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Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.

Purpose. To determine the effects of cataract surgery on contrast visual acuity and retinal sensitivity in patients with retinitis pigmentosa. Methods. Retinal sensitivity and contrast visual acuity were determined by microperimetry (MAIA) and contrast sensitivity acuity tester (CAT-CP), respectively, before and after cataract surgery. The significance of the correlations between visual acuity, retinal sensitivity, contrast visual acuity, improvements after surgery, and macular structure before and after cataract surgery was determined. Results. Retinal sensitivity and contrast visual acuity were significantly improved after cataract surgery. The correlations among postoperative visual acuity, postoperative retinal sensitivities, and preoperative ellipsoid zone length were significant. The postoperative retinal sensitivity of the central 10° and the ellipsoid zone length was particularly significantly correlated. Preoperative contrast visual acuity and the amount of improvement and preoperative retinal sensitivity and the amount of improvement were significantly negatively correlated. The contrast visual acuity under both the 100% and 10% photopic and mesopic conditions improved significantly after cataract surgery. Conclusions. Cataract surgery in retinitis pigmentosa patients with preserved ellipsoid zones significantly improved retinal sensitivity and contrast visual acuity. Cataract surgery can be expected to improve retinal sensitivity and contrast visual acuity under various conditions, even if preoperative visual parameters are low, as long as the ellipsoid zone is preserved.

Diabetic retinopathy (DR) is a diabetic complication affecting the eyes, which is the main cause of blindness in young and middle-aged people. In order to speed up the diagnosis of DR, a mass of deep learning methods have been used for the detection of this disease, but they failed to attain excellent results due to unbalanced training data, i.e., the lack of DR fundus images. To address the problem of data imbalance, this paper proposes a method dubbed retinal fundus images generative adversarial networks (RF-GANs), which is based on generative adversarial network, to synthesize retinal fundus images. RF-GANs is composed of two generation models, RF-GAN1 and RF-GAN2. Firstly, RF-GAN1 is employed to translate retinal fundus images from source domain (the domain of semantic segmentation datasets) to target domain (the domain of EyePACS dataset connected to Kaggle (EyePACS)). Then, we train the semantic segmentation models with the translated images, and employ the trained models to extract the structural and lesion masks (hereafter, we refer to it as Masks) of EyePACS. Finally, we employ RF-GAN2 to synthesize retinal fundus images using the Masks and DR grading labels. This paper verifies the effectiveness of the method: RF-GAN1 can narrow down the domain gap between different datasets to improve the performance of the segmentation models. RF-GAN2 can synthesize realistic retinal fundus images. Adopting the synthesized images for data augmentation, the accuracy and quadratic weighted kappa of the state-of-the-art DR grading model on the testing set of EyePACS increase by 1.53% and 1.70%, respectively.

Background. Diabetic retinopathy (DR) is a leading cause of blindness in working-age populations. Proper in vitro DR models are crucial for exploring pathophysiology and identifying novel therapeutic targets. This study establishes a rational in vitro diabetic retinal neuronal-endothelial dysfunction model and a comprehensive downstream validation system. Methods. Human retinal vascular endothelial cells (HRMECs) and retinal ganglion cells (RGCs) were treated with different glucose concentrations with mannitol as matched osmotic controls. Cell proliferation and viability were evaluated by the Cell Counting Kit-8. Cell migration was measured using a transwell migration assay. Cell sprouting was assessed by a tube formation assay. The VEGF expression was assessed by ELISA. RGCs were labeled by neurons and RGC markers TUJ1 and BRN3A for quantitative and morphological analysis. Apoptosis was detected using PI/Hoechst staining and TUNEL assay and quantified by ImageJ. Results. Cell proliferation and migration in HRMECs were significantly higher in the 25 mM glucose-treated group ( p < 0.001 ) but lower in the 50 mM and 100 mM groups ( p < 0.001 ). The permeability and the apoptotic index in HRMECs were statistically higher in the 25 mM, 50 mM, and 100 mM groups ( p < 0.05 ). The tube formation assay found that all the parameters were significantly higher in the 25 mM and 50 mM groups ( p < 0.001 ) concomitant with the elevated VEGFA expression in HRMECs ( p = 0.016 ). Cell viability was significantly lower in the 50 mM, 100 mM, and 150 mM groups in RGCs ( p 50 mM = 0.013 , p 100 mM = 0.019 , and p 150 mM = 0.002 ). Apoptosis was significantly elevated, but the proportion of RGCs with neurite extension was significantly lower in the 50 mM, 100 mM, and 150 mM groups ( p 50 mM < 0.001 , p 100 m M < 0.001 , and p 150 mM < 0.001 ). Conclusions. We have optimized glucose concentrations to model diabetic retinal endothelial (25-50 mM) or neuronal (50-100 mM) dysfunction in vitro, which have a wide range of downstream applications.

Retinal degenerative diseases are one of the main causes of complete blindness in aged population. In this study, we compared the therapeutic potential for retinal degeneration of human mesenchymal stem cells derived from abdominal subcutaneous fat (ABASCs) or from orbital fat (OASCs) due to their accessibility and mutual embryonic origin with retinal tissue, respectively. OASCs were found to protect RPE cells from cell death and were demonstrated to increase early RPE precursor markers, while ABASCs showed a raise in retinal precursor marker expression. Subretinal transplantation of OASCs in a mouse model of retinal degeneration led to restoration of the RPE layer while transplantation of ABASCs resulted in a significant restoration of the photoreceptor layer. Taken together, we demonstrated a lineage-specific therapeutic effect for either OASCs or ABASCs in retinal regeneration.

Purpose. To investigate structural and functional correlations in glaucoma patients using optic nerve head hemoglobin (ONH Hb) measurements as determined by automated colorimetric analysis of conventional retinography. Methods. We prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (standard automated perimetry, SAP), color fundus imaging (mydriatic retinography), and peripapillary retinal nerve fiber layer (pRNFL) assessment through spectral-domain optical coherence tomography (SD-OCT). Software Laguna ONhE was used to estimate the amount of ONH Hb and to determine the glaucoma discriminant function (GDF) index. Scatter plots were constructed, and regression analysis was used to investigate the correlations between GDF, average pRNFL thickness, and VF mean deviation (VFMD) index values. A secondary analysis was performed to compare each parameter between three different glaucoma groups divided according to VFMD values (mild, >−6 dB; moderate, −6 to −12 dB; and advanced, p ≤ 0.001 ). The comparison of each parameter according to groups of disease stages revealed significant differences between controls and each of the glaucomatous groups ( p < 0.001 ). More pronounced changes in GDF values were observed in early disease stages. We found significant nonlinear correlations between GDF and VFMD values (R2 = 0.295, p < 0.001 ) and between pRNFL thickness and VFMD (R2 = 0.598, p < 0.001 ). A linear correlation was found between GDF and pRNFL thickness values (R2 = 0.195, p < 0.001 ). Conclusion. Our results showed significant associations between ONH Hb values and both structural and functional damage in glaucoma obtained by SD-OCT and SAP, respectively. The nonlinear correlation we found and the GDF behavior along different disease stages suggest that ONH Hb levels’ reduction may precede visual function changes in early glaucoma stages.

Purpose. This study aimed to investigate the characteristics of retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and choroidal thickness in children with moderate-to-high hyperopia (MHH). Methods. This was a cross-sectional study that enrolled 53 children with MHH and 53 emmetropic children. Subjects with a spherical equivalent refraction (SER) of +4.0 D or higher were included in the MHH group, and subjects with SER between −1.0 D and +1.0 D were included in the emmetropic group. Ophthalmic examinations, including uncorrected visual acuity, cycloplegic refraction, slit-lamp examination, axial length, and swept-source optical coherence tomography (SS-OCT; DRI OCT Triton-1, Topcon, Tokyo, Japan), were performed. Results. The RNFL and GCL in the temporal and inferior quadrants in 1–3 mm of the macular fovea were thinner in the MHH group than in the emmetropic group (all P < 0.05 ). The MHH group also had a thicker choroidal thickness in all regions (all P < 0.05 ). The SER was independently correlated with the average choroidal thickness in the optic disc and fovea (coefficient = 4.853, P < 0.001 for the optic disc; coefficient = 5.523, P = 0.004 for the fovea), while axial length was negatively correlated with choroidal thickness (coefficient = −12.649, P < 0.001 ). Axial length was positively associated with RNFL and GCL thickness in the temporal quadrant in 1–3 mm of the macular fovea (coefficient = 0.966, P = 0.007 for RNFL and coefficient = 1.476, P = 0.011 for the macular fovea). Conclusion. Compared with emmetropic children, MMH children had greater choroidal thickness. The characteristics of the RNFL and GCL thickness in MMH children were different from those in emmetropic children.

