Inner Retinal Layer Thickness Research Articles

Retinal Development in Infants and Young Children with Achromatopsia

Retinal Development in Infants and Young Children with Achromatopsia

Postoperative restoration of foveal inner retinal configuration in patients with epiretinal membrane and abnormally thick inner retina.

To investigate foveal inner retinal layer (IRL) restoration and its relationship with functional visual outcomes after membrane peeling in eyes with idiopathic epiretinal membrane (ERM) with foveal central thick IRL. Consecutive eyes (n = 57) with a thick foveal IRL that underwent 25-gauge vitrectomy for ERM treatment were included. Complete ophthalmic and spectral domain optical coherence tomography examinations were performed before and 1 year after surgery. Before surgery, mean best-corrected visual acuity (BCVA) was 20/48 (logMAR, 0.38); central foveal thickness, 515.0 ± 90.9 μm; and central IRL thickness (CIRLT) at the fovea, 167.7 ± 80.1 μm. One year after ERM peeling, mean BCVA improved to 20/30 (logMAR, 0.18), central foveal thickness to 404.1 ± 96.4 μm, and CIRLT to 76.8 ± 68.0 μm. In multivariate analysis, initial BCVA and CIRLT at baseline correlated well with final BCVA and BCVA improvement at 12 months. In comparison with Group B eyes (persistently thick foveal IRL at 12 months), Group A eyes (restored foveal IRL at 12 months) had thinner CIRLT at baseline and showed a significant post-surgical improvement in BCVA and metamorphopsia. In eyes with idiopathic ERM and decreased vision due to abnormally thick IRL in the foveal center, postoperative visual outcomes correlated well with preoperative CIRLT and postoperative restoration of IRL configuration after ERM peeling.

Improved analysis of the outer foveal microstructure ‐ OCT imaging of healthy and abnormal retina

AbstractPurpose To improve visualization and segmentation of the foveal photoreceptors from the level of outer segments to the synapse layer in the inner portion of the outer plexiform layer. Furthermore, to create a normative model of the topography of the outer nuclear layer (ONL) with cone and rod cell bodies and the Henle fiber layer (HFL) with the axons radiating out from the foveal center (FC). An improved separation of ONL and HFL is clinically relevant for the understanding of microstructural changes in abnormal retina.Methods Selected eyes from 14 normals and 5 young adults with a history of prematurity were imaged using a commercial spectral domain optical coherence tomography (SD‐OCT) system. Centered and displaced SD‐OCT entrance beam positions were used to obtain straight and tilted scans, respectively. Horizontal scans through FC with a distinct light reflex were selected for analysis. Straight and tilted SD‐OCT images were flattened to the RPE layer prior to registration and averaging. Retinal layer thickness was measured manually at FC and three lateral positions along the temporal and nasal hemi‐meridians.Results We found a close correspondence between layer thickness measurements at the same lateral positions for both straight and tilted scans. However, a discrepancy was found for the tilt‐up paracentral position for tilted scans, where the foveal slope appeared flatter and the thickness of inner retinal layers was lower than in the straight and tilt‐down positions.Conclusion Improved visualization of HFL/ONL was confirmed in tilted images. Image flattening and registration simplifies measurement of outer foveal layers in normal and abnormal retina.

Retinal neurodegenerative changes in the adult insulin receptor substrate-2 deficient mouse

Insulin receptor substrate-2 (Irs2) mediates peripheral insulin action and is essential for retinal health. Previous investigations have reported severe photoreceptor degeneration and abnormal visual function in Irs2-deficient mice. However, molecular changes in the Irs2−/− mouse retina have not been described. In this study, we examined retinal degenerative changes in neuronal and glial cells of adult (9- and 12-week old) Irs2−/− mice by immunohistochemistry. 9-week old Irs2−/− mice showed significant thinning of outer retinal layers, concomitant to Müller and microglial cell activation. Photoreceptor cells displayed different signs of degeneration, such as outer/inner segment atrophy, redistribution of rod- and cone-opsins and spatial disorganization of cone cells. This was accompanied by synaptic changes at the outer plexiform layer, including the retraction of rod-spherules, reduction of photoreceptor synaptic ribbons and synaptic remodeling in second order neurons (i.e. loss and sprouting of dendritic processes in rod bipolar and horizontal cells). By 12 weeks of age, the thickness of inner retinal layers was severely affected. Although inner plexiform layer stratification remained unchanged at this stage, rod bipolar cell axon terminals were significantly depleted. Significant loss of Brn3a+ retinal ganglion cells occurred in 12-week old Irs2−/− mice, in contrast to younger ages. Adult Irs2−/− mice showed clear hallmarks of neurodegeneration and disruption of the inner retina with increasing age. Pharmacological stimulation of Irs2 signaling pathway may provide additional neuroprotection in certain degenerative retinopathies.

