Outer Nuclear Layer Thickness Research Articles

Cone Structure and Function in RPGR- and USH2A-Associated Retinal Degeneration

To compare cone structure and function between RPGR- and USH2A-associated retinal degeneration. Retrospective, observational, cross-sectional study. This multicenter study included 13 eyes (9 participants) with RPGR-related X-linked retinitis pigmentosa (RPGR), 15 eyes (10 participants) with USH2A-related Usher syndrome type 2 (USH2), 16 eyes (9 participants) with USH2A-related autosomal recessive retinitis pigmentosa (ARRP), and 7 normal eyes (6 participants). Structural measures included cone spacing and density from adaptive optics scanning laser ophthalmoscopy and photoreceptor inner segment (IS), outer segment (OS), and outer nuclear layer (ONL) thickness from optical coherence tomography (OCT) images. OCT angiography images were used to study choriocapillaris flow deficit percent (CCFD). Cone function was assessed by fundus-guided microperimetry. Measures were compared at designated regions using analysis of variance with pairwise comparisons among disease groups, adjusted for disease duration and eccentricity. OCT segmentation revealed shorter OS and IS, with reduced ONL thickness in RPGR compared to normal (OS: P < .001, IS: P=.001, ONL: P=.005), USH2 (OS: P=.01, IS: P=.03, ONL: P=.03), or ARRP (OS: P=.001, ONL: P=.03). Increased cone spacing was observed in both RPGR (P=.03) and USH2 compared with normal (P=.048). The mean CCFD in RPGR was greater than in USH2 (P=.02). Microperimetry demonstrated below-normal regional sensitivity in RPGR (P=.004), USH2 (P=.02), and ARRP (P=.009), without significant intergroup differences. Outer retinal structure and choriocapillaris perfusion were more abnormal in RPGR- than USH2A-related retinal degenerations, whereas there were no significant differences in below-normal regional sensitivity between each rod-cone degeneration associated with variants in these 2 genes expressed at the photoreceptor-connecting cilium.

Ageing changes in retinal outer nuclear layer thickness and cone photoreceptor density using adaptive optics-free imaging.

To investigate age-related changes of the outer nuclear layer (ONL) thickness and cone density, and their associations in healthy participants using a modified, narrow scan-angle Heidelberg Retina Angiograph (HRA2). Retinal cones were imaged outside the fovea at 8.8° eccentricity and cone density was compared to ONL thickness measurements obtained by Spectral-Domain Optical Coherence Tomography (SD-OCT) at the same locations. Fifty-six eyes of 56 healthy participants with a median age (interquartile range, IQR) of 37 years (29-55) were included. Median (IQR) cone count was 7,472 (7,188, 7,746) cones/mm2 and median (IQR) ONL thickness was 56 (52, 60) µm for healthy participants. Both cone density and ONL thickness were negatively associated with age: cone density, R2 = 0.16 (F(1,54) = 10.41, P = 0.002); ONL thickness, R2 = 0.12 (F(1,54) = 7.41, P = 0.009). No significant association was seen between cone density and ONL thickness (R2 = 0.03; F(1,54) = 1.66, P = 0.20). Cone density was lower, and ONL thinner, in older compared to younger participants, therefore, image-based structural measures should be compared to age-related data. However, cone density and ONL thickness were not strongly associated, indicating that determinants of ONL thickness measurements other than cone density measurements, and including measurement error, have a major influence.

Photoreceptor outer segment layer thinning as a biomarker in acute central serous chorioretinopathy.

The photoreceptor outer segment (PROS) layer demonstrates focal thinning above the fluorescein leakage in acute central serous chorioretinopathy (CSC); however, the nature of this phenomenon is not known. To study the relationship between the PROS layer and thickness of the outer retinal layers above the fluorescein leakage in newly diagnosed acute CSC. Single-center retrospective study. All participants received multimodal imaging, including fluorescein angiography and optical coherence tomography. Thickness of PROS, outer nuclear layer (ONL), and ONL-outer plexiform layer (OPL) complex was measured above the leakage and outside the leakage within the area of neurosensory detachment. The number of intraretinal hyperreflective foci of the outer retina was counted. The correlation between PROS thickness and ONL, OPL-ONL complex thickness, and the number of intraretinal hyperreflective foci was calculated. Fifty eyes of 48 patients (38 males and 10 females, 43.8 ± 10.6 years) with a mean symptom duration of 1.4 ± 1.3 months were included. PROS thickness above the fluorescein leakage showed a statistically significant correlation with ONL thickness, OPL-ONL complex thickness, and the number of hyperreflective foci in the outer retina, 0.57, 0.60, and -0.46, respectively (p < 0.001). Measuring the extent of PROS thinning above the leakage in newly diagnosed CSC allowed to predict self-resolution of subretinal fluid. The greatest linear dimension of PROS thinning showed an area under the receiver operating curve (ROC) curve of 0.98. The cases without PROS thinning had the fastest resolution of subretinal fluid. PROS thinning above the fluorescein leakage in acute CSC is associated with thinning of the outer retinal layers and reveals mild outer retinal atrophy. The absence of PROS thinning predicts faster resolution of CSC.

