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Background/Objectives: Retinal hyperreflective foci, 25–50 µm in diameter, that can be imaged by noninvasive optical coherence tomography (OCT) may represent microglial activity related to inflammation. This study aimed to detect hyperreflective foci in the OCT-hyporeflective avascular outer nuclear layer of the retina in relapsing–remitting MS (RRMS) patients without ongoing eye or optic nerve disease. Methods: A cohort of 13 RRMS patients (8 eyes with and 18 eyes without prior optic neuritis) underwent retinal OCT at baseline, after 1 month, after 6 months, and then every 6 months for 3 years. The data were compared with single-examination data from 106 eyes in 53 age-matched healthy subjects. Results: The prevalence of hyperreflective foci at baseline was higher in RRMS patients than in healthy subjects (46.2% vs. 1.8%, p < 0.005). Patients with optic neuritis had much more foci than those without (p < 0.001). Hyperreflective foci recurred in 23.1% of RRMS patients, bilaterally in one with prior optic neuritis and unilaterally in two without. Conclusions: Patients with RRMS, notably those with prior optic neuritis, had elevated rates of retinal infiltration in the absence of retinal disease, suggesting that the phenomenon may represent elevated activity of an immune surveillance or housekeeping mechanism rather than retinal disease. [ABSTRACT FROM AUTHOR]

Purpose: To describe the optical coherence tomography (OCT) findings of hyper-reflective outer nuclear layer (HONL) in two cases of stromal choroiditis (Vogt--Koyanagi--Harada disease -- VKH, and sympathetic ophthalmia -- SO). Methods: Case report Results: Clinical and imaging findings of two patients (37-year-old female with VKH and 34-year-old male with SO) have been described. Both patients showed typical features of the disease with subretinal fluid accumulation and choroidal thickening on OCT. However, OCT of both patients at the initial visit revealed HONL, which was unusual in these conditions. During follow-up, OCT scans revealed thinning and atrophy of the outer retinal layers, irregular thickening of the retinal pigment epithelium, and irregular autofluorescence pattern on autofluorescence imaging. Conclusions: The presence of HONL may serve as a poor prognostic factor in VKH and SO, resulting in thinning and atrophy of the outer retinal layers. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the changes in macular structures following subthreshold micropulse laser (SHML) treatment for chronic central serous chorioretinopathy (cCSC). Methods: Data of 33 eyes from 31 cCSC patients treated with SHML and followed up for at least 6 months has been included in this retrospective study. Main outcome measurements include resolution of subretinal fluid (SRF) and pigment epithelial detachment (PED), the recovery of ellipsoid zone (EZ) continuity, and the foveal outer nuclear layer (ONL) thickness along with its ratio. Results: Mean observation period is 7.355 months (ranging from 6 to 24 months) and mean number of treatments administered is 1.839 (ranging from 1 to 5). 6 months after SHML treatment, there is a significant decrease in the area of SRF and PED (P < 0.001, P = 0.010, respectively). Additionally, the frequency of continuous EZ and the foveal ONL thickness reveal a significant increase (P<0.001, P = 0.005, respectively). The ratio of foveal ONL thickness is significantly higher after laser treatment, particularly in patients with a disease duration of ≤12 months (p = 0.022, P=0.036, respectively). Conclusion: SHML treatment proves to be effective in cCSC eyes, leading to satisfactory recovery of macular structures, especially the photoreceptor layer. [ABSTRACT FROM AUTHOR]

Introduction: With advancements in imaging technology, researchers have been able to identify more distinctive imaging features of central serous chorioretinopathy (CSC). However, existing research primarily concentrates on young patients aged 50 years and below, leaving a dearth of studies on elderly CSC patients. Previous studies indicate that elderly CSC patients may exhibit unique imaging characteristics and have a clinical prognosis that significantly differs from younger patients. This study aimed to evaluate the characteristics of retina, choroid structure, and blood flow in elderly patients with chronic CSC (cCSC) examined multimode imaging and try to find new pathogenesis information of it. Methods: Using a cut-off age of 50 years, patients with chronic central serous chorioretinopathy were divided into two groups: older and younger. The control group consisted of 40 healthy individuals, with their right eyes assigned. Various clinical features were recorded, including the incidence of ellipsoid zone rupture (EZ-), fibrin in the subretinal fluid (SRF), pachydrusen, subretinal drusenoid deposits (SDD), pigment epithelial detachment (PED), double-layer sign (DLS), and choroidal lipid globule cavern. Measurements were taken for the thickness of the outer nuclear layer (ONL), the length of the extended outer photoreceptor segment (POS), the height and width of SRF, the vascular density of each layer of the retinal capillary plexus, the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT). Results: The proportion of females in the elderly group (43.75%) was significantly higher than that in the youth group (22.41%) (p = 0.034). The degree of hyperopia in the elderly group (1.03 ± 0.73) was higher than that in the youth group (0.26 ± 1.06), with a significant difference in BCVA (p = 0.05). The thickness of SFCT, CMT, ONL in the elderly group, and the length of photoreceptor outer segment in the elderly group were thinner than those in the youth group (p < 0.05). Choroidal capillary perfusion area (CCPA), macular area, and paramacular area were lower in the elderly group than those in the youth group in the full scan range (p < 0.05). The blood flow densities of deep capillary plexus (DCP), intermediate capillary plexus (ICP), and superficial capillary plexus (SCP) in the whole scan range, macular area, and paramacular area were lower in the elderly group than in the youth group, but the differences were not statistically significant. Conclusions: In conclusion, our data suggest that elderly patients with cCSC may experience different disease outcomes. Elderly cCSC patients exhibit less gender bias, poorer vision, more severe structural damage and ischemia in the choroid and retina, and have a higher risk of developing choroidal neovascularization. [ABSTRACT FROM AUTHOR]