An unusual case of nitroglycerin-induced Paracentral Acute Middle Maculopathy (PAMM) is presented. A 50-year-old patient with sudden vision loss and scotoma was followed up with swept-source optical coherence tomography (SS-OCT), optical coherence tomography-angiography (OCT-A), and fluorescein angiography (FA). An anal fissure treated with glyceryl trinitrate (GTN) 0.2% ointment with headache and dizziness after application was reported. Fundoscopy OS revealed mild retinal venous dilatation and tortuosity with scattered blot hemorrhages and subtle, parafoveal, whitish lesions in the outer retina. SS-OCT revealed diffuse, hyperreflective lesions in the inner plexiform (IPL), inner nuclear (INL), and outer plexiform layers (OPL). OCT-A revealed focal dropout in the deep capillary plexus. FA showed masking due to blot hemorrhages and early punctuate leakage in the inner retina. This entity was identified as nitroglycerin-induced PAMM. Over the following 8 months, after discontinuation of the ointment application, the patient was symptom-free with stable visual acuity. OCT revealed INL/OPL thinning and confirmed complete lesion resolution. This first report of retinal vascular abnormalities due to nitrite ointment provides an insight into an unknown side effect of nitroglycerin ointment use. A dose-dependent correlation between GTN application and retinal vascular abnormalities remains to be confirmed.

Purpose. To report the occurrence of acute, bilateral, central serous chorioretinopathy (CSC), and pachychoroid spectrum disorder findings in patients with coronavirus disease 2019 (COVID-19). Methods. In recovered cases of COVID-19 with visual disturbances, complete ocular examinations with multimodal retinal and choroidal evaluation, including enhanced depth imaging optical coherence tomography, fluorescein or indocyanine green angiography, and blue autofluorescence, were obtained. Results. Four COVID-19 recovered patients presented with bilateral blurred vision. Ocular examination and imaging revealed pachychoroid and pachyvessels associated with choroidal hyperpermeability without any obvious intraocular inflammation. Bilateral localized serous retinal detachment was obvious in three cases compatible with pachychoroid associated with CSC manifestation and pachychoroid pigment epitheliopathy in one patient. CSC was resolved with treatment by steroidal antimineralocorticoid (Eplerenone) in two patients and by photodynamic therapy in one patient. None of the patients reported emotional stress and history of corticosteroid consumption. Conclusion. Hyperpermeability of the choroid, pachychoroidopathy, or choroidal vessel congestion can be observed or exacerbated in association with COVID-19.

Background. To report a patient with central retinal artery occlusion (CRAO) associated with sildenafil overdose. Case Presentation. A forty-two-year-old male presented three hours after sudden painless visual loss in the right eye. BCVA was counting finger in two meters, and relative afferent pupillary defect was positive. Fundus examination revealed retinal whiteness except in a limited area of papillomacular bundle and cherry red spot. He consumed two 100 mg film-coated sildenafil tablet (Vizarsin, Krka, d.d., Novo mesto, Slovenia) twelve hours apart, and the last one was six hours before visual loss. He was diagnosed with CRAO with cilioretinal artery sparing. Although we did not find any emboli, anterior chamber paracentesis was done. Four weeks later, BCVA improved to 20/80, with resolving of retinal edema. Cardiovascular, carotid arteries, and neurologic evaluations were negative for any predisposing factor. Conclusion. CRAO is a vision threatening condition that might be associated with the overdose of sildenafil.

Purpose. To review the current literature on retinal displacement and provide a discussion of potential risk factors, postoperative outcomes, and future directions. Methods. Two databases, MEDLINE and EMBASE, were mined using a directed search strategy to identify all articles on retinal displacement. Results. We identified 1522 articles. A total of n = 14 articles were retained. We provide an overview on the potential influence of surgical type (n = 4), tamponade agents (n = 5), postoperative posture (n = 6), and preoperative retinal status (n = 5) on incidence of retinal displacement and visual outcomes (n = 8). Discussion. Pars plana vitrectomy (PPV) with gas tamponade is associated with displacement rates of up to 72%, typically in a downward direction. Meanwhile, pneumatic retinopexy and PPV with silicone oil may offer similar surgical success with a significantly lower risk of displacement. The impact of heavy liquids such as perfluorocarbon liquid, postoperative positioning and preoperative extent of detachment on displacement remains inconclusive. Patients with displacement had a significantly lower visual acuity and higher rates of distortion than those without displacement. However, not all patients with displacement experienced visual symptoms. Conclusion. Retinal displacement is a new concept in our understanding of retinal detachment. Additional studies are needed to better define its impact on postsurgical outcomes.

Irreversible loss of retinal ganglion cells (RGCs) is a common pathological feature of various optic nerve degenerative diseases such as glaucoma and ischemic optic neuropathy. Effective protection of RGCs is the key to successful treatment of these diseases. Total Panax notoginseng saponins (TPNS) are the main active component of Panax notoginseng, which has an inhibitory effect on the apoptosis pathway. This study is aimed at assessing the protective effect of TPNS on RGCs of the optic nerve crush (ONC) model of rats and exploring the underlying mechanisms. The intraperitoneal or intravitreal injection of TPNS was used based on the establishment of the rat ONC model. Fifteen days after the injury, the cell membrane fluorescent probe (Fluoro-Gold) was applied to retrograde RGCs through the superior colliculus and obtain the number of surviving RGCs. TUNEL assay was also used to detect the number and density of RGC apoptosis after the ONC model. The expression and distribution of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK in the retina were demonstrated by Western blot analysis. After the intervention of TPNS, the rate of cell survival increased in different retinal regions ( p < 0.05 ) and the number of apoptosis cells decreased. Regarding the expression of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK-related apoptotic proteins, TPNS can reduce the level of apoptosis and play a role in protecting RGCs ( p < 0.05 ). These findings indicate that topical administration of TPNS can inhibit cell apoptosis and promote RGC survival in the crushed optic nerve.

Diabetic retinopathy is characteristic of a local distribution that involves early-stage risk factors and can forecast the evolution of the illness or morphological lesions related to the abnormality of retinal blood flows. Regional variations in retinal blood flow and modulation of retinal capillary width in the macular area and the retinal environment are also linked to the course of diabetic retinopathy. Despite the fact that diabetic retinopathy is frequent nowadays, it is hard to avoid. An ophthalmologist generally determines the seriousness of the retinopathy of the eye by directly examining color photos and evaluating them by visually inspecting the fundus. It is an expensive process because of the vast number of diabetic patients around the globe. We used the IDRiD data set that contains both typical diabetic retinopathic lesions and normal retinal structures. We provided a CNN architecture for the detection of the target region of 80 patients’ fundus imagery. Results demonstrate that the approach described here can nearly detect 83.84% of target locations. This result can potentially be utilized to monitor and regulate patients.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly people. Neovascular AMD (nAMD) is responsible for the majority of cases of severe visual loss in eyes with AMD. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow-up of nAMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response. The aim of this review is to describe and analyze various structural OCT-based biomarkers, which have practical value during both initial assessment and treatment follow-up of nAMD patients. While central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management. The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid) will be discussed firstly. In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analyzed in detail. The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub-RPE hyperreflective columns, prechoroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with nAMD progression. OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. This up-to-date review article provides a comprehensive description on how structural OCT-based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in nAMD patients. Thus, in this perspective, clinicians will be able to allocate hospital resources in the best possible way and tailor treatment to the individual patient’s needs.