Assessment of early and long-COVID related retinal neurodegeneration with optical coherence tomography.

The aim of this study is to investigate short-term and long-term effects of coronovirus 19 disease (COVID-19) at inner and outer retinal layers of patients recovered from COVID-19 with Spectral Domain Optical Coherence Tomography (SD-OCT) and compare these to healthy subjects. Twenty-seven patients recovered from COVID-19, and age- and gender-matched 27 healthy controls were included in this study. Macular and peripapillary retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL) were analyzed with SD-OCT 1 month (V1 visit) and 12 months (V2 visit) after negative result of reverse transcriptase-polymerase chain reaction test. Macular RNFL thickness in outer ring was thinner at V1 and V2 visits than healthy control (p = 0.049 and p = 0.005). Central and inferonasal quadrants of peripapillary RNFL thicknesses were reduced at V1 and V2 visits compared to controls (p = 0.001 and p = 0.024 for V1 visit; p = 0.001 and p = 0.006 for V2 visit). Thinning in ONL thickness in inner ring was observed at V1 and V2 visits than healthy subjects (p = 0.006 and p = 0.001). Subclinical localized changes in macular and peripapillary RNFL and outer nuclear layer were demonstrated in early and 12-months follow-up after COVID-19 recovery.

Retinal Thinning in Adults with Autism Spectrum Disorder

Since the retina shares its embryological origin with the central nervous system, optical coherence tomography (OCT), an imaging technique frequently employed in ophthalmology to analyze the macula and intraretinal layer thicknesses and volumes, has recently become increasingly important in psychiatric research. We examined 34 autistic and 31 neurotypical adults (NT) using OCT. Autistic adults had reduced overall macular and outer nuclear layer (ONL) thickness and volume compared to NT. Both macular and ONL thickness showed significant inverse associations with the severity of autistic symptoms measured with the Social Responsiveness Scale 2 (SRS-2). Longitudinal studies across different age groups are required to clarify whether retinal changes may represent a possible trait marker.

Deep Capillary Plexus Features in Acute Macular Neuroretinopathy: Novel Insights Based on the Anatomy of Henle Fiber Layer.

The purpose of this study was to identify a precise location of deep capillary plexus (DCP) injury in acute macular neuroretinopathy (AMN) lesions using multimodal imaging. En face structural optical coherence tomography (OCT) images were manually segmented to delineate outer retinal AMN lesions involving the ellipsoid zone and interdigitation zone. AMN lesion centroid was calculated, and image distortion was applied to correct for Henle fiber layer (HFL) length and orientation. The resulting image was registered with the corresponding en face OCT angiography (OCTA) image segmented at the DCP and structural OCT volume before grading for vascular and structural features, respectively. Thirty-nine AMN lesions from 16 eyes (11 female patients, mean age 34 ± 4 years) were analyzed. After correcting for HFL anatomy, in 62% of AMN lesions, the centroid co-localized with a capillary vortex (pattern 1); flow defects were detected in 33% of lesions (pattern 2); and in 5% of lesions no specific pattern could be identified (pattern 3). The detection of a specific pattern increased after correcting the projection of AMN lesion for HFL anatomy (28% vs. 5%, P = 0.04). Outer nuclear layer thickness was lower in the centroid area in 10 (29%) AMN lesions from 6 patients, all corresponding to lesions fitting pattern 2 (r = 0.78, P < 0.001). AMN lesions might be a result of DCP impairment at the level of the capillary vortex or draining venule. In eyes with AMN, the location of outer retinal changes associated with DCP ischemia appears to be influenced by the length and orientation of HFL.