Abstract Introduction With advancements in imaging technology, researchers have been able to identify more distinctive imaging features of central serous chorioretinopathy (CSC). However, existing research primarily concentrates on young patients aged 50 years and below, leaving a dearth of studies on elderly CSC patients. Previous studies indicate that elderly CSC patients may exhibit unique imaging characteristics and have a clinical prognosis that significantly differs from younger patients. This study aimed to evaluate the characteristics of retina, choroid structure, and blood flow in elderly patients with chronic CSC (cCSC) examined multimode imaging and try to find new pathogenesis information of it. Methods Using a cut-off age of 50 years, patients with chronic central serous chorioretinopathy were divided into two groups: older and younger. The control group consisted of 40 healthy individuals, with their right eyes assigned. Various clinical features were recorded, including the incidence of ellipsoid zone rupture (EZ-), fibrin in the subretinal fluid (SRF), pachydrusen, subretinal drusenoid deposits (SDD), pigment epithelial detachment (PED), double-layer sign (DLS), and choroidal lipid globule cavern. Measurements were taken for the thickness of the outer nuclear layer (ONL), the length of the extended outer photoreceptor segment (POS), the height and width of SRF, the vascular density of each layer of the retinal capillary plexus, the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT). Results The proportion of females in the elderly group (43.75%) was significantly higher than that in the youth group (22.41%) (p = 0.034). The degree of hyperopia in the elderly group (1.03 ± 0.73) was higher than that in the youth group (0.26 ± 1.06), with a significant difference in BCVA (p = 0.05). The thickness of SFCT, CMT, ONL in the elderly group, and the length of photoreceptor outer segment in the elderly group were thinner than those in the youth group (p

INTRODUCTION: We investigated the correlation between retinal thickness and optic tract integrity in subjects with autosomal dominant Alzheimer's disease (ADAD) causing mutations. METHODS: Retinal thicknesses and diffusion tensor images (DTI) were obtained using optical coherence tomography and magnetic resonance imaging, respectively. The association between retinal thickness and DTI measures was adjusted for age, sex, retinotopy, and correlation between eyes. RESULTS: Optic tract mean diffusivity and axial diffusivity were negatively correlated with retinotopically defined ganglion cell inner plexiform thickness (GCIPL). Fractional anisotropy was negatively correlated with retinotopically defined retinal nerve fiber layer thickness. There was no correlation between outer nuclear layer (ONL) thickness and any DTI measure. DISCUSSION: In ADAD, GCIPL thickness is significantly associated with retinotopic optic tract DTI measures even in minimally symptomatic subjects. Similar associations were not present with ONL thickness or when ignoring retinotopy. We provide in vivo evidence for optic tract changes resulting from ganglion cell pathology in ADAD. [ABSTRACT FROM AUTHOR]

IntroductionCongenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS.MethodsMedical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene.ResultsOCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene.ConclusionIn XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy (occult retinoschisis). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis.

Photoreceptor transplant has been put forward as a repair strategy to tackle degenerated retinas. Nonetheless, cell death and immune rejection seriously limit the success of this strategy, with only a small fraction of transplanted cells surviving. Improving the survival of transplanted cells is of critical importance. Recent evidence has identified receptor‐interacting protein kinase 3 (RIPK3) as a molecular trigger controlling necroptotic cell death and inflammation. However, its role in photoreceptor transplantation and regenerative medicine has not been studied. We hypothesized that modulation of RIPK3 to address both cell death and immunity could have advantageous effects on photoreceptor survival. In a model of inherited retinal degeneration, deletion of RIPK3 in donor photoreceptor precursors significantly increases the survival of transplanted cells. Simultaneous RIPK3 deletion in donor photoreceptors and recipients maximizes graft survival. Lastly, to discern the role of RIPK3 in the host immune response, bone marrow transplant experiments demonstrated that peripheral immune cell RIPK3 deficiency is protective for both donor and host photoreceptor survival. Interestingly, this finding is independent of photoreceptor transplantation, as the peripheral protective effect is also observed in an additional retinal detachment photoreceptor degeneration model. Altogether, these results indicate that immunomodulatory and neuroprotective strategies targeting the RIPK3 pathway can aid regenerative therapies of photoreceptor transplantation. [ABSTRACT FROM AUTHOR]