Purpose. Using retinal optical coherence tomography angiography (OCTA), we aimed to investigate the changes in important indicators of cerebral microcirculatory disorders, such as the properties of the radial peripapillary capillaries, vascular complexes, and the retinal nerve fiber layer, caused by carotid stenosis and postoperative reperfusion. Methods. In this prospective longitudinal cohort study, we recruited 40 carotid stenosis patients and 89 healthy volunteers in the First Affiliated Hospital of Harbin Medical University (Harbin, China). Eyes with ipsilateral carotid stenosis constituted the experimental group, while the fellow eyes constituted the contralateral eye group. Digital subtraction angiography, CT perfusion imaging (CTP), and OCTA examinations were performed in all subjects. The vessel density of the radial peripapillary capillaries (RPC), superficial retinal vascular complexes (SVC), deep vascular complexes (DVC), choriocapillaris (CC), and the thickness of the retinal nerve fiber layer (RNFL) were assessed. Propensity-matched analysis was undertaken to adjust for covariate imbalances. Intergroup comparative analysis was conducted, and the paired sample t -test was used to evaluate the preoperative and postoperative changes in OCTA variables. Results. The ocular vessel density in the experimental group was significantly lower than that in the control group (RPC: 55.95 vs. 57.24, P = 0.0161 ; SVC: 48.65 vs. 52.22, P = 0.0006 ; DVC: 49.65 vs. 57.50, P < 0.0001 ). Participants with severe carotid stenosis have reduced contralateral ocular vessel density (RPC 54.30; SVC 48.50; DVC 50.80). Unilateral stenosis removal resulted in an increase in vessel density on both sides, which was detected by OCTA on the 4th day (RPC, P < 0.0001 ; SVC, P = 0.0104 ; DVC, P = 0.0104 ). Moreover, the ocular perfusion was consistent with that established by CTP. Conclusion. OCTA can be used for sensitive detection and accurate evaluation of decreased ocular perfusion caused by carotid stenosis and may thus have the potential for application in noninvasive detection of cerebral microcirculation disorders. This trial is registered with NCT04326842.

Purpose. To evaluate the peripapillary vessel density (pVD) and the peripapillary nerve fiber layer (pRNFL) thickness in patients with chiasmal compression caused by sellar region mass using optical coherence tomography angiography (OCTA). Methods. This is an observational, cross-sectional study of 31 patients (31 eyes) with chiasmal compression caused by sellar region mass and 34 healthy controls (34 eyes). Automated perimetry and OCTA were performed. The pVD and pRNFL thickness were compared between the two groups. The impact of tumor diameter, duration of symptoms, and cavernous sinus (CS) invasion on visual dysfunction, pVD, and pRNFL thickness was also analyzed. Furthermore, we divided the patients into two subgroups according to whether there was an absolute defect in the central visual field and evaluated their pVD and pRNFL thickness, respectively. Results. Compared to the healthy control group, there was a statistically significant decrease in pVD and pRNFL thickness in patients with chiasmal compression ( p < 0.05 ), especially in patients with substantial absolute defects in the central visual field. Tumor diameter, duration of symptoms, and CS invasion did not appear to be associated with pVD and pRNFL thickness. There was a significant positive correlation between the pVD and pRNFL thickness in patients with chiasmal compression ( p < 0.001 ). Conclusion. pVD and pRNFL thickness are significantly decreased in patients with chiasmal compression revealed by OCTA, especially in patients with more severe visual field defects. A significant correlation between pVD and pRNFL thickness was demonstrated, which provides a clue for the study of the mechanism of changes in retinal perfusion in compressive optic neuropathy. It requires considerable attention that OCTA may play an important role in disease monitoring of sellar region mass. Hence, further studies are needed to verify whether OCTA is helpful to predict the prognosis of visual function after decompression surgery.

A 63-year-old Caucasian man with metastatic lung adenocarcinoma undergoing chemotherapy and external radiotherapy was referred for routine eye examination. Although he was asymptomatic, ocular examination revealed a relatively well-circumscribed whitish retinal lesion measuring0.5×0.5×0.5 mm located along the inferotemporal vascular arcade in the right eye. Optical coherence tomography (OCT) showed a hyperreflective dome-shaped lesion occupying the inner retinal layers with few hyperreflective dots overlying the retina in the posterior vitreous consistent with tumor cells. Fluorescein angiography revealed early hyperfluorescence and late staining without leakage at the lesion site. A diagnosis of presumed retinal metastasis from lung adenocarcinoma was made. At 2 months follow-up after completion of chemotherapy, the retinal lesion was found to have regressed completely leaving minor irregularities in the inner retinal layers on OCT. To date, there have been only 41 cases of carcinoma metastasis to the retina reported in the literature including the current case. Despite its rarity, retinal metastasis should be considered in the differential diagnosis of a white-yellow retinal mass with/without overlying vitreous cells especially in patients with a history of systemic cancer.

In this report, we describe a case of timely gas vitrectomy to displace a moderate submacular hemorrhage from the submacular space without tPA, release vitreoretinal traction along the borders of a posterior retinal tear, and analyze postoperative multimodal imaging findings in a 34-year-old male patient whose right eye was injured by a stone. The patient underwent a successful nontissue plasminogen activator gas vitrectomy 3 days after the accident. A multimodal evaluation with spectral-domain optical coherence tomography (SD-OCT), 10-2 and 30-2 campimetry, microperimetry, multifocal electroretinography (mfERG), and visual evoked potentials was performed 6 months after the accident. The multimodal imaging tests yielded abnormal foveal SD-OCT patterns, with a fibrous sealed tear in the retinal pigment epithelium. Campimetry showed low levels of retinal sensitivity; microperimetry and mfERG revealed a subnormal retinal response and a reduction in the N1 and P1 wave amplitudes. The visual evoked potential responses were normal. Multidisciplinary examination at 6 months postoperatively revealed a structurally and functionally abnormal macula. The retina remained attached. Our functional findings indicate that submacular hemorrhage should be treated in a timely manner to minimize photoreceptor damage.

Purpose. To examine the clinical characteristics, outcomes, and rate of unintentional displacement in eyes treated for rhegmatogenous retinal detachment (RRD) with pars plana vitrectomy (PPV) and silicone oil (SO). Methods. This retrospective observational study examined 50 eyes of 50 patients who underwent surgical repair for primary RRD complicated by proliferative vitreoretinopathy (PVR) by PPV and 1000-centistoke SO injection at a single institutional centre. The patients assumed a face-down posture immediately after surgery. Blue-fundus autofluorescence (B-FAF) pictures were obtained at 1 month after surgical procedures using a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). Results. The primary success rate was obtained in 44 eyes (88%), on which the final analysis was conducted. Preoperative PVR was grade A in 7 eyes (15.9%), grade B in 28 eyes (63.6%), and grade C in 9 eyes (20.5%). The fovea was off and the detachment involved both the superior and inferior hemispheres of the retina in all cases. Breaks were located in the upper quadrants in 19 eyes (43.2%), in the lower quadrants in 12 eyes (27.3%), and in both upper and lower quadrants in 13 eyes (29.5%). The mean number of breaks was 3.4 ± 1.9. Intraoperative PFCL was used in 30 eyes (68.2%). Peeling of the epiretinal membrane/internal limiting membrane in the macula area was performed in 13 eyes (29.5%) during the first operation and carried out in all other eyes in occasion of SO removal. Preoperative BCVA was 2.1 ± 1.0 logMAR and improved to 0.8 ± 0.7 logMAR at the last follow-up ( P < 0.0001 ). An upward unintentional retinal displacement was observed in 2 cases (4.5%). Conclusion. PPV and SO tamponade for complicated RRD are associated with good anatomical and functional outcomes and a very low rate of unintentional retinal displacement. Of the factors potentially implicated in favouring displacement that were studied, none were found significant.