Retinal development and the expression profiles of opsin genes during larval development in Takifugu rubripes.

The light-sensitive capacity of fish larvae is determined by the structure of the retina and the opsins expressed in the retinal and nonretinal photoreceptors. In this study, the retinal structure and expression of opsin genes during the early developmental stage of Takifugu rubripes larvae were investigated. Histological examination showed that at 1 days after hatching (dah), seven layers were observed in the retina of T. rubripes larva, including the pigment epithelial layer [retinal pigment epithelium layer (RPE)], photoreceptor layer (PRos/is), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL) and ganglion cell layer (GCL). At 2dah, optic fibre layer (OFL) can be observed, and all eight layers were visible in the retina. By measuring the thickness of each layer, opposing developmental trends were found in the thickness of ONL, OPL, INL, IPL, GCL and OFL. The nuclear density of ONL, INL and GCL and the ratios of ONL/INL, ONL/GCL and INL/GCL were also measured and the ratio of ONL/GCL ranged from 1.9 at 2dah to 3.4 at 8dah and no significant difference was observed between the different developmental stages (P > 0.05). No significant difference was observed for the INL/GCL ratio between the different developmental stages, which ranged from 1.2 at 2dah to 2.0 at 18 dah (P > 0.05). The results of quantitative real-time polymerase chain reaction (PCR) showed that the expression of RH1, LWS, RH2-1, RH2-2, SWS2, rod opsin, opsin3 and opsin5 could be detected from 1dah. These results suggest that the well-developed retina and early expression of the opsins of T. rubripes during the period of transition from endogenous to mixed feeding might be critical for vision-based survival skills during the early life stages after hatching.

RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History

To review and describe in detail the clinical course, functional and anatomic characteristics of RP2-associated retinal degeneration. Retrospective case series. Male participants with disease-causing variants in the RP2 gene. Review of all case notes and results of molecular genetic testing, retinal imaging (fundus autofluorescence [FAF] imaging, OCT), and electrophysiology assessment. Molecular genetic testing, clinical findings including best-corrected visual acuity (BCVA), qualitative and quantitative retinal imaging analysis, and electrophysiology parameters. Fifty-four molecularly confirmed patients were identified from 38 pedigrees. Twenty-eight disease-causing variants were identified, with 20 not previously clinically characterized. Fifty-three patients (98.1%) presented with retinitis pigmentosa. The mean age of onset (range ± standard deviation [SD]) was 9.6 years (1-57 ± 9.2 years). Forty-four patients (91.7%) had childhood-onset disease, with mean age of onset of 7.6 years. The most common first symptom was night blindness (68.8%). Mean BCVA (range ± SD) was 0.91 logarithm of the minimum angle of resolution (logMAR) (0-2.7 ± 0.80) and 0.94 logMAR (0-2.7 ± 0.78) for right and left eyes, respectively. On the basis of the World Health Organization visual impairment criteria, 18 patients (34%) had low vision. The majority (17/22) showed electroretinogram (ERG) evidence of a rod-cone dystrophy. Pattern ERG P50 was undetectable in all but 2 patients. A range of FAF findings was observed, from normal to advanced atrophy. There were no statistically significant differences between right and left eyes for ellipsoid zone width (EZW) and outer nuclear layer (ONL) thickness. The mean annual rate of EZW loss was 219 μm/year, and the mean annual decrease in ONL thickness was 4.93 μm/year. No patient with childhood-onset disease had an identifiable ellipsoid zone (EZ) after the age of 26 years at baseline or follow-up. Four patients had adulthood-onset disease and a less severe phenotype. This study details the clinical phenotype of RP2 retinopathy in a large cohort. The majority presented with early-onset severe retinal degeneration, with early macular involvement and complete loss of the foveal photoreceptor layer by the third decade of life. Full-field ERGs revealed rod-cone dystrophy in the vast majority, but with generalized (peripheral) cone system involvement of widely varying severity in the first 2 decades of life. Proprietary or commercial disclosure may be found after the references.

The quantitative evaluation of retinal layers after resolution of subretinal fluid in acute central serous chorioretinopathy.

