Photoreceptor Outer Segment Layer Research Articles

Thickened photoreceptor outer segment layer in children with hyperopic anisometropic amblyopia.

To quantitatively investigate the reflectivity and structure of the outer retinal layers in children with hyperopic anisometropic amblyopia by using swept-source optical coherence tomography (SS-OCT). Seventy-eight patients with amblyopia and 64 age-matched children with normal vision were included in this study. All participants underwent SS-OCT and detailed ophthalmic examinations. Longitudinal reflectance profile measurements were measured using Image J. The reflectivity of outer retinal layers was measured at the three selected positions: subfovea, 1 mm nasal to the fovea, and 1 mm temporal to the fovea. The reflectivity ratios were calculated by outer retinal layers divided by the nuclear layer (ONL) for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the amblyopia and normal controls. The possible effects of age, sex, and axial length on results were adjusted by generalized estimating equations. Photoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41 ± 1.83 vs. 16.84 ± 1.39, P < 0.001 at the fovea; 14.78 ± 1.34 vs. 14.19 ± 1.40, P = 0.030 at 1 mm nasal to the foveal; 14.92 ± 1.48 vs. 14.41 ± 1.32, P = 0.049 at 1 mm temporal to the fovea). The reflectivity ratio of outer segment/ONL was higher only at 1 mm nasal to the fovea (2.94 ± 0.61 vs. 2.70 ± 0.42, P = 0.02). Subfoveal OS thickness was positively correlated with choroidal thickness (r = 0.248, P = 0.018) but was not correlated with spherical equivalent, age, axial length, or logMAR visual acuity. Quantitative measurement of SS-OCT images revealed greater photoreceptor outer segments in both eyes of children with amblyopia than in normal control eyes. A thicker OS thickness is somehow related to amblyopia, and this may be a new useful diagnostic parameter for amblyopia.

A Photodynamic Therapy Index for Central Serous Chorioretinopathy to Predict Visual Prognosis Using Pretreatment Factors

This study aimed to establish a treatment index based on functional outcomes of photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). A retrospective clinical case-control study. This was a single-institute study. Eighty eyes with CSC, who are treated by PDT and whose subretinal fluid resolves within six months, were divided into two groups: those with poor visual outcome (PVO) (best-corrected visual acuity [BCVA] ≤0.5 six months post-PDT), and the remaining eyes (better visual outcome [BVO]). The areas under the curve (AUC) and cutoff values from receiver operating characteristic curves were examined. This was used to predict the groups using pretreatment BCVA and the thickness of each retinochoroidal layer. Twenty-one eyes were in the PVO group and 59 eyes in the BVO group. The AUCs were 0.959 for BCVA, 0.959 for the thickness from the internal limiting membrane to the external limiting membrane (IET), 0.820 for the thickness from the external limiting membrane to the photoreceptor outer segment layer, 0.715 for the subfoveal retinal thickness, and 0.515 for the subfoveal choroidal thickness. The BCVA and IET cut-off values were 0.267 logMAR and 71.5 μm, respectively. Using the combination of the cutoff values of BCVA and IET, the highest values for the sensitivity, specificity, positive predictive value, and negative predictive value were 95.2%, 94.9%, 85.0%, and 98.0%, respectively. The combination of pre-PDT BCVA and IET in CSC can accurately predict the post-treatment visual prognosis. These values could be used as a treatment index of PDT for CSC.

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.

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.