Diabetic retinopathy (DR) is a kind of severe retinal neurodegeneration. The advanced glycation end products (AGEs) affect autophagy, and mitochondrial function is involved in DR. Adenosine-activated protein kinase (AMPK) is an important metabolic sensor that can regulate energy homeostasis in cells. However, the effect of AMPK in DR is still not fully understood. In this study, we investigated the effect of AMPK on diabetes-induced photoreceptor cell degeneration. In vivo, a diabetic mouse model was established by streptozotocin (STZ) injection. Haematoxylin-eosin (HE) staining was used to observe retinal morphology and measure the thicknesses of different layers in the retina. Electroretinogram (ERG) was used to evaluate retinal function. In vitro, 661w cells were treated with AGEs with/without an AMPK agonist (metformin) or AMPK inhibitor (compound C). Flow cytometry and CCK-8 assays were used to analyse apoptosis. Mitochondrial membrane potential was analysed by JC-1. Western blotting and qRT-PCR were used to examine the expression of related proteins and genes, respectively. The wave amplitude and the thickness of the outer nuclear layer were decreased in diabetic mice. The expression of rhodopsin and opsin was also decreased in diabetic mice. In vitro, the percentage of apoptotic cells was increased, the expression of the apoptosis-related protein Bax was increased, and Bcl-2 was decreased after AGE treatment in 661w cells. The expression of the autophagy-related protein LC3 was decreased, and p62 was increased. The mitochondrial-related gene expression and membrane potential were decreased, and mitochondrial morphology was abnormal, as observed by TEM. However, AMPK stimulation ameliorated this effect. These results indicate that AMPK stimulation can delay diabetes-induced photoreceptor degeneration by regulating autophagy and mitochondrial function.

Medical records of 75 eyes from 75 consecutive patients with uncomplicated rhegmatogenous retinal detachment (RRD) who underwent pars plana vitrectomy (PPV) were analyzed. Inclusion criteria were patients with RRD who underwent primary 23- or 25-gauge PPV with air, gas, or SiO tamponade and performed by a single surgeon, no use of perfluorocarbon liquids (PFCL) and drainage retinotomy, and follow-up ≥ six months. Exclusion criteria were patients who underwent previous vitreoretinal surgery, proliferative vitreoretinopathy (PVR) more than grade B, giant tears, and encircling band associated with PPV. The main endpoint was the anatomical retinal reattachment rate after a single surgical procedure. Secondary endpoints were best-corrected visual acuity (BCVA), postoperative retinal displacement, and intraoperative and/or postoperative complications. Primary anatomical success was achieved in 97.3% of cases using this modified surgical procedure. Retinal slippage occurred only in 28.2% of patients and it was not observed in all cases of macula-on RRD. The mean logMAR of the BCVA significantly improved in 92% of patients and no intraoperative complications were observed. The results suggest that complete subretinal liquid drainage is not mandatory for all RRD cases treated with PPV and that using PFCL and performing a drainage retinotomy are not essential in eyes with primary RRD and PVR less than grade B. Postoperative positioning after PPV for uncomplicated RRD based on the presence or absence of residual subretinal fluid at the end of surgery could limit the occurrence of postoperative retinal displacement, while promoting patient compliance.

Acute central retinal artery occlusion (CRAO) induces a time-dependent increase in retinal thickness. By manually measuring the relative retinal thickness increase (RRTI) in comparison to the contralateral eye based on optical coherence tomography (OCT), ischemia onset within the past 4.5 hours could be determined with 100% sensitivity and 94.3% specificity. To enable examiner-independent and quicker diagnostics, we analyzed the RRTI using the automatic retinal thickness measurement. In this retrospective study, 28 eyes were evaluated with an acute CRAO (

The emerging literature on the novel coronavirus pandemic has reported several cases of varied retinal findings in patients with COVID-19. We report the case of a 59-year-old male who presented with complaint of bilateral blurry vision following hospital discharge after prolonged hospitalization for severe COVID-19 illness. On ocular exam, the patient demonstrated bilateral cotton wool spots localized to the posterior pole of each eye. Multimodal imaging demonstrated findings consistent with retinal nerve fiber layer infarcts in the areas of the cotton wool spots. Exam and imaging of our patient were most consistent with a Purtscher-like retinopathy. We suggest that as ophthalmologists care for increasing numbers of patients recuperating from COVID-19, they monitor for microangiopathic changes similar to those in our patient.

Purpose. In the present study, the retinal and choroidal vascular densities (VDs) in type 2 diabetes mellitus (DM) patients were analyzed using optical coherence tomography angiography (OCTA). Methods. The study included 282 eyes of 152 patients with type 2 DM (114 without retinopathy, 79 nonproliferative diabetic retinopathy (NPDR), 48 severe NPDR, and 41 proliferative diabetic retinopathy (PDR) eyes). The superficial and deep retinal vessel, choriocapillaris, and choroidal VDs were measured using a binarization method on OCTA images. VDs were compared based on retinopathy severity. Correlations among densities were analyzed. Results. Retinal and choriocapillaris VDs were lower in PDR than in NPDR (all P < 0.05 ). Correlation analysis showed significant positive correlations among densities of superficial and deep retinal vessels and choriocapillaris (all P < 0.001 ). Choroidal VD showed a negative correlation with superficial and deep retinal vessels and choriocapillaris (all P < 0.001 ). Retinal and choriocapillaris VDs showed a negative correlation with diabetic retinopathy (DR) grade (all P < 0.001 ); however, the choroidal VD showed a weak positive correlation ( P = 0.030 ). Conclusion. Choroidal VD increased as retinal and choriocapillaris VDs decreased, indicating that the outer layer of the choroid is less affected by DR severity and VD of larger choroidal vessels may even be increased as a compensatory mechanism for decreased retinal and choriocapillaris VDs in type 2 DM patients.

Purpose. To investigate the hyperreflective foci (HRF) as an inflammatory biomarker using optical coherence tomography angiography (OCTA) in neovascular age-related macular degeneration (AMD) patients after antivascular endothelial growth factor (anti-VEGF) treatment and its association with the retinal microcapillary density. Methods. Twenty-five eyes from 25 patients with neovascular AMD were included in the study. All eyes were imaged with OCTA at baseline (M0) and after 3 consecutive injections (M3; injection performed each month) of anti-VEGF. The number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and outer retina was counted. The vascular density of the fovea, parafovea, and the whole macula, as well as the area of the foveal avascular zone (FAZ), was measured. Results. The mean interval between baseline and follow-up with OCTA was 93.08 ± 5.00 (range, 85-101) days. Compared with the baseline, the number of HRF significantly decreased in DCP ( 7.52 ± 3.06 vs. 3.76 ± 1.48 , P < 0.01 ) and outer retina ( 12.04 ± 4.91 vs. 5.88 ± 3.32 , P < 0.01 ) after treatment. There was no significant difference for HRF number in the SCP, the vascular density (containing foveal, parafoveal, and whole macular), and FAZ area before and after treatments. Conclusion. The number of HRF in DCP and outer retina might serve as an inflammatory biomarker in patients with neovascular AMD. The reduced HRF possibly represents the alleviation of inflammation after anti-VEGF treatment in patients with AMD.

Retinopathy is one of the most severe diabetes-related complications, and macular edema is the major cause of central vision loss in patients with diabetes mellitus. Significant progress has been made in recent years in optical coherence tomography and angiography technology. At the same time, various parameters have been attributed the role of biomarkers creating the frame for new monitoring and treatment strategies and offering new insights into the pathogenesis of diabetic retinopathy and diabetic macular edema. In this review, we gathered the results of studies that investigated various specific OCT (angiography) parameters in diabetic macular edema, such as central subfoveal thickness (CST), cube average thickness (CAT), cube volume (CV), choroidal thickness (CT), retinal nerve fiber layer (RNFL), retinal thickness at the fovea (RTF), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascularity index (CVI), total macular volume (TMV), central choroid thickness (CCT), photoreceptor outer segment (PROS), perfused capillary density (PCD), foveal avascular zone (FAZ), subfoveal neuroretinal detachment (SND), hyperreflective foci (HF), disorganization of the inner retinal layers (DRIL), ellipsoid zone (EZ), inner segment/outer segment (IS/OS) junctions, vascular density (VD), deep capillary plexus (DCP), and superficial capillary plexus (SCP), in order to provide a synthesis of biomarkers that are currently used for the early diagnosis, assessment, monitoring, and outlining of prognosis.

