TOWARD AN IMAGING-CENTRIC DEFINITION OF NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY.

PURPOSE: To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria. METHODS: This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease. RESULTS: Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone. CONCLUSION: Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.

CHOROIDAL AND RETINAL ABNORMALITIES IN CUSHING SYNDROME: Correlation with the Cortisol Level.

PURPOSE: To investigate the structure and blood flow of the retina and choroid in Cushing syndrome and their relationship with cortisol levels. METHODS: A consecutive series of patients with Cushing syndrome with adrenocortical carcinoma were included in this study. Cortisol levels gradually returned to normal after adrenalectomy. Optical coherence tomography and optical coherence tomography angiography were used to assess patients with Cushing syndrome before and after the surgery for retina and choroid. Correlation analysis was performed between cortisol level and fundus changes. RESULTS: Compared with normal cortisol levels, patients with Cushing syndrome had significantly lower central macular thickness with increased cortisol level (220.82 ± 16.59 µ m and 223.68 ± 15.78 µ m, P = 0.019). However, the central choroidal thickness was higher with increased cortisol level (255.18 ± 105.89 µ m and 205.94 ± 87.04 µ m, P < 0.001). The choriocapillaris flow area was higher with increased cortisol level (2.05 ± 0.14 mm 2 and 2.00 ± 0.13 mm 2 , P = 0.02). The change of choriocapillaris flow area was correlated with the score of Huaxi Emotional-distress Index and 24-hour urine-free cortisol (24h-UFC). CONCLUSION: The increased cortisol level was correlated with lesser central macular thickness and thicker central choroidal thickness. The decrease of choriocapillaris flow area was correlated with 24h-UFC, indicating the effect of increased cortisol level on choroidal vessels.

Analysis of Radial Peripapillary Capillary Density in Patients with Bietti Crystalline Dystrophy by Optical Coherence Tomography Angiography.

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION: The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.

CHARACTERISTICS AND MANAGEMENT OF MYOPIC TRACTION MACULOPATHY IN MYOPIC EYES WITH AXIAL LENGTH LESS THAN 26.5 mm.

PURPOSE: To explore the characteristics and underlying mechanisms of myopic traction maculopathy (MTM) with axial length less than 26.5 mm and to assess the effectiveness of macular buckling for the treatment of MTM. METHODS: Thirty-eight MTM eyes with axial length less than 26.5 mm were prospectively enrolled. Thirty-one eyes received surgery, and they were followed up for at least 6 months. Characteristics of MTM and surgical outcomes were evaluated. RESULTS: Of the MTM eyes, 92.11% (35/38) showed posterior staphyloma. Narrow macular staphyloma was the most common type (54.29%, 19/35), followed by peripapillary (37.14%, 13/35). Three cases (8.57%) had wide macular staphyloma, and 44.74% of cases (17/38) had vitreoretinal traction. Twenty-two MTM eyes of type T3 underwent macular buckling surgery, and all the cases achieved foveal reattachment after the surgery. The mean best-corrected visual acuity improved significantly at the 6-month follow-up (P < 0.001). Nine MTM eyes of type T4 or T5 received combined surgery, all macular holes recovered, and the best-corrected visual acuity also improved postoperatively (P = 0.008) as of the 6-month visit. CONCLUSION: Posterior staphyloma might serve as the initial force of the pathogenesis of MTM in eyes with axial length ˂26.5 mm. Macular buckling is a productive way to improve the MTM.

Visual Field Sensitivity Prediction Using Optical Coherence Tomography Analysis in Hydroxychloroquine Toxicity.

Purpose: This study investigates the association between local retina structure and visual function in a cohort with long-term hydroxychloroquine (HCQ) use. Methods: The study included 84 participants (54 participants without toxicity and 30 participants with toxicity) with history of chronic HCQ use (14.5 ± 7.4 years) who had testing with spectral-domain optical coherence tomography (SD-OCT) imaging and Humphrey 10-2 visual fields. Optical coherence tomography (OCT) metrics (total and outer retina thickness [TRT and ORT], minimum intensity [MinI], and ellipsoid zone [EZ] loss) were sampled in regions corresponding to visual field test locations. Univariate linear correlations were investigated and a multivariate random forest regression using a combination of OCT metrics was used to predict visual field sensitivity by locus using a leave-one-out cross-validation strategy. Results: In univariate linear regression, EZ loss demonstrated the strongest relationship with visual field sensitivities in the parafoveal ring with R2 = 0.58. TRT and ORT revealed positive correlations with visual field sensitivity (R2 = 0.57 and 0.40, respectively), whereas total and outer retinal MinI yielded negative correlations (R2 = 0.10 and 0.22). The multivariate model improved correlations (R2 = 0.66) yielding a root mean squared error of 3.8 decibel (dB). Feature importance analysis identified EZ loss as the most relevant predictor of function. Conclusions: Multiple OCT-derived quantitative metrics used in combination can provide information to predict local sensitivities. The results indicate a strong relationship between retinal function and OCT measures, which contribute to the understanding of the retinal toxicity caused by HCQ as well as being applicable to outcome development for other degenerative diseases of the outer retina.