Objective To study the effect of strong visible light on the structure and function of the rat retina and its mechanism. Methods Self-made light box. Adult Sprague-Dawley (SD) rats were randomly divided into normal control and experimental groups. Normal control group rats were raised in a normal environment of 12 h light / 12 h dark cycle. Rats in the experimental group were first darkly adapted for 24 h, then were irradiated with 5 000 lx strong visible light for 48 h, followed by a dark adaption of another 24 h. All the rats were anesthetized for about 30 minutes. Firstly, the retinal function of the rats were detected by retinal electrophysiology (ERG); Secondly, rats' eyeballs were removed and fixed in fixative solution or 4% polyoxymethylene before paraffin or frozen sections were made for HE staining and TUNEL staining respectively. Paraffin sections with HE staining were used to observe the change of retinal tissue structures under light microscope, and frozen sections with TUNEL staining were observed under confocol microscope. qRT-PCR and Western blot (WB) were used to detect tumor necrosis factor-α (TNF-α) content in the photo damaged retinas. Results HE staining showed that retinal outer nuclear layer was significantly thinner than normal after light exposure, and the temporal side was more severely damaged than the nasal side; TUNEL staining showed that the number of retinal apoptotic cells increased significantly after photo damage; qRT-PCR and WB revealed that TNF-α increased in the photo damaged retinas；and ERG demonstrated that the retinal function of photo damaged rats was significantly reduced. All the results above were statistically different（P<0.05）. Conclusions The damage of outer nuclear layer (ONL) after light exposure is one of the reasons for the impairment of retinal function, and the retinal damage may be related to the increased expression of TNF-α. [ABSTRACT FROM AUTHOR]

(1) Background: Tacrolimus is an immunosuppressive agent commonly used in the management of solid organ allogeneic transplants in the prevention of rejection. Serious ophthalmic adverse effects with Tacrolimus have been reported in the literature, which includes cortical blindness and optic neuropathy. (2) Methods: We describe a rare case of maculopathy as a possible complication of Tacrolimus therapy. A 56-year-old man receiving Tacrolimus for immunosuppression after liver transplantation developed unilateral visual disturbance with a central scotoma. (3) Results: Ophthalmologic examination revealed unilateral maculopathy; a Tacrolimus macular toxicity was suspected. After drug discontinuation, a complete visual recovery was observed; however, the ultrastructural macular damage was irreversible. (4) Conclusions: Reports regarding maculopathy associated with Tacrolimus are limited. This case report adds to the current literature regarding the possible macular toxicity of this immunosuppressive agent, especially if it exceeds therapeutic serum levels. Further data are needed to confirm this possible association. A careful ophthalmologic examination should be promptly performed in patients manifesting visual disturbance while taking Tacrolimus to prevent irreversible, permanent vision loss due to possible drug toxicity.

Purpose: To analyze the recovery course of foveal microstructures in eyes with nonsurgical healing of full-thickness macular hole (FTMH). Methods: By serial OCT scans, the temporal healing sequences were analyzed in ocular trauma, vitreomacular traction (VMT), cystoid macular edema (CME), and the remaining group. We evaluated correlations between the final best-corrected spectacle visual acuity and reconstruction time of external limiting membrane (ELM), and inner segment/outer segment (IS/OS). Results: The healing (mean±standard deviation in months) most involved fusion at the level of the outer nuclear layer (ONL) (6.3±10.5) followed by restoration of ELM (9.1±13.8), and lastly, by IS/OS regeneration (13.1±19.5). In severe blunt ocular trauma, healing was fast and involved subretinal zipper glue-like reapposition with resulting outer retinal atrophy. Best spectacle-corrected visual acuity correlated with normalization of the clivus (p=0.012), faster ELM (p=0.006), and IS/OS reconstitution (p=0.024). Recurrence of FTMH occurred when the healing was halted (3 eyes) or was aberrant by lamellar hole epiretinal proliferation (LHEP) (3 eyes) or by the persistence of VMT (1 eye). Conclusion: Recovery sequences proceeded from the ONL to the deeper layers with BCVA correlating absolutely and temporally with the restoration of outer retinal layer integrity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

(1) Background: Tacrolimus is an immunosuppressive agent commonly used in the management of solid organ allogeneic transplants in the prevention of rejection. Serious ophthalmic adverse effects with Tacrolimus have been reported in the literature, which includes cortical blindness and optic neuropathy. (2) Methods: We describe a rare case of maculopathy as a possible complication of Tacrolimus therapy. A 56-year-old man receiving Tacrolimus for immunosuppression after liver transplantation developed unilateral visual disturbance with a central scotoma. (3) Results: Ophthalmologic examination revealed unilateral maculopathy; a Tacrolimus macular toxicity was suspected. After drug discontinuation, a complete visual recovery was observed; however, the ultrastructural macular damage was irreversible. (4) Conclusions: Reports regarding maculopathy associated with Tacrolimus are limited. This case report adds to the current literature regarding the possible macular toxicity of this immunosuppressive agent, especially if it exceeds therapeutic serum levels. Further data are needed to confirm this possible association. A careful ophthalmologic examination should be promptly performed in patients manifesting visual disturbance while taking Tacrolimus to prevent irreversible, permanent vision loss due to possible drug toxicity. [ABSTRACT FROM AUTHOR]

We investigated the etiology of decreased cone-driven vision in a light damage (LD) model of retinal degeneration. To induce slow, moderate degeneration, albino rats underwent low-intensity light exposure for 10 days. Electroretinography was utilized to assess physiologic function of the rod- and cone-driven retinal function in LD and control rats. Immunohistochemistry targeting cone arrestin allowed for quantification of cone density and for comparison of the decline in function. Photoreceptor loss was quantified by outer nuclear layer thickness decreases, as observed by optical coherence tomography and histology. The LD rats showed decreased rod- and cone-driven function with partial recovery 30 days after cessation of light exposure. In addition, LD rats showed decreased cone photoreceptor densities in the central retinal region compared to control rats. Our results demonstrate that the loss of cone-driven visual function induced by light damage is at least partially due to the death of cone photoreceptors. [ABSTRACT FROM AUTHOR]