Microperimetry, fundus autofluorescence, and retinal layer changes in progressing geographic atrophy

ObjectiveTo analyze correlation among microperimetry, inner and outer retinal layers, and fundus autofluorescence (FAF) changes in eyes with progressing geographic atrophy (GA) secondary to age-related macular degeneration. MethodsMicroperimetry, spectral-domain optical coherence tomography (SD-OCT), standard short-wavelength FAF (SW-FAF), and near-infrared-wavelength FAF (NIR-FAF) were performed for all patients at both baseline and follow-up visits. FAF pattern, integrity of photoreceptor inner segment/outer segment (IS/OS) junction, total retinal thickness (RT), inner retinal layers (IRL), and outer retinal layers (ORL) thickness changes of every microperimetry extrafoveal tested point were analyzed. ResultsA total of 366 microperimetry tested points were analyzed (6 patients, 7 eyes). Mean retinal sensitivity significantly decreased (p = 0.0149), and the percentage of dense scotomas significantly increased (p = 0.0125). Mean RT and mean ORL thickness significantly decreased (both p < 0.0001). Mean IRL thickness significantly increased (p = 0.0001). The decrease of ORL thickness was inversely correlated to the IRL thinning (rho = –0.710). FAF pattern at baseline was correlated to RT and ORL thickness (both p < 0.0001) and was significantly correlated to the risk to evolve to dense scotoma during follow-up (p = 0.0001 at SW-FAF, p < 0.0001 at NIR-FAF). Tested points showing at baseline the loss of photoreceptor IS/OS junction had a greater risk for evolving to dense scotoma compared with those with intact photoreceptor IS/OS junction (odds ratio 3.56, 95% CI 2.41–5.27). ConclusionsRetinal sensitivity changes are correlated to IRL and ORL thickness changes, and to photoreceptor IS/OS junction integrity. FAF patterns remain a relevant factor in predicting GA evolution. Microperimetry, SW-FAF and NIR-FAF, and SD-OCT should be combined to obtain adequate morphologic and functional prospective information.

Correlation of Inner Retinal Thickness Evaluated by Spectral-Domain Optical Coherence Tomography and Contrast Sensitivity in Parkinson disease

To compare inner retinal layer (IRL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and contrast sensitivity (CS) in patients with Parkinson disease (PD) and in healthy control (HC) subjects. Consecutive patients with and without PD were prospectively analyzed using SD-OCT and Pelli-Robson CS testing. SD-OCT IRL (ganglion-cell complex) thickness, consisting of the nerve fiber layer, ganglion cell layer, and inner plexiform layer, was segmented using an RTVue Model-RT100 with an EMM5 scan parameter covering a 5.0 × 5.0 mm cube centered on the fovea. Thickness voxel measurements at 0.25-mm intervals at sequential radial distances from the foveola were acquired horizontally and vertically. SD-OCT thickness raw data files were imported and analyzed within MATLAB (version 7.10.0). A database of CS scores and IRL thickness values by foveal location was constructed and statistically evaluated using JMP 10 (SAS Institute, Inc, Cary, NC). The results were compared between 28 eyes of 14 patients with PD and 28 eyes of 14 HC subjects. Controlling for age, mean CS scores of monocular right and randomized eyes were statistically lower in PD eyes (P < 0.05). IRL was significantly thinner in PD eyes than in HC eyes at several distances from the foveola (P < 0.05). The most numerous and significant thickness differences by diagnosis were located in the superior quadrant at a distance of 1.00-1.75 mm from the foveal center (17 μm; P < 0.01, maximum significant thickness difference and P value). Correlation was demonstrated between monocular CS and IRL thickness by diagnosis at multiple foveal locations for HC eyes as follows: nasal quadrant, 0.75-1.00 mm (P < 0.02); temporal quadrant, 0.50-1.00 mm (P < 0.05); superior quadrant, 1.00 mm (P < 0.05); and inferior quadrant, 1.00 mm (P < 0.03). No significant correlation was found between monocular CS and IRL thickness within PD subjects (P > 0.05 for each foveal location measured). CS and foveal IRL thickness are decreased in patients with PD. CS and IRL thickness correlated in HC subjects; however, no such correlation was demonstrated in PD. The functional deficit of dopaminergic interneurons, including amacrine cells, may outstrip the anatomic structural changes in the inner retina of PD patients. Inner retinal atrophic changes may underlie the pathogenesis of CS deficit and IRL thinning in PD.