To evaluate the average retinal layer thicknesses in eyes with unilateral acute central serous chorioretinopathy (CSC) (with subretinal fluid (SRF)) and after complete resolution of SRF in these eyes and to compare the results with those obtained in healthy eyes. Fifty-four eyes of 27 patients with unilateral acute CSC (CSC in active phase) who had complete resolution of SRF and 25 eyes of 25 healthy control subjects enrolled in this retrospective study. The average thicknesses of the retinal layers were measured by segmentation analysis of optical coherence tomography at baseline and 6 months after complete resolution of SRF. The mean outer nuclear layer (ONL) thickness was significantly lower in eyes with CSC than in fellow eyes (p < 0.001). The mean ONL thickness was increased after resolution of SRF, but still low compared to unaffected fellow eye and the increment was not statistically significant (p > 0.05). There were significant strong inverse correlations between visual acuity and ONL thicknesses at baseline and 6 months after complete resolution of SRF (p < 0.001, r = - 0.810; p < 0.001, r = - 0.705, respectively). ONL thickness was thinned in cases with acute CSC, and although there was some increment in ONL thickness 6 months after complete resolution of SRF, it was still thinner compared to unaffected fellow eyes.

Measurement of Foveal Retinal Thickness in Myopic Patients Using Different Display Modes on Optical Coherence Tomography: A Retrospective, Cross-Sectional Study.

The aim of this work is to investigate the differences in the measurement of foveal retinal thickness in myopic patients between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT). Horizontal OCT line scan through the central fovea was used for manual measurement of foveal retinal thickness under the two display modes, and the values were compared using Wilcoxon signed-rank test. Correlations between the OCT image tilting angle (OCT ITA) and differences in OCT measurement were analyzed by Spearman's test. 127 participants with a median age of 28years, a median spherical equivalent (SE) of - 8.5 D, and a median axial length (AL) of 27.04mm. There were significant differences between the two display modes, with a median absolute difference (median relative difference) of 13.33μm (2.75%) for the central foveal thickness (CFT), 5.33μm (1.28%) for the Henle fiber and outer nuclear layer thickness (HFL + ONL), 3μm (6.47%) for the external limiting membrane to ellipsoid zone distance (ELM-EZ), and 4μm (8.77%) for the ellipsoid zone to retinal pigment epithelium distance (EZ-RPE) (all p < 0.05). The differences in foveal retinal thickness between the two display modes were significantly correlated with the OCT ITA (r = 0.732 for CFT, 0.561 for HFL + ONL, 0.642 for ELM-EZ, and 0.471 for EZ-RPE, all p < 0.05). Disparities between the two display modes were found in the manual measurement of foveal retinal thickness and correlated to the OCT ITA.

Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy

Preservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial (NCT02503332). Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16°-contour-line at month 12. Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16° contour-line compared to the pooled sham arm (mean difference [95% CI] + 0.29 z-score units [0.16, 0.42], P < 0.001). The same was evident for eyes treated with pegcetacoplan every other month (+ 0.26 z-score units [0.13, 0.4], P < 0.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16°-contour-line at month 12. These findings suggest that pegcetacoplan could slow GA progression and lead to reduced thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.

Visual function and retinal changes after voretigene neparvovec treatment in children with biallelic RPE65-related inherited retinal dystrophy

To report quantitative retinal changes assessed by spectral-domain optical coherence tomography (SD-OCT) in children treated with voretigene neparvovec (VN) at a single center in Italy. Retrospective review of six consecutive pediatric patients with biallelic RPE65-related dystrophy treated bilaterally with VN. SD-OCT scans were analyzed to extract Early Treatment Diabetic Retinopathy Study (ETDRS) thickness maps of the whole retina and the outer nuclear layer (ONL). Changes in visual function were assessed by best-corrected visual acuity (BCVA) and retinal morphology at Days 30/45 and 180. BCVA significantly improved at Day 30/45 and 6 months (both P < 0.001). Central foveal retinal thickness and central foveal ONL thickness tended to increase (6.4 ± 19.2 µm; P = 0.080 and 3.42 ± 7.68 µm; P = 0.091, respectively). ONL thickness of the internal ETDRS-ring significantly increased at day 30/45 (4.7 ± 8.4 µm; P < 0.001) and day 180 (5.0 ± 5.7 µm; P = 0.009). Intra-operative foveal detachment was not associated with a higher function gain in terms of BCVA, but with a mild thinning of foveal ONL after treatment. The improvement of BCVA and thickening of the ONL layer suggest that improvement of visual acuity could be related to partial recovery of retinal morphology in the perifoveal ring.