PurposeSpectral-domain optical coherence tomography (SD-OCT) was used to characterize the retinal phenotype, natural history, and treatment responses in a mouse model of X-linked retinoschisis (Rs1-KO) and to identify new structural markers of AAV8-mediated gene therapy outcome.MethodsOptical coherence tomography scans were performed on wild-type and Rs1-KO mouse retinas between 1 and 12 months of age and on Rs1-KO mice after intravitreal injection of AAV8-scRS/IRBPhRS (AAV8-RS1). Cavities and photoreceptor outer nuclear layer (ONL) thickness were measured, and outer retina reflective band (ORRB) morphology was examined with age and after AAV8-RS1 treatment. Outer retina reflective band morphology was compared to immunohistochemical staining of the outer limiting membrane (OLM) and photoreceptor inner segment (IS) mitochondria and to electron microscopy (EM) images of IS.ResultsRetinal cavity size in Rs1-KO mice increased between 1 and 4 months and decreased thereafter, while ONL thickness declined steadily, comparable to previous histologic studies. Wild-type retina had four ORRBs. In Rs1-KO, ORRB1was fragmented from 1 month, but was normal after 8 months; ORRB2 and ORRB3 were merged at all ages. Outer retina reflective band morphology returned to normal after AAV-RS1 therapy, paralleling the recovery of the OLM and IS mitochondria as indicated by anti-β-catenin and anti-COX4 labeling, respectively, and EM.ConclusionsSpectral-domain OCT is a sensitive, noninvasive tool to monitor subtle changes in retinal morphology, disease progression, and effects of therapies in mouse models. The ORRBs may be useful to assess the outcome of gene therapy in the treatment of X-linked retinoschisis patients.

PurposeDirectional Optical Coherence Tomography (D-OCT) is a method used to optically segment and identify the outer nuclear layer (ONL) in vivo. The purpose of this study was to determine the repeatability and reproducibility of D-OCT ONL thickness measurements in healthy eyes.MethodsSixteen healthy eyes of sixteen subjects were imaged using the Cirrus SD-OCT. The OCT beam entry position was varied horizontally and vertically through the pupil, and cross-sectional images were obtained at baseline and 1-month follow-up by two observers. Detailed segmentation was performed to quantify the thickness of ONL without the inclusion of overlying Henle Fiber Layer. Inter-observer, intra-observer, and inter-visit variability was evaluated using Bland-Altman and coefficient of variation analysis for each category.ResultsAll 16 eyes were successfully imaged, registered, and segmented. The maximum mean (SD) inter-operator difference was 2.6 (4.8) μm. The maximum mean (SD) intra-operator difference was 2.4 (5.3) μm. There was no statistically significant difference in ONL measurements detected between baseline and follow-up (p > 0.05). The mean (SD) differences measured across visits by one operator varied from -1.6 (3.1) to 1.1 (6.1) μm. The mean (SD) coefficient of variance (CV%) for all sectors with horizontal orientation was 9.1% (2.3%), 10.1% (2.5%), and 8.6% (2.3%) for inter-observer, intra-observer, and inter-visit, respectively. The mean (SD) coefficient of variance (CV%) for all sectors with vertical orientation was 8.3% (1.8%), 6.9% (1.4%), and 8.3% (2.1%) for inter-observer, intra-observer, and inter-visit, respectively. The majority of the variation of paired repeated measurements originated from between-subject variance. The within-subject variance accounted for less than 1% of the total variability.ConclusionsONL thickness measurements can be quantified with good repeatability and reproducibility using D-OCT. Identifying the magnitude of D-OCT variability among normal subjects will allow for improved development of future clinical studies that quantitatively track the progression of macular pathology.

Objective:To investigate the association between foveal outer nuclear layer (ONL) thickness and the natural course of central serous chorioretinopathy (CSC), as well as the thickness change after photodynamic therapy (PDT), exploring the PDT timing for CSC.Methods:This retrospective consecutive case series included 358 CSC patients between January 2014 and December 2019. All patients were divided into four groups depending on disease duration: Group A: ≤1 month; Group B: >1 and ≤3 months; Group C: >3 and≤6 months and Group D: >6 months. Foveal ONL thickness of the CSC eye and the clinically healthy fellow eye were measured and compared in all patients. Fifty-six patients were successfully treated with half-dose of PDT, showing complete subretinal fluid absorption, were followed up for more than 6 months and further investigated. The recovery of foveal ONL thickness was analyzed in the affected eyes of patients with different disease duration.Results:No significant reduction was found in CSC foveal ONL thickness (μm) compared to the fellow eye in patients with disease duration less than 1 week (112.3 ± 12.2 vs. 116.7 ± 15.3, P = 0.268). Patients with longer disease duration had varying degrees of ONL thinning compared to the contralateral eye (all P < 0.05) and this difference was more pronounced in patients with disease duration greater than 6 months (75.8 ± 12.9 vs. 113.0 ± 11.5, P < 0.001). At 6-month follow-up after PDT, foveal ONL thickness of patients with 1 and≤3 months recovered significantly (88.5 ± 11.5 to 95.8 ± 11.3, P = 0.012) but remained thinner than that of the healthy fellow eye. Foveal ONL thickness did not improve significantly in cases with disease duration longer than 3 months (P > 0.05).Conclusion:Foveal ONL thinning was positively associated with disease duration prior to treatment suggesting that longer disease duration limits scope for foveal ONL recovery. CSC patients should be treated with PDT as soon as possible to prevent disease development and reduced visual function.