Assessment of retinal layers and visual rehabilitation after epiretinal membrane removal

To evaluate the changes in visual acuity, metamorphopsia, and thickness of retinal layers after epiretinal membrane (ERM) removal and to investigate factors associated with visual function. This prospective study included 52 eyes of 52 patients who underwent surgery for idiopathic ERM. Changes in visual acuity, metamorphopsia score (M-score) using M-chart, and parafoveal thickness of each retinal layer were evaluated preoperatively and at 2-month and 6-month postoperative follow-up visits. Factors associated with visual acuity and M-score were investigated. Although continuous improvement in visual acuity and decrease in the thickness of parafoveal retinal layers following ERM removal was observed, relatively slow improvement in M-score was noted with values of 0.32 ± 0.27, 0.44 ± 0.46, and 0.23 ± 0.23, respectively at the defined time points. A preoperative increase in the thickness of parafoveal retina was mainly caused by increased thickness of inner retinal layers. Preoperative thickness of inner nuclear layer (INL) were closely associated with preoperative, postoperative visual acuity, and preoperative M-score (p = 0.001, 0.012, and 0.027, respectively). Compared with the postoperative improvement in visual acuity, the postoperative improvement in metamorphopsia was a rather slow process. Parafoveal INL thickness was found to be a significant structural factor for visual acuity and metamorphopsia in ERM.

Selective Over-Expression of Endothelin-1 in Endothelial Cells Exacerbates Inner Retinal Edema and Neuronal Death in Ischemic Retina

The level of endothelin-1 (ET-1), a potent vasoconstrictor, was associated with retinopathy under ischemia. The effects of endothelial endothelin-1 (ET-1) over-expression in a transgenic mouse model using Tie-1 promoter (TET-1 mice) on pathophysiological changes of retinal ischemia were investigated by intraluminal insertion of a microfilament up to middle cerebral artery (MCA) to transiently block the ophthalmic artery. Two-hour occlusion and twenty-two-hour reperfusion were performed in homozygous (Hm) TET-1 mice and their non-transgenic (NTg) littermates. Presence of pyknotic nuclei in ganglion cell layer (GCL) was investigated in paraffin sections of ipsilateral (ischemic) and contralateral (non-ischemic) retinae, followed by measurement of the thickness of inner retinal layer. Moreover, immunocytochemistry of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS) and aquaporin-4 (AQP4) peptides on retinal sections were performed to study glial cell reactivity, glutamate metabolism and water accumulation, respectively after retinal ischemia. Similar morphology was observed in the contralateral retinae of NTg and Hm TET-1 mice, whereas ipsilateral retina of NTg mice showed slight structural and cellular changes compared with the corresponding contralateral retina. Ipsilateral retinae of Hm TET-1 mice showed more significant changes when compared with ipsilateral retina of NTg mice, including more prominent cell death in GCL characterized by the presence of pyknotic nuclei, elevated GS immunoreactivity in Müller cell bodies and processes, increased AQP-4 immunoreactivity in Müller cell processes, and increased inner retinal thickness. Thus, over-expression of endothelial ET-1 in TET-1 mice may contribute to increased glutamate-induced neurotoxicity on neuronal cells and water accumulation in inner retina leading to edema.