Influence of Preoperative Foveal Layers' Thickness on Visual Function and Macular Morphology by Phacovitrectomy for Epiretinal Membrane.

The aim of this retrospective study with short, differently dispersed follow-up is to record the relationships between the pathologies of the individual foveal layers, measured by spectral domain optical coherence tomography (SD-OCT), and to investigate their influence on pre- and postoperative best-corrected decimal far visual acuity (BCVA) by phacovitrectomy for epiretinal membrane (ERM) in comorbidity with cataract. Patients and Methods. 208 eyes of 173 patients with symptomatic idiopathic ERM and moderate cataract were included. In all OCT morphological stages of ERM, as well as in their combination with macular lamellar hole (MLH) and vitreomacular traction (VMT), a significant difference in the thickness of the individual fovea layers was found. In addition, the entire fovea thickening led to the proportional thickening of the individual fovea layers (p < 0.001). The larger the central foveolar (CFT, R 2 = -0.238, p=0.002), maximum foveal (MFT, R 2 = -0.267, p=0.001), and ONL thickness (R 2 = -0.16, p=0.044) were preoperatively, the worse the initial visual acuity was at all OCT stages of ERM. This was even more significant in the presence of a tractive component in the case of MLH or VMT (p < 0.001). In ERM without a traction component, only ONL thickening led to significant postoperative visual acuity reduction (R 2 = -0.163, p=0.047). The foveolar retinal thickening (CFT and MFT) of the pure ERM is directly associated with distortion of the retinal layers (R 2 = 0.292, p < 0.001 and R 2 = 0.287, p < 0.001) as well as with separation of the ERM (R 2 = 0.168, p=0.034 and R 2 = 0.187, p=0.018). When ERM was combined with tractive component, CFT, ONL, and INL thickness correlated (positively) with the integrity of ellipsoid zone (R 2 = 0.342, p < 0.05) and external limiting membrane (R 2 = 0.548, p < 0.001). ONL thickening in ERM without a tractive component serves as a limited prognostic factor of postoperative visual acuity decrease. The preoperative BCVA in the groups of ERM with traction component showed significant correlation with CFT as well as with the thickness of individual foveal layers. VMT in ERM correlates with the disintegration of the ellipsoid zone.

Longitudinal Evaluation of Changes in Retinal Architecture Using Optical Coherence Tomography in Achromatopsia.

PurposeThis prospective study investigates longitudinal changes in retinal structure in patients with achromatopsia (ACHM) using optical coherence tomography (OCT).MethodsSeventeen patients (five adults, 12 children) with genetically confirmed CNGA3- or CNGB3-associated ACHM underwent ocular examination and OCT over a follow-up period of between 2 and 9.33 years (mean = 5.7 years). Foveal tomograms were qualitatively graded and were segmented for quantitative analysis: central macular thickness (CMt), outer nuclear layer thickness (ONLt), and size of the foveal hyporeflective zone (vertical HRZ thickness: HRZt and horizontal HRZ width: HRZw) were measured. Data were analyzed using linear mixed regression models. Both age and visit were included into the models, to explore the possibility that the rate of disease progression depends on patient age.ResultsFifteen of 17 patients (88%) showed longitudinal changes in retinal structure over the follow-up period. The most common patterns of progression was development of ellipsoid zone (EZ) disruption and HRZ. There was a significant increase in HRZt (P = 0.01) and HRZw (P = 0.001) between visits and no significant change in CMt and ONLt. Retinal parameters showed no difference in changes by genetic mutation (CNGA3 (n = 11), CNGB3 (n = 6)).ConclusionsThis study demonstrates clear longitudinal changes in foveal structure mainly in children, but also in adults with ACHM, over a long follow-up period. The longitudinal foveal changes suggest that treatment at an earlier age should be favored.

Correlation between Choroidal Vascularity Index and Outer Retina in Patients with Diabetic Retinopathy.