Danon disease is a rare, X-linked dominant, lysosomal storage disease characterized by triad muscle weakness, cardiomyopathy, and intellectual disability. To the best of our knowledge, we firstly report outer retinal abnormalities evaluated using high-resolution imaging modalities in a patient with Danon disease. Purpose: To report outer retinal abnormalities evaluated using high-resolution imaging modalities in a patient with Danon disease. Methods: Case report. Results: A 26-year-old woman, diagnosed with Danon disease based on genetic testing, was referred to our department for further evaluation of ocular findings. Her best-corrected VA was 20/20, and color vision was normal. Fundus examination revealed pigmentary changes consisting of mottled depigmentation and pigmentation in the peripheral retina of both eyes. Spectral-domain optical coherence tomography revealed disruptions of the ellipsoid and interdigitation zones, irregularity of the retinal pigment epithelium, and hyperreflectivity of the outer nuclear layer. In addition, an adaptive optics retinal camera demonstrated the ambiguous macular cone mosaic pattern. Conclusion: Danon disease is caused by a primary deficiency in lysosomal associated membrane protein 2, an important constituent of the lysosomal membrane that plays a crucial role in the process of autophagy. It is possible that the findings of spectral-domain optical coherence tomography and adaptive optics retinal camera are early changes associated with the accumulation of autophagosomes and/or phagosomes due to lysosomal associated membrane protein 2 dysfunction in the photoreceptors, eventually followed by outer retinal degeneration, such as thinning of both the photoreceptor and retinal pigment epithelium layers at the fovea. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate tangential morphological changes in the outer retina and assess their correlation with the degree of metamorphopsia in patients with idiopathic epiretinal membrane (ERM). Methods: This retrospective study included patients with idiopathic ERM who underwent vitrectomy between January 2018 and December 2019. We evaluated the preoperative examination results. Using cross-sectional spectral-domain optical coherence tomography (OCT) images along the horizontal/vertical meridian through the fovea, we defined a new parameter, tangential displacement (TD), as the tangential component of the position vector of the distorted outer nuclear layer caused by ERM. Visual function measurements included M-CHARTS results (vertical/horizontal metamorphopsia score [MV/MH]) and best-corrected visual acuity (BCVA). The correlations among the OCT parameters including TD and central foveal thickness (CFT) with visual function measurements were determined. Results: Overall, 78 eyes of 76 patients (49 females; mean age, 67.9 [± standard deviation, 7.5 years]) were included. The mean horizontal TD was 24.0 ± 73.9 μm, which was significantly different from 0 (p = 0.005). The mean vertical TD was 6.0 ± 76.2 μm, which was not significantly different from 0. The absolute value of horizontal TD was significantly correlated with MV (r = 0.513, p < 0.01) and MH (r = 0.423, p < 0.01). The absolute value of vertical TD was also significantly correlated with MV (r = 0.274, p = 0.02) and MH (r = 0.413, p < 0.01). However, neither value was significantly correlated with BCVA. Multiple regression analysis showed that the horizontal absolute TD was an independent factor associated with both MV (β = 0.635, p < 0.001) and MH (β = 0.259, p = 0.048). Conclusion: We found that ERM tended to distort the outer retinal layer toward the temporal side of the fovea. The tangential distortion of this layer was associated with the degree of metamorphopsia, suggesting that misalignment of parafoveal photoreceptors causes metamorphopsia in patients with ERM. [ABSTRACT FROM AUTHOR]

Quantification of retinal atrophy, caused by therapeutics and/or light, by manual measurement of retinal layers is labor intensive and time-consuming. In this study, we explored the role of deep learning (DL) in automating the assessment of retinal atrophy, particularly of the outer and inner nuclear layers, in rats. Herein, we report our experience creating and employing a hybrid approach, which combines conventional image processing and DL to quantify rodent retinal atrophy. Utilizing a DL approach based upon the VGG16 model architecture, models were trained, tested, and validated using 10,746 image patches scanned from whole slide images (WSIs) of hematoxylin-eosin stained rodent retina. The accuracy of this computational method was validated using pathologist annotated WSIs throughout and used to separately quantify the thickness of the outer and inner nuclear layers of the retina. Our results show that DL can facilitate the evaluation of therapeutic and/or light-induced atrophy, particularly of the outer retina, efficiently in rodents. In addition, this study provides a template which can be used to train, validate, and analyze the results of toxicologic pathology DL models across different animal species used in preclinical efficacy and safety studies. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to investigate the deformation of the outer nuclear layer using optical coherence tomography in patients with epiretinal membrane (ERM) and its relationship with metamorphopsia. Methods Thirty-nine eyes from 39 patients with ERM were included in the study. Patients with the subtypes of pseudo macula hole and lamellar hole were excluded. Twenty-one fellow eyes without macular disease were included as normal controls. Forty-nine B-scan images were obtained in the range of 20 degrees around the macula using SD-OCT. The outer nuclear layer (ONL) was evaluated as a three-dimensional image (3D-ONL) reconstructed using the distance between the ONL and retinal pigment epithelium (RPE) line. The deformation of the ONL was figured at the reference plane and evaluation plane (ONL-B). The characteristic parameters of the ONL-B were defined as circularity, area ratio, and axis ratio. The correlations between these parameters and visual acuity and MCHART score ratio (MH/MV) were then evaluated. Results ONL height was significantly higher in ERM patients than in normal controls (54.1 ± 5.3 μm and 84.1 ± 12.9 μm, respectively; P