Leopard spot chorioretinopathy revealing late onset sympathetic ophthalmia

AbstractPurposeTo report a case of a very late onset atypical sympathetic ophthalmia presented as a leopard spot retinopathy.MethodsAn observational case report of a 64‐year‐old patient with a history of penetrating ocular trauma of the right eye (RE) at the age of 3‐year‐old who presented with visual blurring of the left eye (LE). The patient underwent complete ophthalmic examination, autofluorescence imaging, fluorescein angiography, Indocyanine Green (ICG) angiography, swept‐source optical coherence tomography (SS‐OCT).ResultsExamination of the RE showed a phthisis bulbi. Visual acuity of the LE was limited to hand motion. Slit lamp examination revealed +1 cells anterior chamber inflammation, granulomatous keratic precipitates, posterior synechiae, with a mild cataract and +2 vitreous cells. Fundoscopy showed multiple yellowish patchy subretinal lesions. Fluorescein angiography revealed hyperfluorescent nummular areas at early frames without late leakage surrounded by zones of hypofluorescences. Fundus autofluorescence imaging showed a leopard spot pattern with areas of hypoautofluorescence surrounded by hyperautofluorescence. ICG angiography showed no hypofluorescent dark dots. SS‐OCT demonstrated retinal thickening, multiple areas of flat subretinal fluid, irregular hyperreflective spots at the photoreceptor outer segment layer and irregularities of the retinal pigment epithelium. The diagnosis of unilateral diffuse uveal melanocytic proliferation (DUMP) was first made. The patient underwent a systemic workup with full‐body computed tomography scans, cerebral and ocular magnetic resonance imaging and blood tests including tumor markers. All tests were normal. The patient was put on oral prednisone (1 mg/kg/day) during 6 months with a gradual tapering and good initial outcome. Visual acuity increased to 40/200.Two weeks after stopping steroids, he presented with acute granulomatous anterior uveitis and the diagnosis of very late onset sympathetic ophthalmia was made.ConclusionsLeopard retinopathy can be an uncommon clinical presentation of a variety of disorders especially sympathetic ophthalmia. The diagnosis could be challenging in case of atypical presentation and very late onset. Treatment outcome and close follow‐up should be considered for a correct diagnosis.

Complement factor H deficiency combined with smoking promotes retinal degeneration in a novel mouse model.

Age-related macular degeneration is the leading cause of blindness in the elderly. The Y402H polymorphism in complement factor H promotes disease-like pathogenesis, and a Cfh+/- murine model can replicate this phenotype, but only after two years. We reasoned that by combining CFH deficiency with cigarette smoke exposure, we might be able to accelerate disease progression to facilitate preclinical research in this disease. Wild-type and Cfh+/- mice were exposed to nose-only cigarette smoke for three months. Retinal tissue morphology and visual function were evaluated by optical coherence tomography, fundus photography and autofluorescence, and electroretinogram. Retinal pigment epithelial cell phenotype and ultrastructure were evaluated by immunofluorescence staining and transmission electron microscopy. Cfh+/- smoking mice showed a dome-like protruding lesion at the ellipsoid zone (drusen-like deposition), many retinal hyper-autofluorescence spots, and a marked decrease in A- and B-wave amplitudes. Compared with non-smoking mice, wild-type and Cfh+/- smoking mice showed sub-retinal pigment epithelium complement protein 3 deposition, activation of microglia, metabolic waste accumulation, and impairment of tight junctions. Microglia cells migrated into the photoreceptor outer segment layer in Cfh+/- smoking mice showed increased activation. Our results suggest that exposing Cfh+/- mice to smoking leads to earlier onset of age-related macular degeneration than in other animal models, which may facilitate preclinical research into the pathophysiology and treatment of this disease.

Age-related changes in the rhesus macaque eye

PurposeTo assess age-related changes in the rhesus macaque eye and evaluate them to corresponding human age-related eye disease. MethodsData from eye exams and imaging tests including intraocular pressure (IOP), lens thickness, axial length, and retinal optical coherence tomography (OCT) images were evaluated from 142 individuals and statistically analyzed for age-related changes. Quantitative autofluorescence (qAF) was measured as was the presence of macular lesions as related to age. ResultsAges of the 142 rhesus macaques ranged from 0.7 to 29 years (mean = 16.4 years, stdev = 7.5 years). Anterior segment measurements such as IOP, lens thickness, and axial length were acquired. Advanced retinal imaging in the form of optical coherence tomography and qAF were obtained. Quantitative assessments were made and variations by age groups were analyzed to compare with established age-related changes in human eyes. Quantitative analysis of data revealed age-related increase in intraocular pressure (0.165 mm Hg per increase in year of age), ocular biometry (lens thickness 7.2 μm per increase in year of age; and axial length 52.8 μm per increase in year of age), and presence of macular lesions. Age-related changes in thicknesses of retinal layers on OCT were observed and quantified, showing decreased thickness of the retinal ganglion cell layer and inner nuclear layer, and increased thickness of photoreceptor outer segment and choroidal layers. Age was correlated with increased qAF by 1.021 autofluorescence units per increase in year of age. ConclusionsThe rhesus macaque has age-related ocular changes similar to humans. IOP increases with age while retinal ganglion cell layer thickness decreases. Macular lesions develop in some aged animals. Our findings support the concept that rhesus macaques may be useful for the study of important age-related diseases such as glaucoma, macular diseases, and cone disorders, and for development of therapies for these diseases.