Background. To analyze the optical coherence tomography (OCT) characteristics as well as the clinical and demographic features to investigate their possible role to the course of vitreomacular traction syndrome. Methods. The inclusion criteria were vitreomacular adhesion with traction causing distortion of the retinal architecture, with or without the presence of an epiretinal membrane, regardless of the size of the adhesion; age >18 years; follow-up of at least three months; and adequate quality OCT scan. Measurements of foveal thickness, average macular thickness, macular volume, maximum vertical and horizontal vitreomacular adhesion, nasal and temporal angles of traction, hyaloid hyperreflectivity, the presence of an epiretinal membrane (ERM), and cone outer segment tips detachment were obtained. Results. 150 eyes were included in the analysis. 36 eyes (24%) developed complete resolution at the last visit, 19 eyes (12.7%) formed a full-thickness macular hole, and 95 eyes (63.3%) showed no resolution of the traction. Better BCVA at the first visit was associated with an increased likelihood of resolution of the VMT, but increasing age, CMT, and BCVA in the end of the follow-up was associated with a reduction in the likelihood of resolving. Of the other variables that were studied, no statistical significant predictors were identified. Conclusions. Better BCVA in the first visit was associated with an increased likelihood of resolution of the VMT that occurred in 24% of our cases. Other factors such as the vertical area of adhesion and the angle of adhesion were not identified as prognostic factors affecting the clinical course of the disease.

Purpose. To observe the changes of the retinal nerve fiber layer (RNFL) thickness and the optic disc vessel density (VD) in preclinical diabetic retinopathy (DR) and the relationship between RNFL changes and VD, as well as to investigate the influencing factors on peripapillary vessel density. Methods. This was a cross-sectional study. Thirty-four eyes of 34 type 2 diabetes mellitus (T2DM) patients diagnosed with preclinical diabetic retinopathy (DR) were included in our study, with twenty-three eyes of 23 healthy subjects set up as normal controls. History of diabetes, hypertension, and dyslipidemia was recorded in detail. All participants underwent color fundus photography (CFP), RNFL around the optic disc, and OCT angiography (OCTA) over the optic disc. The 4.5 mm × 4.5 mm Angio Disc scan mode was performed with all participants by using the OCTA instrument. The relationship between changes of RNFL in the four quadrants (superior, inferior, temporal, and nasal) and VD changes was analyzed. Results. Vessel density was significantly lower in the superior (t = −2.27) and temporal (t = −2.02) peripapillary sectors of diabetic eyes compared to normal eyes ( P < 0.05 ). The retinal nerve fiber layer (RNFL) was significantly thinner in the temporal quadrant ( P < 0.001 ) of diabetic eyes compared to normal eyes. Pearson correlation coefficient analysis showed a significant positive correlation between vessel density and RNFL thickness in the peripapillary region in the temporal (r = 0.468, P < 0.01 ) and superior (r = 0.612, P < 0.01 ) sectors. Multiple linear regression analysis showed that glycated hemoglobin (HbA1c) (β = −1.50, P < 0.01 ) and the duration of diabetes (β = −0.33, P = 0.03 ) were associated with peripapillary vessel density. Conclusions. Preclinical DR presented optic disc microcirculation changes. Temporal RNFL thinning is an early sign of retinal neurodegeneration and is associated with temporal peripapillary vessel density reduction. The duration of diabetes and HbA1c are risk factors for peripapillary vessel density reduction in patients with preclinical DR.

Neurodegeneration plays a significant role in the complex pathology of diabetic retinopathy. Evidence suggests the onset of neurodegeneration occurs early on in the disease, and so a greater understanding of the process is essential for prompt detection and targeted therapies. Neurodegeneration is a common pathway of assorted processes, including activation of inflammatory pathways, reduction of neuroprotective factors, DNA damage, and apoptosis. Oxidative stress and formation of advanced glycation end products amplify these processes and are elevated in the setting of hyperglycemia, hyperlipidemia, and glucose variability. These key pathophysiologic mechanisms are discussed, as well as diagnostic modalities and novel therapeutic avenues, with an emphasis on recent discoveries. The aim of this article is to highlight the crucial role of neurodegeneration in diabetic retinopathy and to review the molecular basis for this neuronal dysfunction, its diagnostic features, and the progress currently made in relevant therapeutic interventions.

Background. Autosomal dominant retinitis pigmentosa (adRP) is a rare cause of progressive visual impairment in young patients and is frequently a result of RHO gene mutations. p.Thr58Arg rhodopsin mutation leads to misfolding of rhodopsin, subsequent accumulation in the endoplasmic reticulum, and leads to consecutive atrophy of photoreceptor cells through apoptosis. Materials and Methods. We describe multimodal imaging findings in a 58-year-old female with adRP due to a c.173 C > G, p.Thr58Arg rhodopsin mutation (confirmed on genotyping), including ultra-wide-field fundus autofluorescence (UWF-FAF), color scanning laser ophthalmoscopy, structural optical coherence tomography (OCT), OCT-angiography (OCT-A), electroretinography (ERG), and visual field testing (HVF). Additionally, we compare the patient’s phenotypic findings to those of her offspring, who was also affected by adRP. Results. The 58-year-old female and her son with symptoms of nyctalopia and decreased vision showed macular pigmentary changes in a bull’s-eye pattern along with bone spicules in periphery with retinal atrophy. Genotyping confirmed p.Thr58Arg rhodopsin mutation. Wide area of dystrophic retina was noted on UWF-FAF, along with corresponding atrophy of photoreceptor layer on OCT. OCTA revealed complete nonperfusion of the superficial capillary plexus in areas of retinal dystrophy. ERG revealed increased latency and decreased amplitudes; HVF revealed constriction of visual fields consistent with retinal findings. Conclusions. Multimodal imaging is extremely helpful in delineating the extent of retinal dystrophy and comparable to ERG for monitoring of progress in retinitis pigmentosa. Photoreceptor layer thickness (measured with OCT) strongly correlated with ERG and can be used as a secondary surrogate for monitoring the disease progress.

Purpose. To measure the macular retinal vessel density (VD) and peripapillary retinal nerve fiber layer (RNFL) in primary angle-closure suspects (PACS) by Angio-OCT to be compared with normal subjects. Methods. Primary angle-closure suspect patients and normal subjects were enrolled in this study. The demographic and clinical characteristics of all subjects, such as RNFL thickness, retinal vessel density, and ocular perfusion pressure, were compared. Results. No significant difference was found in both groups on age, sex distribution, intraocular pressure (IOP), and retinal vessel density. The PACS group exhibited significantly thicker RNFL thickness compared with the control group. The deep vessel density was negatively associated with age ( P = − 0.034 ), while IOP had negative association with ACD ( P = − 0.019 ). OPP was independently associated with RNFL ( B = 0.334 , P = 0.038 ) in the PACS group. Conclusions. OCTA showed significant thicker change on RNFL in the PACS group. Only OPP was independently associated with RNFL in the PACS group.

Purpose. To evaluate the change in intraocular pressure (IOP), central corneal thickness (CCT), axial length, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular ganglion cell complex (GCC) thickness after small incision lenticule extraction (SMILE) surgery. Methods. This prospective observational study was conducted in Espace Nouvelle Vision, Ophthalmological Clinic, Paris, France. Fifty eyes of 25 patients were enrolled in this study and underwent SMILE surgeries. IOP, central corneal thickness (CCT), axial length (AL), peripapillary RNFL thickness, and macular GCC thickness were measured before and at 3 months after SMILE. Results. The mean preoperative spherical equivalent was −3.15 ± 1.50 diopters (D), and the mean postoperative value was 0.15 ± 0.28 D. After SMILE surgery, IOP decreased from 15.03 ± 2.79 mmHg to 11.02 ± 2.73 mmHg and 10.02 ± 2.21 mmHg at 1 and 3 months, respectively ( P < 0.01 for both comparisons). The mean decrease in measured IOP as a function of ablation depth was 0.065 ± 0.031 mmHg/μm. CCT decreased from 545.98 ± 26.61 μm to 478.40 ± 30.26 μm after SMILE surgery ( P < 0.01 ). AL decreased from 24.80 ± 0.84 mm to 24.70 ± 0.83 mm ( P < 0.01 ). There was no statistically significant change in mean peripapillary RNFL or mean GCC thickness after SMILE surgery. Conclusions. SMILE surgery modified IOP measurement, CCT, and AL but did not change peripapillary RNFL and macular GCC thicknesses. The postoperative drop in measured IOP might be explained by the decreased CCT. An accurate re-evaluation of AL should be performed before cataract surgery among post-SMILE patients.