Abstract Background To investigate the relationship between the foveal outer nuclear layer (ONL) thickness in the active and resolved phases of central serous chorioretinopathy (CSC), and its possible association with optical coherence tomography (OCT) parameters. Methods The medical records of CSC patients treated with half-dose photodynamic therapy (PDT) between August 2011 and October 2017 were reviewed. The difference between the foveal ONL thickness at 12 m after half-dose PDT and that before half-dose PDT was analyzed, and its association with OCT parameters was assessed using generalized linear models. Results Sixty-two patients were included. The mean difference in foveal ONL thickness was 9.15 ± 8.16 μm. The average ratios of the retinal detachment height to the subretinal space width on horizontal and vertical scans were 0.10 ± 0.04 and 0.12 ± 0.04, respectively. The ratio was independently associated with the degree of increase in the foveal ONL thickness difference on both the horizontal scans (β = 103.684, P = .000) and vertical scans (β = 67.569, P = .000), even after adjusting for potential confounders. Conclusions The majority of resolved CSC eyes showed some increase in foveal ONL thickness, and the degree of increase was related to the ratio of the retinal detachment height to the subretinal space width in their active phase. It suggested that the retina is stretched when it becomes detached, and recovers with resolution of the subretinal fluid. Therefore, besides photoreceptor cell death, retinal stretch may contribute to the reduction in foveal ONL thickness in eyes with active CSC.

We investigated the etiology of decreased cone-driven vision in a light damage (LD) model of retinal degeneration. To induce slow, moderate degeneration, albino rats underwent low-intensity light exposure for 10 days. Electroretinography was utilized to assess physiologic function of the rod- and cone-driven retinal function in LD and control rats. Immunohistochemistry targeting cone arrestin allowed for quantification of cone density and for comparison of the decline in function. Photoreceptor loss was quantified by outer nuclear layer thickness decreases, as observed by optical coherence tomography and histology. The LD rats showed decreased rod- and cone-driven function with partial recovery 30 days after cessation of light exposure. In addition, LD rats showed decreased cone photoreceptor densities in the central retinal region compared to control rats. Our results demonstrate that the loss of cone-driven visual function induced by light damage is at least partially due to the death of cone photoreceptors.

The effects of visible light, from short to long wavelengths, on the retina were investigated functionally and histologically. The left eyes of Sprague–Dawley albino rats (6-weeks old, n = 6 for each wavelength) were exposed to seven narrow-band wavelengths (central wavelengths, 421, 441, 459, 501, 541, 581, and 615 nm) with bandwidths of 16 to 29 nm (half bandwidth, ±8–14.5 nm) using a xenon lamp source with bandpass filters at the retinal radiant exposures of 340 and 680 J/cm2. The right unexposed eyes served as controls. Seven days after exposure, flash electroretinograms (ERGs) were recorded, and the outer nuclear layer (ONL) thickness was measured. Compared to the unexposed eyes, significant reductions in the a- and b-wave ERG amplitudes were seen in eyes exposed to 460-nm or shorter wavelengths of light. The ONL thickness near the optic nerve head also tended to decrease with exposure to shorter wavelengths. The decreased ERG amplitudes and ONL thicknesses were most prominent in eyes exposed to 420-nm light at both radiant exposures. When the wavelengths were the same, the higher the amount of radiant exposure and the stronger the damage. Compared to the unexposed eyes, the a- and b-waves did not decrease significantly in eyes exposed to 500-nm or longer wavelength light. The results indicate that the retinal damage induced by visible light observed in albino rats depends on the wavelength and energy level of the exposed light.

AIM: To compare the outer nuclear layer(ONL), inner and outer segments(IS/OS), photoreceptor cell layer in healthy people and diabetic retinopathy by frequency-domain optical coherence tomography(OCT). METHODS: Totally 100 eyes of 50 healthy people were selected as control group. According to conventional mydriasis for examination of fundus and fundus fluorescein angiography(FFA)examination, all diabetic cases were divided into 3 groups: normal retina group(NDR), non-proliferative diabetic retinopathy group(NPDR), proliferative diabetic retinopathy group(PDR). Using OCT measure the thickness of ONL, IS/OS and photoreceptor cell layer of fovea and parafovea(nasal side and temporal side)in the four groups. RESULTS: Compared with the control group, the ONL and photoreceptor cell layer's thickness of macular fovea and temporal parafovea in NPDR group and PDR group were statistically significant(all PP>0.05). The IS/OS of macular fovea and temporal parafovea was not significantly different among those groups(P>0.05). The thickness of different layers of nasal parafovea were not different(P>0.05).CONCLUSION: The thickness of macular fovea and temporal parafovea has relation with degree of DR; the change of photoreceptor cell layer's thickness occurs mainly in ONL, but IS/OS no change; the change in temporal parafovea more obvious than in nasal parafovea. Frequency-domain OCT can quantitatively and qualitatively observe the subtle diabetic macular changes in diabetic patients with macular disease, and provides a reliable detection for the early diagnosis and treatment.