Visual loss after use of intraocular silicone oil associated with thinning of inner retinal layers

To investigate the incidence and cause of severe visual loss following use and removal of intraocular silicone oil (SiO) after uncomplicated vitrectomy and SiO injection for primary rhegmatogenous retinal detachment (RRD). Consecutive case series of 216 patients operated with vitrectomy for primary RRD in 2004-2005. In 162 eyes, SiO (5500 centiStoke) had been used as intravitreal tamponade and in 54 eyes gas (perflouropropane, C(3) F(8) ) had been used. Following chart review, we identified 16 eyes in 16 patients (nine SiO eyes, seven gas eyes) with macula-on and documented visual acuity ≥6/12 before surgery, where SiO had been removed, cataract surgery performed and no re-detachment had occurred. Examinations included best-corrected visual acuity (BCVA) and high-definition optical coherence tomography (OCT) of the macular area. Preoperative characteristics were identical between SiO and gas eyes. Postoperative BCVA was significantly worse in SiO eyes (>6/24) compared to gas eyes (>6/7.5), p = 0.005. Three of 9 (33%) SiO eyes had final BCVA ≤6/60 and 67% had final BCVA ≤6/12. No gas eyes had final BCVA <6/9. Macular OCT revealed thinning of inner retinal layers in SiO-operated eyes (5148 pixels) compared to gas-operated eyes (6897 pixels), p < 0.002. No other visually significant structural differences were found. Severe visual loss after SiO use was observed in 1/3 of patients with otherwise good visual potential. The visual loss was associated with a significant reduction in inner retinal thickness indicating neuronal cell loss in the macular area as a possible explanation.

Three-Dimensional Imaging of Macular Inner Structures in Glaucoma by Using Spectral-Domain Optical Coherence Tomography

To profile macular thickness changes in glaucoma by using three-dimensional spectral-domain optical coherence tomography (3D-SD-OCT). The study included 30 eyes with suspected glaucoma and preperimetric glaucoma (SGPPG) and 35 healthy eyes. The macular thickness, including those of the total retina, nerve fiber layer (NFL), and combined inner retinal layers (IRLs)-NFL+ganglion cell layer (GCL)+inner plexiform layer (IPL)-was measured by 3D-SD-OCT raster scans in a 6 mm(2) region. The average and sectoral thicknesses were calculated on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart and a ETDRS chart with a 45° rotation (glaucoma sector chart, GSC). The mean IRL thickness was significantly less in the SGPPG eyes than in the healthy eyes, but the mean total retinal and macular NFL thicknesses were not. In the SGPPG eyes, the IRLs were thinner in the outer macula than in the inner macula, in the inferior hemisphere than in the superior hemisphere, and in the temporal hemisphere than in the nasal hemisphere. The significantly thinned sectors were nearly identical on the GSC but only slightly overlapped on the ETDRS chart. The IRLs in the inferior temporal outer sector (GSC) had the greatest area under the receiver operating characteristic curve, which was significantly greater than those for the IRLs over the entire macula, inferior hemiretinal region, and inferior outer hemicircular region (macular subfields), and that for the circumpapillary NFL in the inferior sectors (P = 0.001-0.036). Macular IRL thickness measured by using 3D-SD-OCT is useful for profiling macular atrophy in SGPPG.

Correlation between spectral domain optical coherence tomography findings and visual outcomes in central retinal vein occlusion