Photoreceptor outer segment layer contributes to optical coherence tomography signal attenuation beneath neurosensory detachments.

To establish the factors responsible for attenuation of the optical coherence tomography (OCT) signal beneath the neurosensory detachment (NSD). We retrospectively reviewed 33 eyes with acute central serous chorioretinopathy. The thickness of the neurosensory retina, the thickness of the photoreceptor outer segment (PROS) layer, the height of the NSD, and the reflectivity of the underlying retinal pigment epithelium (RPE) were measured at selected points of B-scans exported from 6 × 6 mm OCT angiography protocols. The intensity of the flow signal was measured at the corresponding regions of the choriocapillaris slab. The correlation between the parameters of the NSD and both the reflectivity of underlying RPE and the intensity of the flow signal in the choriocapillaris was calculated. Correlation coefficients between RPE reflectivity and neurosensory retinal thickness, PROS layer thickness, and NSD height were -0.32, -0.64, and -0.25, respectively (p < 0.001). Correlation coefficients between the intensity of the flow signal and neurosensory retinal thickness, PROS layer thickness, and NSD height were -0.24 (p = 0.004), -0.52 (p < 0.001), and 0.13 (p = 0.13), respectively. The thickness of the PROS layer is the most significant factor affecting OCT signal at the level of RPE and OCT angiography flow signal in the choriocapillaris beneath the NSD.

Reduced photoreceptor outer segment layer thickness and association with vision in amblyopic children and adolescents with unilateral high myopia

Purpose To quantitatively compare reflectivity and other morphological changes of the photoreceptors of normal eyes with amblyopic eyes using the longitudinal reflectance profile (LRP) on swept-source optical coherence tomography (SS-OCT) images in children and adolescents with unilateral high myopia. The relationships between OCT parameters and visual acuity were investigated. Method Twenty-six amblyopes with unilateral high myopia and 34 age-, axial length- and spherical equivalent-matched normal controls were recruited. All participants underwent SS-OCT and detailed ophthalmic investigations. The reflectivity of the outer retinal and photoreceptor outer segment layer thickness were quantified by LRP using ImageJ software. All parameters were measured at three selected regions: at the fovea, 1 mm nasal to the fovea and 1 mm temporal to the fovea. Differences between the groups were evaluated. Results The mean choroidal thickness was thinner in amblyopic eyes compared with controls (165.19±59.02 μm vs 214.97±66.41 μm at the fovea; 128.77±57.06 μm vs 161.54±57.37 μm at 1 mm nasal to the fovea; 188.13±59.51 μm vs 219.87±61.78 μm at 1 mm temporal to the fovea, P<0.05). The amblyopic eyes had higher reflectivity of the ellipsoid zone at 1 mm nasal to the fovea only (85.41±25.78 vs 70.76±18.69, P=0.02). The mean length of the photoreceptor outer segment (OS) layer was significantly greater in the control eyes than in the amblyopic eyes at all three regions (20.19±1.89 vs 18.70±2.23 at the fovea, P=0.006; 16.06±1.47 vs 15.07±1.30 at 1 mm nasal to the fovea, P=0.008; 15.81±1.58 vs 14.56±1.87 at 1 mm temporal to the fovea, P=0.006). The shortened OS length was associated with poorer visual acuity. Conclusion The results of this study revealed that the amblyopes with unilateral high myopia had thinner choroidal thickness and shortened OS thickness compared to normal controls. The findings indicate that abnormal anatomic changes in the amblyopic children and adolescents with unilateral high myopia were not only due to high myopia but more likely due to a combination of high myopia and amblyopia.

Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank

AimTo examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses.MethodsWe included 115 954 UK Biobank participants aged 40–69...

AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model

Loss of Crumbs homolog 1 (CRB1) or CRB2 proteins in Müller cells or photoreceptors in the mouse retina results in a CRB dose-dependent retinal phenotype. In this study, we present a novel Müller cell-specific Crb1KOCrb2LowMGC retinitis pigmentosa mouse model (complete loss of CRB1 and reduced levels of CRB2 specifically in Müller cells). The Crb double mutant mice showed deficits in electroretinography, optokinetic head tracking, and retinal morphology. Exposure of retinas to low levels of dl-α-aminoadipate acid induced gliosis and retinal disorganization in Crb1KOCrb2LowMGC retinas but not in wild-type or Crb1-deficient retinas. Crb1KOCrb2LowMGC mice showed a substantial decrease in inner/outer photoreceptor segment length and optokinetic head-tracking response. Intravitreal application of rAAV vectors expressing human CRB2 (hCRB2) in Müller cells of Crb1KOCrb2LowMGC mice subsequently exposed to low levels of dl-α-aminoadipate acid prevented loss of vision, whereas recombinant adeno-associated viral (rAAV) vectors expressing human CRB1 (hCRB1) did not. Both rAAV vectors partially protected the morphology of the retina. The results suggest that hCRB expression in Müller cells is vital for control of retinal cell adhesion at the outer limiting membrane, and that the rAAV-cytomegalovirus (CMV)-hCRB2 vector is more potent than rAAV-minimal CMV (CMVmin)-hCRB1 in protection against loss of vision.

The qualitative assessment of optical coherence tomography and the central retinal sensitivity in patients with retinitis pigmentosa.

To analyze the relationships between qualitative and quantitative parameters of spectral-domain optical coherence tomography (SD-OCT) and the central retinal sensitivity in patients with retinitis pigmentosa (RP). Ninety-three eyes of 93 patients were finally enrolled, with a median age (quartile) of 58 (24.5) years. We assessed the patients using SD-OCT and the 10-2 program of a Humphry Field Analyzer (HFA). As a qualitative parameter, two graders independently classified the patients' SD-OCT images into five severity grades (grades 1-5) based on the severity of damage to the photoreceptor inner and outer segments (IS/OS) layer. As quantitative parameters, we measured the IS-ellipsoid zone (IS-EZ) width, IS/OS thickness, outer nuclear layer (ONL) thickness, central macular thickness (CMT, 1 and 3 mm) and macular cube (6 × 6 mm) volume and thickness. The central retinal sensitivity was defined by the best-corrected visual acuity (BCVA; logMAR), average sensitivities of the central 4 (foveal sensitivity [FS]) and 12 (macular sensitivity [MS]) points of the HFA 10-2 program and the mean deviation (MD) of the 10-2 program. Spearman's correlation was used to assess the association between both qualitative and quantitative parameters and variables of the central retinal sensitivity. In addition, we performed a multiple regression analysis using these parameters to identify the parameters most strongly influencing the central retinal sensitivity. The IS/OS severity grade was significantly correlated with the BCVA (ρ = 0.741, P < 0.001), FS (ρ = -0.844, P < 0.001), MS (ρ = -0.820, P < 0.001) and MD (ρ = -0.681, P < 0.001) and showed stronger correlations to them than any other quantitative parameters including the IS-EZ width, IS/OS thickness, ONL thickness, CMTs and macular cube volume/thickness. Furthermore, a step-wise multiple regression analysis indicated that the IS/OS severity grade was more strongly associated with the BCVA (β = 0.659, P < 0.001), FS (β = -0.820, P < 0.001), MS (β = -0.820, P < 0.001) and MD (β = -0.674, P < 0.001) than any other quantitative parameters. The intraclass correlation coefficient between two graders indicated substantial correlation (κ = 0.70). The qualitative grading of OCT based on the severity of the IS/OS layer was simple and strongly correlated with the central retinal sensitivity in patients with RP. It may be useful to assess the central visual function in patients with RP, although there is some variation in severity within the same severity grade.

Reduced photoreceptor outer segment layer thickness in mild commotio retinae without ellipsoid zone disruption.