Background: Drusen are seen in the early and intermediate stages of age-related macular degeneration. A retrospective, two-year observational study at a tertiary centre was designed to assess outer nuclear layer thickness in different types of drusen.Methods: Patients over 50 years of age with predominant soft drusen or reticular pseudodrusen were included in the study. Fundus photography, infrared, fundus autofluorescence and spectral domain optical coherence tomography were performed at baseline, years one and two. Outer nuclear layer thickness was measured in the nine Early Treatment Diabetic Retinopathy Study subfields, and the rate of thinning was determined using generalised estimating equations models.Results: Data were analysed from 17 eyes with soft drusen and nine eyes with reticular pseudodrusen. Greater outer nuclear layer thinning was seen overall and in all subfields in reticular pseudodrusen as compared to soft drusen, with statistically significant differences found mostly in superior and nasal subfields of ring 2. The outer nuclear layer was 5-12 μm thinner in eyes with reticular pseudodrusen, and the rate of thinning was greater in eyes with reticular pseudodrusen in the outer superior subfield.Conclusions: Outer nuclear layer thickness is consistently lower in patients with reticular pseudodrusen compared with soft drusen, irrespective of subfield location. These structural findings may contribute to explain the functional abnormalities observed in patients with reticular pseudodrusen. [ABSTRACT FROM AUTHOR]

Purpose: To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs with sudden acquired retinal degeneration syndrome (SARDS). Methods: Retinal OCT was performed on 10 SARDS dogs and eight control dogs. Tomograms were collected in four quadrants around the optic nerve. Measurements were collected from the photoreceptor layer, the outer nuclear layer, the outer retina, the inner retina and the whole retina thickness in all quadrants. Sodium fluorescein was injected intravenously and serial fundic photographs were collected for a 5 minute period post‐injection. Results: In all quadrants, the outer nuclear layer (dorsal temporal P = 0.0000, dorsal nasal P = 0.0001, ventral temporal P = 0.0002, ventral nasal P = 0.000) and outer retina (dorsal temporal P = 0.0001, dorsal nasal P = 0.0002, ventral temporal P = 0.0054, ventral nasal P = 0.0084) measurements were significantly decreased in SARDS dogs. The whole retina thickness was significantly decreased in the dorsal temporal (P = 0.0082) and ventral temporal (P = 0.0428) retina. There were no significant differences in the photoreceptor layer thickness or inner retinal thickness between SARDS and control dogs. All SARDS dogs had a loss of definition of all of the photoreceptor bands on OCT. Two SARDS dogs had multifocal small retinal detachments and one of these dogs exhibited fluorescein leaking at the detachment sites. Conclusions: The significant reduction in the outer nuclear layer and the loss of band signals in the photoreceptor layers in dogs with SARDS identified on OCT support the previous histopathology findings. Small detachments may occasionally be detected on OCT and they may leak fluorescein. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a relation between the outer nuclear layer (ONL) thickness and symptom duration in patients with central serous chorioretinopathy (CSC) using spectraldomain optical coherence tomography (SDOCT) and to compare with healthy subjects. Methods: This retrospective study included 67 CSC patients and 20 healthy subjects. The ONL thickness was measured between internal limiting membrane and external limiting membrane at central fovea using SD-OCT (Topcon 3D OCT-2000, Japan). The patients were divided into six groups based on symptom duration: group (1) contained 14 patients (symptom duration between 1 and 30 days) , group (2) contained 11 patients (symptom duration between 31 and 60 days), group (3) contained 12 patients (symptom duration between 61 and 90 days) , group (4) contained 11 (symptom duration between 91 and 120 days), group (5) contained 7 patients (symptom duration between 121 and 150 days) and group (6) contained 12 (symptom duration between 151 days and more). Results: The average ONL thickness was 76.1 ± 16.8 μm in CSC in all patients and 122.4 ± 2.8 μm in healthy subjects. The major differences were between group (3) and (4) (p < 0.001). The ONL thickness was negatively correlated with symptom duration (rs = − 0.918; p< 0.001). In addition, the ONL thickness was positively correlated with BCVA (rs = 0.619; p< 0.001). Conclusion: Photoreceptor loss could begin within the first 3 months in CSC. [ABSTRACT FROM AUTHOR]