OBJECTIVE To assess the influence of thyroid hormones status and coexistence of autoimmune thyroiditis on optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) results in children with Type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS In the prospective, observational study (n = 175) we analyzed the impact of thyroid hormones on OCT results and the differences between the matched groups of children with T1D (n = 84; age = 13.14 ± 3.6; diabetes duration = 5.99 ± 3.3 years) and the children with T1D and autoimmune thyroiditis (AT) (n = 20; age = 13.94 ± 3.6; diabetes duration = 6.7 ± 4 years). We analyzed the following parameters: fovea avascular zone (FAZ), foveal thickness (FT), parafoveal thickness (PFT), ganglion cell complex (GCC), loss volume (global-GLV, focal-FLV), capillary vessel density: superficial (whole-wsVD, foveal-fsVD, parafoveal-psVD), and deep (whole-wdVD, foveal-fdVD, parafoveal-pdVD. The differences between the groups were tested by the unpaired t-Student test, Mann-Whitney U test as appropriate, whereas p level .05 was recognized as significant. RESULTS We detected the significant correlations between thyroid-stimulating hormone (TSH) level and PFT (r = -0.14; p

Purpose. Retinal nerve fibre layer (RNFL) is a sensitive structure, which is affected by anaemia due to hypoxia. A timely detection of RNFL thinning may aid preventing devastating complications. Optical coherence tomography (OCT) measures RNFL thinning with accuracy and helps in detecting thinning of the retinal layer in anaemic patients. This study was destined to evaluate thinning of RNFL in anaemic patients and their correlation with the haemoglobin level. Methods. It was a prospective comparative study. Total of 151 patients were included in this study. Patients with retinal diseases were excluded from this study. After initial evaluation, haematological and ophthalmological parameters were measured. RNFL was measured with OCT and corroborated with the Hb level and analysed accordingly. EPI and SPSS softwares were used for detail analysis and the correlation between RNFL thinning and the Hb level. Initially, each eye was separately assigned a value (0, 1, and 2) (normal, borderline, and abnormal, respectively) as per the severity of thinning, and then, the sum of the scores of both eyes were considered as a separate variable, and a multiple linear regression analysis was performed with the independent variables. Results. RNFL thinning was found to be significant in each group of patients. There was a strong correlation of RNFL thinning with degree of anaemia. Conclusions. Thalassaemia, iron deficiency anaemia, and anaemia of chronic diseases are associated with the significant damage to RNFL. Degree of anaemia is the most important parameter for such thinning of the RNFL layer.

Background. This meta-analysis is aimed at assessing the peripapillary vessel density (VD) and structural outcomes using optical coherence tomography angiography (OCTA) in patients with nonarteritic anterior ischemic optic neuropathy (NAION). Methods. A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases for literature comparing VD and structural outcomes in patients with NAION and controls was performed. Mean differences (MDs) and its 95% confidence interval (CI) were calculated for continuous estimates. Review Manager (V5.30) was used for analysis. Results. Fourteen published studies met the requirement. The radial peripapillary capillary (RPC) whole enface VD measured by OCTA was significantly lower in patients with NAION compared to that of the controls ( MD = − 10.51 , P < 0.00001 ). The RPC inside disc VD was significantly decreased in the NAION group than that in the control group ( MD = − 8.47 , P < 0.00001 ). For RPC peripapillary VD, there was a statistically significant difference between patients with NAION and the controls ( MD = − 12.48 , P < 0.00001 ). The peripapillary retinal nerve fibre layer (p-RNFL) thickness was significantly lower in patients with NAION in comparison to the controls ( MD = − 22.18 , P = 0.004 ). The ganglion cell complex (GCC) thickness in the macular zone of NAION patients was remarkably reduced compared to that in the controls ( MD = − 17.18 , P = 0.0002 ). Conclusions. The findings suggested that the peripapillary VD and RNFL thickness were attenuated, and the macular GCC thickness was reduced in patients with NAION. OCTA, in the future, may facilitate the diagnosis and monitoring of patients with NAION.

Retinal neovascularization (RNV) is an important pathological feature of vitreoretinopathy that can lead to severe vision loss. The purpose of this study was to identify the role of ephrin-A5 (Efna5) in RNV and to explore its mechanism. The expression pattern and biological significance of Efna5 were investigated in a mouse model of oxygen-induced retinopathy (OIR). The expression of Efna5 and downstream signaling pathway members was determined by RT-PCR, immunofluorescence, immunohistochemistry, and western blot analyses. shRNA was used to knockdown Efna5 in the retina of the OIR mouse model. Retinal flat mounts were performed to evaluate the impact of Efna5 silencing on the RNV process. We found that the Efna5 was greatly upregulated in the retina of OIR mice. Elevated Efna5 mainly colocalized with the retinal vessels and endothelial cells. We then showed that knockdown of Efna5 in OIR mouse retinas using lentivirus-mediated shRNA markedly decreased the expression of Efna5 and reduced the retinal neovascularization and avascular retina area. We further showed hypoxia stimulation dramatically increased both total and phosphorylation levels of ERK1/2 and the phosphorylation levels of Akt in OIR mice. More importantly, knockdown of Efna5 could inhibit the p-Akt and p-ERK signaling pathways. Our results suggested that Efna5 may regulate the RNV. This study suggests that Efna5 was significantly upregulated in the retina of OIR mice and closely involved in the pathological retinal angiogenesis.

Purpose. To highlight the advantages of optical coherence tomography angiography (OCTA) in delineating the morphological features of the retinal and choroidal vascular network during acute, relapsing, and quiescent stages of macular toxoplasma retinochoroiditis. Methods. This prospective study included patients presenting with both active and quiescent ocular toxoplasmoses. OCTA was obtained to diagnose and follow the subsequent vascular network changes at diagnosis and six months after acute presentation. Results. Twenty-three eyes of 23 patients were included. In active lesions, OCTA showed extensive, well-delineated areas of intense hyposignal and perifoveal capillary arcade disruption in the parafoveal superficial capillary plexus (pSCP) and less extensive hyposignal in the parafoveal deep capillary plexus (pDCP). Signals of decreased deep capillary density and disorganization were also seen in the choroid. In nonactive lesions, OCTA demonstrated a homogenous and equally attenuated grayish hyposignal of the pSCP and pDCP and a partial restoration of the nonperfused choroidal areas. Conclusion. OCTA is a useful technique for vascular network analysis in toxoplasma retinochoroiditis. It allows the visualization of the different network changes and behaviors during the different stages of the infection.

The purpose of this study was to evaluate the long-term effects of half-time photodynamic therapy (PDT) on the retinal sensitivity in eyes with chronic central serous chorioretinopathy (CSC). Twenty-two eyes of 22 patients with chronic CSC were studied. PDT was applied with full-dose verteporfin and half-time laser duration. The best-corrected visual acuity (BCVA) and retinal sensitivity in the central 2 and 10 degrees were evaluated at the baseline, and at 12 and 24 months after the half-time PDT. The retinal sensitivity was determined by Macular Integrity Assessment microperimetry (MAIA, Centervue, Padova, Italy). The results showed that the mean retinal sensitivities in the central 2 and 10 degrees were significantly improved at 12 months (25.6±2.79 dB, median; 26.11 dB, 25.6±2.25 dB, median; 25.65 dB, respectively; P<0.001) and at 24 months (26.3±2.62 dB, median; 27.38 dB, 26.6±2.21 dB, median; 27.45 dB, respectively; P<0.001) after the treatment compared to that at the baseline (19.2±3.93 dB, median; 19.34 dB, 20.9±2.92 dB, median; 20.9 dB, respectively). The BCVA was also significantly improved from 0.18±0.19 median; 0.15 logarithm of the minimum angle of resolution (logMAR) units at the baseline to 0.07±0.15 median; 0 logMAR units at 12 months (P<0.001) and to 0.049±0.16 median; -0.039 logMAR units at 24 months (P<0.001). We conclude that half-time PDT results in a significant improvement of the mean central retinal sensitivity for at least 24 months in eyes with chronic CSC. Thus, half-time PDT is beneficial in resolving chronic CSC for a relatively long period.