Purpose:To investigate the relationship between spectral domain optical coherence tomography (SD-OCT) findings and visual outcomes following resolution of macular edema in central retinal vein occlusion (CRVO).Methods:Patients with recent onset CRVO who had undergone SD-OCT and fluorescein angiography (FA) exams on the day of initial presentation were included. All patients had resolution of macular edema in SD-OCT images at the end of follow-up, and they were separated into two groups according to final visual acuity: group 1 (≤20/200) and group 2 (>20/200). SD-OCT scans and FA studies were analyzed in a masked fashion. Macular perfusion status by FA was categorized according to presence or absence of macular ischemia.Results:A total of 22 eyes from 22 patients [mean age 53.0 ± 15.0 (standard deviation)] were included. Mean follow up period was 14.6 ± 8.1 (standard deviation) months. Group 1 (10 eyes) had significantly higher rates of residual intraretinal fluid, loss of foveal inner segment/outer segment (IS/OS) junction line and loss of inner retinal layers in late stage SD-OCT images (P = 0.027) when compared with group 2 (12 eyes). Loss of foveal IS/OS junction line (odds ratio [OR] = 13.826; P = 0.098) and loss of inner retinal layers (OR = 38.908; P = 0.013) in late stage SD-OCT images were correlated with poorer final visual outcomes. Macular ischemia by FA correlated with thinner central subfield thickness (r = −0.54, P = 0.021) and loss of inner retinal layers (r = 0.47, P = 0.031) in early stage SD-OCT images; and presence of residual intraretinal fluid (r = 0.61, P = 0.003) and loss of inner retinal layers (r = 0.71, P < 0.001) in late stage SD-OCT images.Conclusion:Loss of foveal IS/OS junction line and inner retinal layers on SD-OCT significantly correlated with poorer visual outcomes in CRVO patients.

Detection of retinal changes in Parkinson's disease with spectral-domain optical coherence tomography

PurposeThis pilot study investigated whether high-resolution spectral-domain optical coherence tomography (SD-OCT) could detect differences in inner retinal layer (IRL), peripapillary retinal nerve fiber layer (RNFL), and macular thickness between patients with Parkinson’s disease (PD) and controls.MethodsBoth eyes of patients with PD and age-matched controls were imaged with the Heidelberg Spectralis® HRA + OCT. RNFL, IRL, and macular thickness were measured for each eye using Heidelberg software. These measurements were compared with validated, published normal values for macular and RNFL thickness, and compared with matched controls for IRL thickness.ResultsEighteen eyes from nine subjects with PD and 19 eyes of 16 control subjects were evaluated using SD-OCT. The average age of PD patients was 64 years with a range of 52–75 years. The average age of controls was 67 years with a range of 50–81 years. No significant reduction in IRL thickness was detected between PD patients and age-matched controls at 13 points along a 6 mm horizontal section through the fovea. No significant difference in RNFL thickness was detected between PD patients and published normal values. Overall average RNFL thickness was 97 μm for PD patients, which exactly matched the normative database value. However, significant differences in macular thickness were detected in three of nine subfields between PD subjects and published normal values. In PD subjects, the outer superior subfield was 2.8% thinner (P = 0.026), while the outer nasal and inner inferior subfields were 2.8% (P = 0.016) and 2.7% (P = 0.001) thicker compared to published normal values.ConclusionIn this pilot study, significant differences in macular thickness were detected in three of nine subfields by SD-OCT. However, SD-OCT did not detect significant reductions in peripapillary RNFL and IRL thickness between PD patients and controls. This suggests that macular thickness measurements by SD-OCT may potentially be used as an objective, noninvasive, and easily quantifiable in vivo biomarker in PD. Larger, longitudinal studies are needed to explore these relationships further.

A Pilot Study of Fourier-Domain Optical Coherence Tomography of Retinal Dystrophy Patients