Age dependence of retinal vascular plexus attenuation in the triple transgenic mouse model of Alzheimer's disease.

The influence of Alzheimer's disease (AD) progression and severity on the structural and functional integrity of the cerebral vasculature is well recognized. The retina is an extension of the brain; thus, changes in retinal vascular features may serve as markers of AD cerebrovascular pathologies. However, differentiating normal aging-versus AD-induced retinal vascular changes is unresolved. Therefore, we compared and quantified changes in superficial (SVP), intermediate (IVP), and deep (DVP) retinal vascular plexuses in young, middle-age, and old triple transgenic mouse model of AD (3xT-AD) to the changes that occur in age-matched controls (C57BL/6j). We used immunostaining combined with a novel tissue optical clearing approach along with a computational tool for quantitative analysis of vascular network alterations (vessel length and density) in SVP, IVP, and DVP. All three layers had comparable structural features and densities in young 3xTg-AD and control animals. In controls, IVP and DVP densities decreased with aging (-14% to -32% change from young to old, p < 0.05), while no changes were observed in SVP. In contrast, vascular parameters in the transgenic group decreased in all three layers with aging (-12% to -49% change from young to old, p < 0.05). Furthermore, in the old group, SVP and DVP vascular parameters were lower in the transgenics compared to age-matched controls (p < 0.05). Our analysis demonstrates that normal aging and progression of AD lead to various degrees of vascular alterations in the retina. Specifically, compared to normal aging, changes in vascular features of SVP and DVP regions of the retina are accelerated during AD progression. Considering recent advances in the field of depth-resolved imaging of retinal capillary network and microangiography, noninvasive quantitative monitoring of changes in retinal vascular network parameters of SVP and DVP may serve as markers for diagnosis and staging of Alzheimer's disease and discriminating AD-induced vascular attenuation from age-related vasculopathy.

OCULAR SURFACE TEMPERATURE DIFFERENCES IN RETINAL VASCULAR DISEASES.

PURPOSE: To define the effect of age-related macular degeneration (AMD) and diabetic retinopathy (DR) on the ocular thermographic profile. METHODS: This retrospective cross-sectional study included subjects diagnosed with DR or AMD between January and April 2019. Individuals without ocular disease served as controls. A thermal imaging camera was used for ocular surface temperature (OST) acquisition. The mean temperatures of the medial cantus, lateral cantus, and cornea were calculated. RESULTS: Thermographic images were obtained from 133 subjects (260 eyes, 97 DR and 163 AMD) and 48 controls (55 eyes). Ocular surface temperature was higher among patients with AMD and lowest among patients with DR (P < 0.001). A subgroup analysis revealed that eyes with diabetic macular edema had significantly higher OSTs than DR eyes without diabetic macular edema. Moreover, the OST in eyes with diabetic macular edema was similar to the measurements of the AMD group. There were no differences in OSTs between neovascular and nonneovascular AMD eyes. CONCLUSION: Although AMD and DR are considered posterior segment conditions, their effect on OST implies that the entire globe is involved. Although both conditions result from similar multifactorial pathophysiologic changes, the differences in OST between DR and AMD might be due to dissimilarity in the balance of pathologic processes involved in each condition. Further research is required to better understand the pathophysiology of these diseases and their effect on OST as well as to determine the effect of vasculature, circulation, and tissue metabolism on ocular temperature.

BACILLARY LAYER DETACHMENT OVERLYING REDUCED CHORIOCAPILLARIS FLOW IN ACUTE IDIOPATHIC MACULOPATHY.