Purpose. We aimed at reminding that X-linked retinoschisis may also be seen in female patients and share our vitreoretinal surgical experience. Methods. The patient underwent pars plana vitrectomy including the closure of the macular holes with inverted ILM flap technique bilaterally. Lens extractions were performed by phacoemulsification during the removal of silicone oil endotamponade. Patient. An 18-year-old girl with X-linked retinoschisis and large macular holes in both eyes presented to the clinic of ophthalmology. It was confirmed that the patient had RS1 mutation Results. Nine-month-follow-up was uneventful for retinal findings. Significant improvement in visual acuity was achieved, and macular holes were remained closed. Conclusion. In cases with large macular holes due to XLR, an inverted ILM flap technique might be safe and effective. Four-month-silicone-endotamponade might be sufficient.

Purpose. Adenosine A2A receptor (A2AR) signaling is neuroprotective in some retinal damage models, but its role in neuronal survival during retinal detachment (RD) is unclear. We tested the hypothesis that A2AR antagonist ZM241385 would prevent photoreceptor apoptosis by inhibiting retinal inflammation and oxidative stress after RD. Methods. The A2AR antagonist ZM241385 was delivered daily to C57BL/6J mice for three days at a dose (3 mg/kg, i.p.) starting 2 hours prior to creating RD. A2AR expression, microglia proliferation and reactivity, glial fibrillary acidic protein (GFAP) accumulation, IL-1β expression, and reactive oxygen species (ROS) production were evaluated with immunofluorescence. Photoreceptor TUNEL was analyzed. Results. A2AR expression obviously increased and accumulated in microglia and Müller cells in the retinas after RD. The A2AR antagonist ZM241385 effectively inhibited retinal microglia proliferation and reactivity, decreased GFAP upregulation and proinflammatory cytokine IL-1β expression of Müller cells, and suppressed ROS overproduction, resulting in attenuation of photoreceptor apoptosis after RD. Conclusions. The A2AR antagonist ZM241385 is an effective suppressor of microglia proliferation and reactivity, gliosis, neuroinflammation, oxidative stress, and photoreceptor apoptosis in a mouse model of RD. This suggests that A2AR blockade may be an important therapeutic strategy to protect photoreceptors in RD and other CNS diseases that share a common etiology.

Inhibitors of dipeptidyl peptidase-4 (DPP-4) are widely used to treat diabetes mellitus, but data concerning their effects on the barrier stability of retinal endothelial cells (REC) in vivo and in vitro are inconsistent. Therefore, we studied whether the barrier properties of immortalized endothelial cells of the bovine retina (iBREC) were affected by the inhibitors of DPP-4 sitagliptin (10-1000 nM) and diprotin A (1-25 μM). Their effects were also investigated in the presence of VEGF-A165 because diabetic patients often develop macular edema caused by VEGF-A-induced permeability of REC. To detect even transient or subtle changes of paracellular and transcellular flow as well as adhesion of the cells to the extracellular matrix, we continuously monitored the cell index (CI) of confluent iBREC grown on gold electrodes. Initially, the CI remained stable but started to decline significantly and persistently at 40 h or 55 h after addition of sitagliptin or diprotin A, respectively. Both inhibitors did not modulate, prevent, or revert the persistent VEGF-A165-induced reduction of the CI. Interestingly, sitagliptin and diprotin A increased the expression of the tight-junction protein claudin-1 which is an important component of a functional barrier formed by iBREC. In contrast, expressions of CD29—a subunit of the fibronectin receptor—or of the tetraspanin CD9 were lower after extended treatment with the DPP-4 inhibitors; less of the CD9 was seen at the plasma membrane after prolonged exposure to sitagliptin. Because both associated proteins are important for adhesion of iBREC to the extracellular matrix, the observed low CI might be caused by weakened attachment of the cells. From our results, we conclude that extended inhibition of DPP-4 destabilizes the barrier formed by microvascular REC and that DPP-4 inhibitors like sitagliptin do not counteract or enhance a VEGF-A165-induced barrier dysfunction as frequently observed in DME.

Retinal hemorrhaging (RH) is indicative and prevalent in abusive head trauma (AHT)—yet the direct cause of the RH from AHT is unknown. Our hypothesis is that RH in AHT is the combination of shaking forces and hypertension. This combination of effects explains why RH is not normally observed in common childhood accidents but is nearly exclusively observed in AHT. An experimental model using porcine eyes was designed to ascertain the required pressure change for sudden RH and, via a computer model, the subsequent stress increase in blood vessels. The porcine eyes were cannulated via the maxillary artery and pressurized until perfusion and RH were observed. Fluid was injected into the head with a computer-controlled continuous flow syringe pump; video of the fundus was recorded during perfusion; and the pressure of the fluid entering the eye was recorded as well. A computer model was created in COMSOL to simulate loading from hypertension, shaking, and the combination of the forces. This model was validated via experimental data collected from the porcine model. It was found that hypertension or shaking alone did not cause an increase in stress required to cause RH. But when the loading of shaking and hypertension was combined, as would occur in AHT, the stress increases were greater than those extrapolated from the porcine model and would cause RH.

The feature extraction stage remains a major component of every biometric recognition system. In most instances, the eventual accuracy of a recognition system is dependent on the features extracted from the biometric trait and the feature extraction technique adopted. The widely adopted technique employs features extracted from healthy retinal images in training retina recognition system. However, literature has shown that certain eye diseases such as diabetic retinopathy (DR), hypertensive retinopathy, glaucoma, and cataract could alter the recognition accuracy of the retina recognition system. This connotes that a robust retina recognition system should be designed to accommodate healthy and diseased retinal images. A framework with two different approaches for retina image recognition is presented in this study. The first approach employed structural features for healthy retinal image recognition while the second employed vascular and lesion-based features for DR retinal image recognition. Any input retinal image was first examined for the presence of DR symptoms before the appropriate feature extraction technique was adopted. Recognition rates of 100% and 97.23% were achieved for the healthy and DR retinal images, respectively, and a false acceptance rate of 0.0444 and a false rejection rate of 0.0133 were also achieved.

Diabetic retinopathy (DR) is one of the hallmark complications of diabetes and a leading cause of vision loss in adults. Retinal pericyte death seems to be a prominent feature in the onset of DR. Pyroptosis is an inflammatory form of programmed cell death, defined as being caspase-gasdermin-D (GSDMD)-dependent. The NOD-like receptor pyrin 3 (NLRP3) inflammasome plays an important role in mediating GSDMD activation. However, the role and mechanism of pyroptosis in the loss of retinal pericytes during the pathogenesis of DR are still unclear. In the present study, we cultured primary human retinal pericytes (HRPs) in high glucose medium; caspase-3 inhibitor DEVD, caspase-1 inhibitor YVAD, or NLRP3 inhibitor glyburide was used as intervention reagents; GSDMD was overexpressed or suppressed by transfection with an expressing vector or retroviral silencing of GSDMD, respectively. Our data showed that high glucose induced NLRP3-caspase-1-GSDMD activation and pore formation in a dose- and time-dependent manner (p<0.05) and resulted in the inflammatory cytokines IL-1β and IL-18 and lactate dehydrogenase (LDH) release from HRPs (p<0.05), which are all signs of HRP pyroptosis. Overexpression of GSDMD facilitated high glucose-induced pyroptosis (all p<0.05). However, these effects were blunted by synergistically treating DEVD, YVAD, and silencing GSDMD (p<0.05). Taken together, our results firstly revealed that high glucose induced the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis.