To characterize the macular anatomy of retinal dystrophy eyes using high-speed, high-resolution, Fourier-domain optical coherence tomography (FD-OCT). Case-control study. Retinal dystrophy patients and normal age- and gender-matched controls underwent FD-OCT imaging using the RTVue (Optovue Inc., Fremont, California, USA). Vertical and horizontal 8-mm scans of 1024 lines/cross-section were obtained. Based on boundaries manually drawn on computer displays of OCT cross-sections, the thicknesses of the retina, inner retinal layer (IRL), and outer retinal layer (ORL) were averaged over both 5-mm (macular) and 1.5-mm (foveal) regions centered at the fovea. The IRL was the sum of nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) thicknesses. Total retinal thickness (RT) was measured between the internal limiting membrane (ILM) and the retinal pigment epithelium. ORL thickness was calculated by subtracting IRL thickness from RT. Fourteen patients (three retinitis pigmentosa, two cone-rod degeneration, two Stargardt disease, and seven normal controls) underwent FD-OCT imaging. Mean foveal RT was 271.3 +/- 23.3 microm for controls and 158.4 +/- 47.1 microm for retinal dystrophy patients (P < .001). Mean macular RT was 292.8 +/- 8.1 microm for controls and 199.1 +/- 32.6 microm for retinal dystrophy patients (P < .001). Mean macular ORL was 182.9 +/- 4.7 microm for controls and 101.3 +/- 18.7 microm for retinal dystrophy patients (P < .001); mean macular IRL was 109.9 +/- 6.4 microm for controls and 97.9 +/- 20.7 microm for retinal dystrophy patients (P = .06). Eyes with retinal dystrophy had a small (11%) decrease in macular IRL and severe (45%) decrease in macular ORL compared to normal controls.

Pentoxifylline Decreases Up-Regulated Nuclear Factor kappa B Activation and Cytokine Production in the Rat Retina following Transient Ischemia

Aim: To investigate whether pentoxifylline (PTX) could influence the increased cytokine gene expression in the retina flowing transient ischemia, and if so, whether it acts through the modulation of nuclear factor kappa B (NF-ĸB) activation. Methods: Sprague-Dawley rats were randomly divided into three equal groups: control group, saline-treated group, and PTX-treated group. Increased intraocular pressure was applied for 90 min to induce retinal ischemia, and reperfusion was established by lowering the bottle to eye level. The reperfusion period lasted for 48 h. In the PTX-treated group, an initial dose of 20 mg PTX was injected via tail vein at the beginning of reperfusion. Then the rat received infusion of PTX at a rate of 6 mg/kg/h throughout the entire reperfusion period. The retinal tissues were collected at the end of 1, 6, 12, 24, and 48 h of reperfusion, respectively, for biochemical analysis. Histological examination was done on the tissues collected at the end of 48 h after reperfusion. Results: Histological examination revealed reduction of overall retinal thickness and thinning of the inner retinal layer in saline-treated rats after 48-hour reperfusion. However, PTX treatment significantly reduced the loss of overall retinal thickness and thinning of inner retinal layers. Dramatic increase in NF-ĸB activation, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production and mRNA expression were observed in the saline-treated group after reperfusion, with the peak reached around 12 h. In the PTX-treated group, NF-ĸB activation, TNF-α and IL-1β production and mRNA expression were significantly reduced at each corresponding time point compared to the saline-treated group. Conclusion: PTX decreased the up-regulated activation of NF-ĸB and the expression of proinflammatory cytokines, TNF-α and IL-1β in rat retinas following ischemia/reperfusion. This may contribute to significantly reduce the loss of overall retinal thickness and thinning of inner retinal layers.

Pressure-Induced Retinal Ischemia in Rats: An Experimental Model for Quantitative Study

The advent of treatment modalities with the potential to ameliorate retinal ischemic injury calls for methods allowing their quantitative assessment. We thus established a model of pressure-induced retinal ischemia/reperfusion injury in rats. The intraocular pressure (IOP) was raised to 110 mm Hg by cannulation of the anterior chamber for a duration of 0, 90 or 120 min. The eyes were reperfused for 3 or 7 days. Morphologically, retinal injury occurred in a pattern consistent with retinal and choroidal vascular occlusion. Damage increased in severity with prolonged durations of ischemia. Morphometric determination of the mean thickness of inner retinal layers (MTIRL) revealed significant differences between controls and the 90- or 120-min ischemia groups (p less than 0.05 and p less than 0.01, respectively). The difference in MTIRL between 3 and 7 days of reperfusion was not significant. Replacement of normal saline by a solution of 5% dextrose in the hydrostatic device used to increase the IOP led to a decrease in retinal injury after 120 min of ischemia (p less than 0.01). This model combines a relatively simple methodology, cost-effective execution and a fast, semicomputerized method of quantitation. Depletion of carbohydrates during ischemia may contribute to retinal injury in this model.