To quantitatively investigate the reflectivity and structure of the outer retinal layers on spectral-domain optical coherence tomography (SD-OCT) in commotio retinae. Nineteen patients with acute macular commotio retinae and 19 age-matched normal controls were examined using SD-OCT. Longitudinal reflectance profiles (LRP) were obtained using Image J. The reflectivity of outer retinal layers was measured at the fovea, 1mm nasal to fovea and 1mm temporal to fovea. The reflectivity ratios of outer retinal layers divided by the outer nuclear layer (ONL) were calculated for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the patients and controls. The reflectivity ratio of ellipsoid zone/ONL and outer segment/ONL was higher in commotio retinae than in controls only at fovea (12.66 ± 4.73 vs 9.67 ± 3.34, p = 0.041; 7.70 ± 2.20 vs 3.73 ± 1.63, p < 0.001, respectively) but not at 1mm nasal or temporal to the fovea. Photoreceptor outer segment layer thickness was significantly shorter in commotio retinae compared to controls at all three locations (19.64 ± 3.05 vs 25.16 ± 3.53, 16.95 ± 4.02 vs 20.00 ± 3.00, and 15.42 ± 3.22 vs 20.05 ± 2.48, respectively, all p < 0.05). Quantitative measurement of SD-OCT images revealed that shortening of photoreceptor outer segment is an additional, and potentially better, biomarker for commotio retinae on top of increased reflectivity.

Diffuse Outer Layer Opacification: A Novel Finding in Patients With Autosomal Recessive Bestrophinopathy.

Purpose:Autosomal recessive bestrophinopathy (ARB) is a rare inherited retinal dystrophy resulted from mutations in bestrophin-1 (BEST1) which affect functioning of the retinal pigment epithelium (RPE). Descriptions of disease findings in patients with ARB to date have focused only on macular changes. In this case series, we report previously undescribed mid-peripheral retinal changes occurring in 4 patients with ARB.Design:Case series.Methods:A single-center, retrospective review of medical records from Mayo Clinic patients with ARB was performed. Imaging reviewed include fundus photography, fundus autofluorescence, spectral domain optical coherence tomography (OCT), and fluorescein angiography. Demographic information and disease progression were noted.Results:4 affected patients from 3 families were identified. All 4 patients were female, and mean age was 12.5 years (range 5–19 years). Diffuse mid-peripheral whitening was consistently noted on fundus photography. Concomitant OCT imaging demonstrated areas of hyperreflectivity in the photoreceptor outer segment layer in areas corresponding to whitening seen on fundus photography. In 1 patient who was followed for 12 years, this finding persisted. Subretinal fluid was also consistently present. Other pathologic imaging findings observed in each patient were in agreement with previous reports of ARB.Conclusions:This is the first descriptive report of pathologic findings occurred beyond the posterior pole in patients with ARB. These mid-peripheral retinal changes potentially imply that the entirety of the RPE is affected by mutations in BEST1, as also suggested by previous electro-oculogram (EOG) findings. Such implications will be important when developing treatment trials, as past trials have focused only on the posterior pole of the RPE.

Clinical Application of Fluorescein Angiography-Free Navigated Focal Laser Photocoagulation in Central Serous Chorioretinopathy.

To present clinical application of fluorescein angiography (FA)-free focal laser photocoagulation (FLP) of the leakage point in patients with central serous chorioretinopathy (CSC). A prospective case series included 16 eyes of 16 patients with non-resolved CSC. The leakage point was identified with optical coherence tomography (OCT) as a small single pigment epithelium detachment (PED) localized in the upper half of the neurosensory detachment with an area of photoreceptor outer segments layer thinning above this PED. FLP was performed with the Navilas 532 system. All patients achieved complete resolution of the subretinal fluid within a mean time of 6.5 ± 1.8 weeks. The mean best-corrected visual acuity statistically significantly increased from 0.08 ± 0.09 (20/25) at baseline to 0.0 ± 0.04 (20/20) at 2 months after FLP (P = .0005). FA-free, OCT-guided navigated FLP is an effective and safe option to treat a significant number of patients with CSC. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e118-e124.].