In the field of ophthalmology, diabetic retinopathy (DR) is a major cause of blindness. DR is based on retinal lesions including exudate. Exudates have been found to be one of the signs and serious DR anomalies, so the proper detection of these lesions and the treatment should be done immediately to prevent loss of vision. In this paper, pretrained convolutional neural network- (CNN-) based framework has been proposed for the detection of exudate. Recently, deep CNNs were individually applied to solve the specific problems. But, pretrained CNN models with transfer learning can utilize the previous knowledge to solve the other related problems. In the proposed approach, initially data preprocessing is performed for standardization of exudate patches. Furthermore, region of interest (ROI) localization is used to localize the features of exudates, and then transfer learning is performed for feature extraction using pretrained CNN models (Inception-v3, Residual Network-50, and Visual Geometry Group Network-19). Moreover, the fused features from fully connected (FC) layers are fed into the softmax classifier for exudate classification. The performance of proposed framework has been analyzed using two well-known publicly available databases such as e-Ophtha and DIARETDB1. The experimental results demonstrate that the proposed pretrained CNN-based framework outperforms the existing techniques for the detection of exudates.

Objective. To evaluate the role of CCAAT/enhancer-binding protein β (C/EBP β) in retinal neovascularization (RNV) in an oxygen-induced retinopathy (OIR) model. Methods. Rats with OIR were exposed to alternating hypoxic and hyperopic conditions for 14 days. Then, the rats with OIR were assigned randomly to groups that received intravitreal injections of either shRNA lentiviral particles targeting C/EBP β (LV.shC/EBP β) or control particles (LV.shScrambled). The effectiveness of transduction using intravitreal injection of C/EBP β shRNA was examined in rats with OIR. The retinal vascular damage and accumulation of RNV were determined by retinal fluorescein-dextran perfusion, retinal ADPase staining, and periodic acid-Schiff (PAS) staining. Retinal function was recorded by electroretinogram responses to full-field light flashes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analyses were used to measure mRNA and protein levels of C/EBP β and vascular endothelial growth factor (VEGF). The expression of p-C/EBP β was also examined by western blot analyses. The location of C/EBP β expression in the retina was determined by immunohistochemistry. Results. In OIR rats, the expression levels of C/EBP β and VEGF were significantly increased at both the mRNA and protein levels (P<0.01). The p-C/EBP β expression was consistent with the level of C/EBP β. C/EBP β was predominantly localized to the ganglion cell layer (GCL) and the inner nuclear layer (INL). The retinal C/EBP β level was significantly reduced in tissues from rats with OIR transduced with LV.shC/EBP β compared with tissues from those transduced with LV.shScrambled (P<0.01). Compared with those of the rats with OIR in the LV.shScrambled group, nonperfused retinal areas, neovascular tufts, pericyte death, and the ratio of endothelial cells to pericytes in the LV.shC/EBP β group were significantly reduced. In OIR rats, retinal function was impaired. There was no significant change in retinal dysfunction between the LV.shC/EBP β group and the LV.shScrambled group. The levels of VEGF mRNA and protein in the LV.shC/EBP β group were also decreased significantly compared with those of the rats with OIR in the LV.shScrambled group (P<0.01). Conclusions. C/EBP β shRNA inhibits RNV in OIR. A potential mechanism may be that the activity of C/EBP β increases with its overexpression, which in turn aggravates the amount of the retinal vascular damage and promotes transcription of VEGF. C/EBP β might be a new therapeutic target for preventing RNV.

The aim of this study was to analyze the efficacy of micropulse laser treatment (MLT) compared with the continuous-wave laser (CL) in treating eyes with chronic central serous chorioretinopathy (CSC) in a 12-month follow-up study. Methods: A retrospective observational study included 51 eyes with chronic CSC; 35 eyes were treated with MLT (Group A), and 16 eyes were treated with CL (Group B). We analyzed the best corrected visual acuity (BCVA) and retinal microstructural changes in spectral optical coherence tomography before the treatment, one and twelve months after the laser procedure. Results: The final mean BCVA was 0.89 ± 0.13 in Group A and 0.71 ± 0.17 in Group B. Photoreceptor length decreased significantly in both groups and amounted 61.2 μm in Group A and 42.9 μm in Group B one year after the treatment. Complete absorption of subretinal fluid twelve months after the laser procedure was noted in 74.3% eyes in Group A and in 87.5% eyes in group B. Hyper-reflective subretinal deposits were observed in 10/35 eyes in Group A but in 15/16 eyes in Group B on the final follow-up visit. Conclusion. MLT-treated patients showed better functional and microstructural results than patients treated with CL.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia, excessive fibrosis of skin and internal organs, and angiogenesis imbalance. The aim of the study was to evaluate in SSc patients the association between the retinal microcirculation disturbances and the presence of peripheral trophic changes and to determine the role of angiogenesis factors in the formation of vascular changes in scleroderma. Twenty-five SSc patients and 25 age- and sex-matched healthy controls were included to the study. Assay of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears was done for all patients and controls using enzyme-linked immunosorbent assay. Retinal blood circulation was investigated with fluorescein angiography (FA) in the SSc patients only. In our research, proportion of mainly hypertensive patients presenting with a large spectrum of retinal microvascular lesions was 72%, while proportion of patients with skin microvascular lesions within distal phalanxes of fingers and toes was 76%. We noticed that patients with pathological changes in the FA examination had finger ulcerations significantly more often than patients without changes in the eye fundus. There were no statistically significant differences in the serum concentration of VEGF and sVEGFR2 between subjects in both analyzed groups. Analysis of lower levels of VEGF (p=<0.001) and sVEGFR-2 (p=<0.001) in blood serum accompanied by simultaneous higher levels of VEGF/sVEGFR-2 ratio in tears of SSc patients, as compared with the control group, indicates the superiority of proangiogenic factors in patients’ tears.

Mosaicking of retinal images is potentially useful for ophthalmologists and computer-aided diagnostic schemes. Vascular bifurcations can be used as features for matching and stitching of retinal images. A fully convolutional network model is employed to segment vascular structures in retinal images to detect vascular bifurcations. Then, bifurcations are extracted as feature points on the vascular mask by a robust and efficient approach. Transformation parameters for stitching can be estimated from the correspondence of vascular bifurcations. The proposed feature detection and mosaic method is evaluated on retinal images of 14 different eyes, 62 retinal images. The proposed method achieves a considerably higher average recall rate of matching for paired images compared with speeded-up robust features and scale-invariant feature transform. The running time of our method was also lower than other methods. Results produced by the proposed method superior to that of AutoStitch, photomerge function in Photoshop cs6 and ICE, demonstrate that accurate matching of detected vascular bifurcations could lead to high-quality mosaic of retinal images.

Retinal organoid technology enables generation of an inexhaustible supply of three-dimensional retinal tissue from human pluripotent stem cells (hPSCs) for regenerative medicine applications. The high similarity of organoid-derived retinal tissue and transplantable human fetal retina provides an opportunity for evaluating and modeling retinal tissue replacement strategies in relevant animal models in the effort to develop a functional retinal patch to restore vision in patients with profound blindness caused by retinal degeneration. Because of the complexity of this very promising approach requiring specialized stem cell and grafting techniques, the tasks of retinal tissue derivation and transplantation are frequently split between geographically distant teams. Delivery of delicate and perishable neural tissue such as retina to the surgical sites requires a reliable shipping protocol and also controlled temperature conditions with damage-reporting mechanisms in place to prevent transplantation of tissue damaged in transit into expensive animal models. We have developed a robust overnight tissue shipping protocol providing reliable temperature control, live monitoring of the shipment conditions and physical location of the package, and damage reporting at the time of delivery. This allows for shipping of viable (transplantation-competent) hPSC-derived retinal tissue over large distances, thus enabling stem cell and surgical teams from different parts of the country to work together and maximize successful engraftment of organoid-derived retinal tissue. Although this protocol was developed for preclinical in vivo studies in animal models, it is potentially translatable for clinical transplantation in the future and will contribute to developing clinical protocols for restoring vision in patients with retinal degeneration.