear stress and triggers secondary swelling within the optic canal. The study aims to explore the role of the inflammatory response following optic nerve injury (ONI) in toll-like receptor-9 knockout mice (TLR-9-/-) compared to wild-type mice (WT). At first, TLR-9-/- and WT mice were subjected to ONI. We then found that ONI significantly up-regulated TLR-9 expression levels in retinal tissues of WT mice. The retinal degeneration after ONI was alleviated in TLR-9-/- mice, as evidenced by the increased number of retinal ganglion cells (RGCs) and thickness of inner retinal layer (IRL). TUNEL staining and immunofluorescence staining of BRN3A indicated that TLR-9 knockout effectively improved the survival of RGCs. ONI-enhanced expression of Iba-1 and TMEM119 was markedly reduced in TLR-9-/- mice, indicating the suppression of microglial activation. Moreover, production of pro-inflammatory regulators, including inducible nitric oxide synthase (iNOS), macrophage chemo-attractant protein (MCP)-1, cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-18 and tumor necrosis factor-α (TNF-α), was significantly decreased in TLR-9-/- mice following ONI. TLR-9 knockout-attenuated inflammation was mainly through repressing myeloid differentiation factor 88 (MyD88) and IL-1 receptor-associated kinase 4 (IRAK4). Furthermore, ONI greatly up-regulated the protein expression levels of phosphorylated (p)-IKKα, p-IκBα and p-nuclear factor (NF)-κB, whereas being repressed in TLR-9-/- mice. The effects of TLR-9 on ONI were verified in lipopolysaccharide (LPS)-stimulated retinal microglial cells transfected with small interfering RNA TLR-9 (siTLR-9). As expected, promoting TLR-9 with its agonist markedly restored inflammation in TLR-9 knockdown cells stimulated by LPS. Therefore, all findings above suggested that suppressing TLR-9 showed neuroprotective effects against ONI through reducing inflammatory response, and TILR-9 might be a promising therapeutic target to develop effective strategies for the treatment of optic neuropathies.