Retinal structural-vascular-functional relationship using optical coherence tomography and optical coherence tomography \u2013 angiography in myopia

BackgroundTo examine the retinal structure–vascular-function relationship using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in myopia.MethodsThis was a prospective cross-sectional study comprising 86 eyes of 45 individuals with varying axial lengths and spherical equivalents and no posterior segment abnormalities. All eyes underwent optical coherence tomography with the Spectralis SD-OCT and OCTA with RTVue-XR Avanti; Optovue. Individual macular retinal layer thicknesses and flow areas and vessel densities were measured on OCT and OCTA, respectively. Linear correlations were made between the macular layer thicknesses, flow areas and vessel densities with axial length, spherical equivalent and visual acuity.ResultsThe participants’ mean ages were 33.34 ± 14.45 years, mean spherical equivalent refractions were − 7.17 ± 5.71 D and axial lengths were 25.95 ± 2.41 mm. There were significant positive correlations of foveal angle (r = 0.757, p = 0.001), inner retinal (r = 0.764, p = 0.001) and outer plexiform layer (r = 0.771, p = 0.001) thickness on OCT and vessel densities in deep capillary plexus (r = 0.313, p = 0.003) on OCTA with axial length and negative correlations with spherical equivalents and visual acuity. Significant negative correlations of outer nuclear layer (r = − 0.560, p = 0.03) and photoreceptor outer segment layer thickness (r = − 0.856, p < 0.001) were noted on OCT with axial length and positive correlations with spherical equivalents and visual acuity.ConclusionThe lateral retinal stretching in myopia could possibly explain the correlation between retinal layer thickness, vascular density and visual acuity in these eyes. Further research is required to investigate this.

Quantitative Assessment of Outer Retinal Layer and Photoreceptor Outer Segment Layer and Their Relation to Visual Acuity in Diabetic Macular Edema.

Purpose To compare outer retinal layer (ORL) thickness and photoreceptor outer segment (PROS) length between normal eyes and eyes with diabetic macular edema (DME), and also, to study the correlation between central macular thicknesses (CMT), ORL, and PROS length with best corrected visual acuity (BCVA) in DME. Methods 80 eyes were included in the study; they were divided into two groups, group Ι (40 normal eyes) and group ΙΙ (40 eyes) with DME. Complete ophthalmic examination and OCT were done for all eyes. Comparison between ORL and PROS was done between both groups; also, correlation between ORL thickness, PROS length, and CMT with BCVA in group ΙΙ was studied. Results CMT was greater in group ΙΙ than group Ι (392.70 ± 62.91 and 265.73 ± 17.17, respectively) (SS, p < 0.001). ORL thickness was statistically significantly greater in group Ι than group ΙΙ (104.80 ± 4.94, 93.68 ± 6.34, p < 0.001). Regarding PROS length, it was statistically significantly greater in group Ι than group ΙΙ (31.38 ± 3.4 and 26.65 ± 3.39, respectively, p < 0.001). There was moderate correlation between BCVA and ORL thickness (r = −0.440, p=0.004) and strong correlation between BCVA and PROS length in group ΙΙ (r = − 0.690, p < 0.001), while there was weak correlation between BCVA and CMT (r = 0.198, p=0.220). Conclusion Both ORL thickness and PROS length were greater in healthy normal eyes than eyes with DME. BCVA was correlated better with PROS length and ORL thickness than CMT.

The Spectral-Domain Optical Coherence Tomography Findings Associated with the Morphological and Electrophysiological Changes in a Rat Model of Retinal Degeneration, Rhodopsin S334ter-4 Rats.

Purpose To characterize the spectral-domain optical coherence tomography (SD-OCT) findings of the rhodopsin S334ter transgenic rats (line 4) in relation to the morphologic and electroretinographic features. Materials and Methods Rhodopsin S334ter transgenic rats (line 4) were employed as a model of retinal degeneration. The Sprague-Dawley (SD) rats were used as a wild-type control. SD-OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA) was performed on the S334ter rats (line 4) from postnatal days (P) 13−110. The longitudinal changes of the SD-OCT images were analyzed both qualitatively and quantitatively in comparison to those of SD rats. The SD-OCT images were also compared to the histological and electron microscopic findings from examination performed on P 22, 36, and 61. Full field combined rod and cone electroretinography (ERG) was performed and the relationship between the thickness of the retinal sublayers and the amplitudes of the a- and b-waves was further analyzed. Results The photoreceptor inner and outer segment layer became diffusely hyperreflective in the SD-OCT images of the S334ter rats; these findings were not observed in the SD rats. This hyperreflective change corresponded to the degenerated inner and outer segments and the accumulation of the extracellular vesicles in the interphotoreceptor matrix. Quantitatively, the retinal outer sublayer and the photoreceptor sublayer in the S334ter rats became progressively thinner in comparison to those in the SD rats; the difference was statistically significant. The amplitudes of both the a- and b-waves on ERG were severely deteriorated in the S334ter rats. Discussion The SD-OCT images in the S334ter rats noninvasively provided information regarding the pathological changes in the photoreceptors and the longitudinal changes of both qualitative and quantitative changes during retinal degeneration in the S334ter rats (line 4). The pathological features of the photoreceptor inner and outer segments can be detected on SD-OCT as diffuse hyperreflective changes in the photoreceptor layer.