Abstract We have previously demonstrated that a reduction in ubiquitin (Ub) levels via disruption of the polyubiquitin gene Ubb results in reactive gliosis and hypothalamic neurodegeneration in mice. However, it is not known whether other neural tissues, apart from the brain, can also be affected by Ubb disruption. We examined the retina, which, being derived from the diencephalon, has the same developmental origin as the hypothalamus. We found that expression levels of Ubb were much higher than those of the other polyubiquitin gene Ubc in the retina. In retinal tissues from Ubb knockout (KO) mice, we found that Ubc expression was upregulated to compensate for the loss of Ubb ; however, the Ub pool remained disrupted, with reduced levels of free Ub. To directly demonstrate whether the disrupted Ub pools affect neural integrity in retinal tissues, we investigated retinal layers in control and Ubb KO mice. Using optical coherence tomography and histological analysis, we demonstrated that the thickness of the outer nuclear layer of the retina was decreased in Ubb KO mice compared to control mice, suggesting that retinal degeneration was induced by Ub deficiency. Furthermore, the mRNA and protein levels of rhodopsin decreased and those of glial fibrillary acidic protein increased in Ubb KO mouse retinas. Therefore, the maintenance of Ub pools in the retina appears to be crucial for the survival of photoreceptor cells and the prevention of excessive glial cell activation. Highlights • Ub pools fluctuated due to reduced levels of free Ub in the retinas of Ubb KO mice. • A compensatory upregulation of Ubc was observed in the retinas of Ubb KO mice. • Degeneration of the ONL occurred in an age-dependent manner in Ubb KO retinas. • Altered expression levels of rhodopsin and GFAP were observed in Ubb KO retinas. • Overt signs of photoreceptor layer degeneration were observed in adult Ubb KO mice. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the deformation of the outer nuclear layer using optical coherence tomography in patients with epiretinal membrane (ERM) and its relationship with metamorphopsia.Methods: Thirty-nine eyes from 39 patients with ERM were included in the study. Patients with the subtypes of pseudo macula hole and lamellar hole were excluded. Twenty-one fellow eyes without macular disease were included as normal controls. Forty-nine B-scan images were obtained in the range of 20 degrees around the macula using SD-OCT. The outer nuclear layer (ONL) was evaluated as a three-dimensional image (3D-ONL) reconstructed using the distance between the ONL and retinal pigment epithelium (RPE) line. The deformation of the ONL was figured at the reference plane and evaluation plane (ONL-B). The characteristic parameters of the ONL-B were defined as circularity, area ratio, and axis ratio. The correlations between these parameters and visual acuity and MCHART score ratio (MH/MV) were then evaluated.Results: ONL height was significantly higher in ERM patients than in normal controls (54.1 ± 5.3 μm and 84.1 ± 12.9 μm, respectively; P < 0.001). In ERM patients, the MV score was 0.53 ± 0.50, the MH score was 0.71 ± 0.61, and the distance from the RPE line to the ONL-B was 153.5 ± 13.5 μm. The axis of the ONL-B in normal controls and ERM patients was - 6.25 ± 21.8 and - 1.28 ± 29.1, respectively, which indicates that the ONL is horizontally long in both normal individuals and ERM patients. The circularity and area ratio were significantly smaller in ERM patients than in normal controls. In all ERM patients, MH/MV had a significant correlation with axis (r = - 0.29, p = 0.034), circularity (r = - 0.28, p = 0.044), and area ratio (r = - 0.47, p = 0.001). Moreover, we found that the correlation was more significant if the subjects had an axis of the ONL within ±10 degrees (n = 16); the correlations of MH/MV with axis (r = - 0.29, p = 0.034), circularity (r = - 0.53, p = 0.021), and area ratio were more significant (r = - 0.78, P < 0.0001).Conclusion: The ONL is horizontally long in normal individuals and ERM patients. The direction of metamorphopsia is correlated with the direction of ONL deformation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the integrity of the outer retinal layers—outer nuclear layer (ONL), external limiting membrane (ELM), ellipsoid (EZ), and interdigitation band (IZ)—using spectral-domain optical coherence tomography and estimate their effect on visual acuity in retinitis pigmentosa (RP).Methods: A cross-sectional study was performed in the Ophthalmology Department of Hospital de Braga, Portugal. Patients with RP followed in the Hospital de Braga during January to August 2017 were included. Exclusion criteria were lack of data, macular edema due to RP, and concomitant retinal, optic nerve, or corneal disease that could interfere with visual acuity. Age, sex, time from diagnosis, phakic status, ONL thickness, and presence or absence of foveal ELM, EZ, and IZ were correlated to the best-corrected visual acuity (BCVA).Results: Forty-eight eyes were analyzed. There was a strong and positive correlation in BCVA between both eyes (p < .001*). ONL thickness was decreased in 95.8%. The EZ was the most absent layer (79.2%), followed by IZ (70.8%) and ELM (45.8%). A positive family history (p = .04*) and increased time from diagnosis (p = .037*) correlated with worse BCVA. A thicker ONL (p = .001*) and the presence of subfoveal ELM (p < .001*), EZ (p < .001*), and IZ (p = .02*) are correlated with better BCVA. There was a strong and positive correlation between the number of layers affected and a lower BCVA (p < .001). The presence of EZ was a significant predictor of BCVA (p = .02*).Conclusions: The status of the outer retinal layers seems to influence BCVA. The status of the EZ was the most important predictor of BCVA but the ONL, ELM, and IZ may have a cumulative effect in the progression of visual loss. [ABSTRACT FROM AUTHOR]

In hydroxychloroquine (HCQ) retinopathy, early detection of asymptomatic retinal changes and the interruption of the drug are essential to prevent permanent vision loss. Our purpose was to investigate the roles of ganglion cell layer (GCL) and outer nuclear layer (ONL) thicknesses measured by optical coherence tomography (OCT) in the early diagnosis of retinopathy. One hundred and fourteen eyes of 76 individuals with HCQ treatment were enrolled in the study (42 eyes with impaired visual field (VF) and 72 eyes with nondamaged VF). We found that ONL was significantly decreased in the HCQ retinopathy group compared with the control group in the nasal macula (p = 0.032) as well as in four sectors (p < 0.044), whereas no significant differences were found comparing GCL in both groups. If VF were altered superiorly or temporarily, ONL was significantly thinned inferiorly (p = 0.029) and nasally (p = 0.008), respectively. Duration of HCQ treatment was significantly related with ONL in seven sectors of ONL (p < 0.047). We suggest that ONL measured with OCT might be used to assess early HCQ retinal toxicity.