PURPOSE: To report new multimodal imaging features that enhance our understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months. METHODS: A 31-year-old man presented with acute central vision loss in his right eye due to coxsackievirus-associated AIM. Serial multimodal retinal imaging including confocal true color fundus photography, blue-light fundus autofluorescence (BAF), near-infrared reflectance (NIR), spectral domain optical coherence tomography and swept-source optical coherence tomography (SD-OCT + SS-OCT), and en face SS-OCT angiography (SS-OCTA) were performed over a 3.5-month follow-up. Eidon true color confocal scanner camera (Centervue, Padova, Italy) was used for color and BAF imaging. Near-infrared reflectance and SD-OCT images were obtained with the Heidelberg Spectralis OCT (HRA2 + OCT; Heidelberg Engineering, Heidelberg, Germany). For SS-OCT and en face SS-OCT and SS-OCTA images, the PLEX Elite 9,000 (Carl Zeiss Meditec, Inc, Dublin, CA) was used. Central alterations in choriocapillaris flow were analyzed with SS-OCTA using the University of Washington choriocapillaris (CC) flow deficit quantification algorithm available through the ARI Network. Flow deficit area and density values were analyzed and compared between the first and last examinations. Corresponding en face OCT imaging was used to distinguish true flow defects from artifacts secondary to shadowing. RESULTS: In the acute stage of AIM, a bacillary layer detachment appearing as a yellow-grayish foveal elevation surrounded by a hypopigmented parafoveal ring was evident in a Bull's eye configuration, corresponding to a hyperreflective ring upon NIR and a hyperautofluorescent ring with BAF. SD + SS-OCT showed mostly intraretinal fluid consistent with a bacillary layer detachment in conjunction with a thickened inner choroid. At presentation, SS-OCTA demonstrated a marked reduction of choriocapillaris flow signal. At 1 week, early resolution of retinal fluid was followed by restoration of the ellipsoid zone at 5 weeks, while restoration of the interdigitation zone and reduction in retinal pigment epithelium/Bruch membrane complex thickening occurred more slowly. Swept-source OCT angiography showed a gradual, but incomplete, recovery of inner choroidal flow signal at 3.5-month follow-up. CONCLUSION: Acutely, AIM may present with a photoreceptor splitting foveal bacillary layer detachment associated with a marked reduction in inner choroidal flow signal on SS-OCTA. Thereafter, restoration of the outer retinal layers and gradual normalization of choroidal flow signal appear to support the often-benign nature of the disease.

Examination of Large Artery Atherosclerosis could Reveal Small Artery Retinopathy in Untreated Middle-Aged Individuals.

AIMS: Small arteries can be visualized in the ocular fundus, and findings of retinopathy based on Scheie classification are often applied to evaluate the impact of hypertension and atherosclerosis. However, the relationship between damage in the large and small arteries has not been investigated sufficiently, especially in the early stages. The present study investigated possible associations between large artery atherosclerosis and small artery retinopathy in untreated middle-aged individuals. METHODS: Untreated middle-aged workers undergoing periodic health check-ups (n=7,730, 45±8 years) were enrolled in this study. The absence or presence and extent of retinopathy were characterized by ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4) based on Scheie classification. Large artery atherosclerosis was examined based on functional assessment of the cardio-ankle vascular index (CAVI) and morphological assessment of the carotid intima-media thickness (IMT) by ultrasound. RESULTS: We found significant differences in CAVI and carotid IMT between individuals with and without hypertensive or atherosclerotic retinopathy. Multivariable regression analysis showed that the presence of hypertensive and atherosclerotic retinopathy was significantly associated with CAVI and carotid IMT. Logistic regression analysis with the endpoint of a hypertensive or atherosclerotic lesion revealed that CAVI and carotid IMT are independent determinants of retinopathy. CONCLUSIONS: CAVI and carotid IMT were significantly associated with the presence of retinopathy based on Scheie classification in untreated middle-aged subjects, implying that atherosclerotic examination in large arteries could reveal early-stage small artery retinopathy.

Analysis of Radial Peripapillary Capillary Density in Patients with Bietti Crystalline Dystrophy by Optical Coherence Tomography Angiography / 生物医学与环境科学（英文）

OBJECTIVE@#We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD).@*METHODS@#We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two.@*RESULTS@#The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD.@*CONCLUSION@#The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.

MICROVASCULAR LEAKAGE IS A POOR PROGNOSTIC FACTOR FOR IDIOPATHIC EPIRETINAL MEMBRANE: A Fluorescein Angiography Study.

PURPOSE: To investigate the angiographic findings assessed using fluorescein angiography and their prognostic values of idiopathic epiretinal membrane. METHODS: Seventy-three eyes of idiopathic epiretinal membrane that had been followed up for 6 months after surgical treatment were included. Midphase fluorescein angiography images were obtained at baseline. Structural changes, including central subfield macular thickness, intraretinal cystic lesion, and ectopic inner retinal layer on the fovea, were assessed using optical coherence tomography. The main outcome measures were microvascular leakage (ML) and its association with optical coherence tomography findings and best-corrected visual acuity (BCVA). RESULTS: Of a total of 73 eyes, 37 showed ML and had worse BCVA (P = 0.040), greater central subfield macular thickness (P = 0.028), and more ectopic inner retinal layer (P < 0.001) than those without ML at baseline. Also, ML was associated with worse postoperative BCVA (P < 0.001) and ectopic inner retinal layers (P < 0.001; P = 0.034) at baseline and 6 months. The baseline factors associated with postoperative BCVA of ≥20/25 were better BCVA (P = 0.027) and the absence of ML (P < 0.001). CONCLUSION: Half of the idiopathic epiretinal membrane eyes showed that ML was associated with inner retinal deformity and poor visual recovery. Fluorescein angiography helped to predict visual prognosis after idiopathic epiretinal membrane surgery.