The choroid supplies blood to the outer retina. We quantified outer retinal and choroidal parameters to understand better the pathogenesis of diabetic retinopathy (DR) and diabetic macular edema (DME). The retrospective cross-sectional single-center study included 210 eyes from 139 diabetic patients and 76 eyes from 52 healthy controls. Spectral-domain optical coherence tomography (OCT) was carried out with a Spectralis HRA + OCT imaging device. The outer retinal layer (ORL), outer nuclear layer (ONL), and choroidal thicknesses were assessed along with the choroidal vascularity index (CVI). The presence of DR, whether with DME or without, was associated with choroidal thinning (p < 0.001). Compared with the controls, patients with DR without DME presented with lower ORL and ONL thickness (p < 0.001), whereas those with DR and DME had higher values of both parameters (p < 0.001). Significant correlations between outer retinal and choroidal parameters were found only in patients with DR without DME (ORL with choroidal thickness: p = 0.003, rho = 0.34; ORL with CVI: p < 0.001, rho = 0.49, ONL with CVI: p < 0.027, rho = 0.25). No correlations between choroidal and outer retinal parameters were observed in the controls and patients with DR and concomitant DME. Aside from diabetic choroidopathy, other pathogenic mechanisms seem to predominate in the latter group.

The effects of hyperbaric oxygen therapy on retinal layers in healthy eyes

Purpose: The aim of our study is to investigate the effects of hyperbaric oxygen (HBO2) therapy on retinal layers in healthy eyes. Method: Thirty patients who were taken to outpatient HBO2 for any indication were included in the study. All patients underwent 10 sessions of HBO2; 20 healthy patients were taken as the control group. We used the spectral-domain optical coherence tomography (SD-OCT) to obtain automated measurements of thickness for each retinal layer – i.e., 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) and retinal pigment epithelium (RPE) – and to conduct foveal (central 1 mm), inner-ring (parafoveal 1 to 3mm), and outer-ring (perifoveal 3 to 6mm) retinal layer measurements. Retinal OCT scans were performed before HBO2, after the first and 10th sessions. All retinal layer thicknesses were assessed with SD-OCT software system and compared between each visit. Retinal thicknesses were calculated in the central, inner ring and outer ring subfields (nine quadrants). Results: In SD-OCT measurements, there were no statistically significant difference before HBO2, after the first and 10th sessions in terms of foveal, inner-ring and outer-ring thickness of RNFL, GCL, IPL, INL, OPL, ONL and RPE. Conclusions: Our study demonstrated that there was no change in the thickness of the retinal layers after the first and 10th sessions in healthy eyes.

Longitudinal Photoreceptor Phenotype Observation and Therapeutic Evaluation of a Carbonic Anhydrase Inhibitor in a X-Linked Retinoschisis Mouse Model.

PurposeTo study the long-term photoreceptor changes and to evaluate the effects of topical application of a carbonic anhydrase inhibitor (CAI) in a mouse model of X-linked retinoschisis (XLRS).MethodsConventional electroretinograms (ERGs) and dark-adapted 10-Hz flicker ERGs were recorded in control and Rs1−/Y mice generated with CRISPR/Cas9. ON-pathway blocker 2-amino-4-phosphobutyric acid (APB) was injected intravitreally. Morphology was evaluated with histology and optical coherence tomography (OCT). Mice were treated with a CAI inhibitor brinzolamide eye drops (10 mg/ml) three times a day for 3 months. OCT and ERG findings at 1, 4, and 10 months were analyzed.ResultsNegative ERGs and retinal cavities were evident in Rs1−/Y mice. Both a-wave and b-wave amplitudes decreased with age when compared with age-matched controls. The APB-isolated a-wave (a′) amplitudes of Rs1−/Y mice were reduced in all age groups. In dark-adapted 10-Hz flicker ERG, the amplitude-intensity curve of Rs1−/Y mice shifted down. The thickness of ONL and IS/OS decreased in Rs1−/Y mice. CAI reduced the splitting retinal cavities but didn't affect the ERG.ConclusionsIn addition to post receptoral impairments, photoreceptor cells underwent progressive dysfunction since early age in Rs1−/Y mice. Long-term CAI treatment improved the shrinkage of the splitting retinal cavity, while no functional improvement was observed.

Comparison of long-term visual and anatomical outcomes between internal limiting membrane flap and peeling techniques for macular holes with a propensity score analysis.