Association between Visual Acuity and Retinal Layer Metrics in Diabetics with and without Macular Edema

Purpose Diabetes is known to cause alterations in retinal microvasculature and tissue that progressively lead to visual impairment. Optical coherence tomography (OCT) is useful for assessment of total retinal thickening due to diabetic macular edema (DME). In the current study, we determined associations between visual acuity (VA) and retinal layer thickness, reflectance, and interface disruption derived from enface OCT images in subjects with and without DME. Materials and Methods Best corrected VA was measured and high-density OCT volume scans were acquired in 149 diabetic subjects. A previously established image segmentation method identified retinal layer interfaces and locations of visually indiscernible (disrupted) interfaces. Enface thickness maps and reflectance images of the nerve fiber layer (NFL), combined ganglion cell and inner plexiform layer (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE) were generated in the central macular subfield. The associations among VA and retinal layer metrics were determined by multivariate linear regressions after adjusting for covariates (age, sex, race, HbA1c, diabetes type, and duration) and correcting for multiple comparisons. Results In DME subjects, increased GCLIPL and OPL thickness and decreased OSL thickness were associated with reduced VA. Furthermore, increased NFL reflectance and decreased OSL reflectance were associated with reduced VA. Additionally, increased areas of INL and ONL interface disruptions were associated with reduced VA. In subjects without DME, increased INL thickness was associated with reduced VA, whereas in subjects without DME but with previous antivascular endothelium growth factor treatment, thickening of OPL was associated with reduced VA. Conclusions Alterations in retinal layer thickness and reflectance metrics derived from enface OCT images were associated with reduced VA with and without presence of DME, suggestive of their potential for monitoring development, progression, and treatment of DME.

Lipid-derived and other oxidative modifications of retinal proteins in a rat model of Smith-Lemli-Opitz syndrome

Oxidative modification of proteins can perturb their structure and function, often compromising cellular viability. Such modifications include lipid-derived adducts (e.g., 4-hydroxynonenal (HNE) and carboxyethylpyrrole (CEP)) as well as nitrotyrosine (NTyr). We compared the retinal proteome and levels of such modifications in the AY9944-treated rat model of Smith-Lemli-Opitz syndrome (SLOS), in comparison to age-matched controls. Retinas harvested at 3 months of age were either subjected to proteomic analysis or to immuno-slot blot analysis, the latter probing blots with antibodies raised against HNE, CEP, and NTyr, followed by quantitative densitometry. HNE modification of retinal proteins was markedly (>9-fold) higher in AY9944-treated rats compared to controls, whereas CEP modification was only modestly (≤2-fold) greater, and NTyr modification was minimal and exhibited no difference as a function of AY9944 treatment. Anti-HNE immunoreactivity was greatest in the plexiform and ganglion cell layers, but also present in the RPE, choroid, and photoreceptor outer segment layer in AY9944-treated rats; control retinas showed minimal HNE labeling. 1D-PAGE/Western blot analysis of rod outer segment (ROS) membranes revealed HNE modification of both opsin and β-transducin. Proteomic analysis revealed the differential expression of several retinal proteins as a consequence of AY9944 treatment. Upregulated proteins included those involved in chaperone/protein folding, oxidative and cellular stress responses, transcriptional regulation, and energy production. βA3/A1 Crystallin, which has a role in regulation of lysosomal acidification, was down-regulated. Hence, oxidative modification of retinal proteins occurs in the SLOS rat model, in addition to the previously described oxidation of lipids. The results are discussed in the context of the histological and physiological changes that occur in the retina in the SLOS rat model.