Chronic social defeat stress causes retinal vascular dysfunction.

PURPOSE: The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. METHODS: Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy. RESULTS: No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD. CONCLUSIONS: We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process.

The characteristics of choriocapillaris flow void in the unilateral polypoidal choroidal vasculopathy fellow eyes.

To evaluate the morphological characteristics of flow void (FV) in the fellow eyes of the unilateral polypoidal choroidal vasculopathy (PCV). Fifty PCV fellow eyes (PCVF) and 31 age-matched normal ocular circulation controls were recruited in this retrospective study. The number of FV was analyzed according to the size in a centered 5 × 5 mm swept source optical coherence tomography angiography scans. We used indocyanine green angiography images to determine whether choroidal vascular hyperpermeability (CVH) has occurred. For the PCVF, the prevalence rate of CVH was 70% (35 of 50) The number of FVs was significantly lower in 400-25,000 µm2 (P = 0.005), 400-500 µm2 (P = 0.001), 525-625 µm2 (P = 0.001) and 650-750 µm2 (P = 0.018). compared to the controls. And showed no difference in size from 775 to 1125 µm2 between the two groups. The area under the receiver operating characteristic curve of PCVF with CVH and controls was 0.94 (95% CI 0.88-1.00) (P < 0.001). We found that the number of small FVs was significantly lower in the PCV fellow eyes than that in the eyes with control group.

Impact of Structural Changes on Multifocal Electroretinography in Patients With Use of Hydroxychloroquine.

Purpose: To investigate the relationship between retinal structure and macular function in eyes screened for hydroxychloroquine (HCQ) toxicity. Methods: Participants referred for hydroxychloroquine retinopathy screening with spectral domain optical coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) testing were included in the analysis. Amplitude and implicit time of mfERG N1 and P1 responses were included in the analysis. Ring ratios were computed for amplitude values as the ratio of rings 1-3:5 (R1-3:R5). A control group of healthy participants was included for comparison of SD-OCT metrics. Results: Sixty-three eyes screened for HCQ retinopathy and 30 control eyes were analyzed. The outer nuclear layer (ONL) was significantly thinner in HCQ patients in the foveal (P = 0.008), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions. The HCQ cohort was further divided into two subgroups according to the presence of structural clinically detectable retinopathy (i.e., structural damage as detected by multimodal imaging). HCQ eyes without retinopathy had a thinner ONL thickness in the foveal (P = 0.032), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions and a thinner inner nuclear layer (INL) in the parafoveal region (P = 0.045 versus controls). Structural changes in HCQ patients without retinopathy were significantly associated with macular function as R2:R5 ring ratio of mfERG P1 amplitude was associated with INL (P = 0.002) and ONL (P = 0.044) thicknesses, and R3:R5 ring ratio of P1 amplitude was associated with ONL thickness (P = 0.004). Conclusions: Our results suggest that structural alterations secondary to HCQ toxicity may occur in the absence of clinically detectable retinopathy, and this may reflect in an impaired macular function.

Targeting the Angiopoietin/Tie Pathway: Prospects for Treatment of Retinal and Respiratory Disorders.

Anti-angiogenic approaches have significantly advanced the treatment of vascular-related pathologies. The ephemeral outcome and known side effects of the current vascular endothelial growth factor (VEGF)-based anti-angiogenic treatments have intensified research on other growth factors. The angiopoietin/Tie (Ang/Tie) family has an established role in vascular physiology and regulates angiogenesis, vascular permeability, and inflammatory responses. The Ang/Tie family consists of angiopoietins 1-4, their receptors, tie1 and 2 and the vascular endothelial-protein tyrosine phosphatase (VE-PTP). Modulation of Tie2 activation has provided a promising outcome in preclinical models and has led to clinical trials of Ang/Tie-targeting drug candidates for retinal disorders. Although less is known about the role of Ang/Tie in pulmonary disorders, several studies have revealed great potential of the Ang/Tie family members as drug targets for pulmonary vascular disorders as well. In this review, we summarize the functions of the Ang/Tie pathway in retinal and pulmonary vascular physiology and relevant disorders and highlight promising drug candidates targeting this pathway currently being or expected to be under clinical evaluation for retinal and pulmonary vascular disorders.