To compare visual and anatomical outcomes between internal limiting membrane (ILM) flap (IF) and peeling (IP) techniques for full-thickness macular holes (FTMHs). A retrospective case series with propensity-score matching (PSM). Patients with a minimum 12 months follow-up were divided into IF and IP groups and matched based on FTMH size and preoperative best-corrected visual acuity (BCVA). BCVA and optical coherence tomography (OCT) findings were obtained to assess outer retinal layer integrity, foveal thickness, and foveal displacement. Twenty-six eyes were included in each group after PSM. The IF group showed significantly greater BCVA after 1 month, its corresponding change from preoperative BCVA, proportions of eyes with ellipsoid zone defects <250 μm after 1 month, and interdigitation zone restoration after 6 and 12 months (P = 0.007, 0.038, 0.048, 0.025, and 0.023, respectively), as well as less foveal gliosis after 1, 3, 6, and 12 months (P = 0.020, 0.017, 0.050, and 0.024, respectively). In the IP group, the mean outer nuclear layer thickness significantly decreased at 3 (P = 0.019) and 12 months (P = 0.016) compared to 1 month, and the foveal displacement toward the optic disc was significant after 1, 3, 6, and 12 months (P = 0.049, 0.006, 0.001, and <0.001, respectively). Compared to IP, IF promoted faster recovery of BCVA and outer retinal layers and was more protective against postoperative foveal thinning and displacement; hence, it should be considered for small and large FTMHs.

Comparison of Each Retinal Layer Thicknesses between Eyes with Central Retinal Vein Occlusion and Normal Contralateral Eyes.

PurposeTo evaluate the difference in each retinal layer thickness in central retinal vein occlusion (CRVO) with resolved macular edema after intravitreal antivascular endothelial growth factor injection and normal contralateral eyes..MethodsPatients with ischemic and nonischemic CRVO whose macular edema resolved after intravitreal antivascular endothelial growth factor injections and did not recur for at least 6 months, and a normal contralateral eye were enrolled. Each retinal layer thickness between CRVO and normal contralateral eyes was compared according to Early Treatment Diabetic Retinopathy Study subfields using spectral domain optical coherence tomography.ResultsThe thicknesses of outer nuclear layer, photoreceptor layer, and retinal pigment epithelium in central ring, ganglion cell layer, inner plexiform layer, outer nuclear layer, and photoreceptor layer in the inner ring, and ganglion cell layer in the outer ring of CRVO eyes were significantly thinner than those of normal contralateral eyes (all p < 0.05). Whereas, inner nuclear layer and outer plexiform layer thicknesses in central ring of CRVO eyes were 23.86 ± 8.8 and 25.76 ± 7.6 μm, respectively, which was significantly thicker than those of normal contralateral eyes (19.52 ± 7.7 and 22.76 ± 6.5 μm; p = 0.019 and p = 0.043, respectively). Additionally, the mean best-corrected visual acuity of CRVO eyes were significantly correlated with photoreceptor layer thickness in central ring (p = 0.005).ConclusionsIn CRVO eyes with resolved macular edema, the outer retinal layers were thinner as well as inner retinal layers, whereas inner plexiform layer and outer nuclear layer were thicker than normal fellow eyes. Additionally, photoreceptor layer thickness in foveal area had a significant impact on visual acuity in CRVO.

MACULAR PIGMENT OPTICAL DENSITY ASSESSED BY HETEROCHROMATIC FLICKER PHOTOMETRY IN EYES AFFECTED BY PRIMARY EPIRETINAL MEMBRANE.

To compare macular pigment optical density (MPOD) in healthy eyes versus eyes affected by primary epiretinal membrane (ERM) in different stages and to assess the relation between MPOD and optical coherence tomography findings. Prospective cross-sectional study of 62 eyes of 62 patients affected by unilateral primary ERM. Contralateral healthy eyes from the same patients were used as a control group. Main outcome measures were MPOD, ERM stage, central foveal thickness (CFT), outer nuclear layer thickness (ONLT), integrity of outer retinal bands, and presence of central bouquet abnormalities. In the study group, mean CFT was 444 ± 75 μm and mean ONLT was 245 ± 40 μm, whereas in the control group, mean CFT was 230 ± 21 μm and mean ONLT was 102 ± 14 μm (P < 0.001). Mean MPOD was 0.86 ± 0.07 in eyes with ERM and 0.48 ± 0.09 in contralateral healthy eyes (P < 0.001). Macular pigment optical density was associated with CFT (P = 0.006) and ONLT (P < 0.001), whereas no significant associations were observed between MPOD and outer retinal bands integrity (P = 0.14) and central bouquet abnormalities (P = 0.08). Macular pigment optical density increased in eyes affected by primary ERM proportionally to CFT and, especially, ONLT. Probably, centripetal forces exerted by ERM contraction on the retinal surface lead to a progressive foveal packing of foveal Müller cells.