A look into retinal organoids: methods, analytical techniques, and applications.

Inherited retinal diseases (IRDs) cause progressive loss of light-sensitive photoreceptors in the eye and can lead to blindness. Gene-based therapies for IRDs have shown remarkable progress in the past decade, but the vast majority of forms remain untreatable. In the era of personalised medicine, induced pluripotent stem cells (iPSCs) emerge as a valuable system for cell replacement and to model IRD because they retain the specific patient genome and can differentiate into any adult cell type. Three-dimensional (3D) iPSCs-derived retina-like tissue called retinal organoid contains all major retina-specific cell types: amacrine, bipolar, horizontal, retinal ganglion cells, Müller glia, as well as rod and cone photoreceptors. Here, we describe the main applications of retinal organoids and provide a comprehensive overview of the state-of-art analysis methods that apply to this model system. Finally, we will discuss the outlook for improvements that would bring the cellular model a step closer to become an established system in research and treatment development of IRDs.

Insights on the Regeneration Potential of Müller Glia in the Mammalian Retina.

Müller glia, the major glial cell types in the retina, maintain retinal homeostasis and provide structural support to retinal photoreceptors. They also possess regenerative potential that might be used for retinal repair in response to injury or disease. In teleost fish (such as zebrafish), the Müller glia response to injury involves reprogramming events that result in a population of proliferative neural progenitors that can regenerate the injured retina. Recent studies have revealed several important mechanisms for the regenerative capacity of Müller glia in fish, which may shed more light on the mechanisms of Müller glia reprogramming and regeneration in mammals. Mammalian Müller glia can adopt stem cell characteristics, and in response to special conditions, be persuaded to proliferate and regenerate, although their native regeneration potential is limited. In this review, we consider the work to date revealing the regenerative potential of the mammalian Müller glia and discuss whether they are a potential source for cell regeneration therapy in humans.

OUTCOMES IN PATIENTS RESUMING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOLLOWING TREATMENT DELAY DURING THE CORONAVIRUS-19 PANDEMIC.

PURPOSE: To evaluate the outcomes of delay in care secondary to the coronavirus pandemic in patients requiring intravitreal anti-vascular endothelial growth factor therapy. METHODS: A retrospective review was performed, and subjects were divided into two groups: 1) a study group of patients who experienced a treatment delay of ≥6 weeks from the intended follow-up during the coronavirus pandemic and resumed treatment with ≥2 anti-vascular endothelial growth factor injections over 6 months following treatment delay, and 2) a control group of patients who received regular care throughout the coronavirus pandemic. RESULTS: Totally, 234 subjects were analyzed. The mean treatment delay from the intended follow-up in the study group was 11.8 (±4.0) weeks. Visual acuity and central macular thickness worsened from baseline to 6 months after resuming anti-vascular endothelial growth factor therapy in the study group (P < 0.0001 and P = 0.001, respectively). Visual acuity and central macular thickness were better in the control group compared with the study group at the end of the 6-month study period (P < 0.0001 for both). CONCLUSION: Treatment delay in subjects undergoing anti-vascular endothelial growth factor therapy for retina disease during the coronavirus pandemic had worse visual and anatomical outcomes despite reinitiating treatment over 6 months compared with a control group, suggesting irreversibility and permanence of outcomes.

Asymptomatic retinal dysfunction in alpha-methylacyl-CoA racemase deficiency.

Purpose: Alpha-methylacyl-CoA racemase (AMACR) deficiency is a peroxisomal disorder due to biallelic mutations in AMACR. At least 13 genetically confirmed patients have been reported to date. Seven had obvious pigmentary retinopathy; however, for the other six, no retinal phenotype was mentioned. The purpose of this report is to document subtle retinal findings in an additional affected family. Methods: Retrospective case series (three affected siblings and their unaffected parents). Results: Three Arab siblings (16, 19, and 22 years old) with prior juvenile cholelithiasis had been diagnosed with AMACR deficiency based on biochemical analysis, whole exome sequencing, and confirmatory segregation analysis (AMACR NM_001167595.1: c.877T>C; p.C293R). For all three, there were no visual complaints, but retinal multimodal imaging and electroretinography suggested subtle retinal dysfunction. Conclusions: Retinal dysfunction is a parameter that should be measured in patients with known or suspected AMACR deficiency even in the absence of visual symptoms. This may be helpful with clinical diagnosis and monitoring response to dietary interventions.