WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy.

BACKGROUND: In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR. METHOD: Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting. RESULT: Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability. CONCLUSIONS: WIF1 exerts an inhibitory effect on the Wnt/ß-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.

Alterations in Macular Microvasculature in Pterygium Patients Measured by OCT Angiography.

Previous studies have reported an association between pterygia and maculopathy, yet the underlying mechanisms and alterations to the macular microvasculature in pterygium patients have yet to be fully elucidated. Our study conducted an analysis of macular superficial vessel length density (VLD) and vessel perfusion density (VPD) to establish associations between the conjunctival and macular microvasculature in patients with unilateral and bilateral pterygia. We revealed a loss of macular microvasculature in the outer nasal (ON) region in both unilateral and bilateral pterygium patients. VLD was significantly decreased in both pterygium groups in the ON region, and VPD was notably lower in bilateral pterygium patients in the same area. Furthermore, in unilateral pterygium patients, the vessel percent pixel coverage (PPC) of the pterygium and the area of the pterygium exhibited a negative correlation with VLD in the ON region. Multiple stepwise linear regression models indicated that the PPC could best predict VLP in the ON region. Taken together, our findings suggest that patients with pterygia may be more susceptible to macular diseases, and this may be due to a compensatory increase in blood perfusion via the anterior ciliary artery. These results underscore the importance of managing maculopathy in patients with pterygia.

Optimized design of surgical steps in pars plana vitrectomy for macular hole retinal detachment in pathological myopia decreases rate of iatrogenic retinal break and shortens length of operation.

BACKGROUND: To investigate the effect of surgical steps optimization in pars plana vitrectomy (PPV) with internal limiting membrane (ILM) flap for macular hole retinal detachment (MHRD) in pathological myopia. METHODS: A retrospective, consecutive, nonrandomized comparative study. High myopic eyes diagnosed with MHRD receiving PPV with ILM flap from March 2019 to June 2020 in Department of Ophthalmology, Xiangya Hospital, Central South University were included in the study. Patients were included into two groups based on different design of surgical steps. In the routine group, extension of posterior vitreous detachment (PVD) towards periphery was performed right after induction of PVD. In the experiment group, the retina was reattached with drainage of subretinal fluid through macular hole before peripheral vitreous was dealt with. Complete ophthalmic examinations were performed before and after surgery. The follow-up time was at least 6 months. The rate of iatrogenic retinal break and length of operation were compared between the two groups. RESULTS: Thirty-one eyes from 31 patients were included in the study with 15 in the experiment group and 16 in the routine group. Demographics showed no statistically significant difference between the two groups. Post-op BCVA, rate of macular hole closure and rate of retinal reattachment were similar in the two groups. The rate of iatrogenic retinal break in the experiment group was significantly lower than that in the routine group (6.7% vs. 37.5%, P < 0.05). The average length of operation was 78.6 ± 18.8 min in the routine group and 64.0 ± 12.1 min in the experiment group (P < 0.05). CONCLUSIONS: Optimized design of surgical steps in PPV for MHRD could effectively decrease the rate of iatrogenic retinal tear and shorten the length of operation.

Machine learning based on Optical Coherence Tomography images as a diagnostic tool for Alzheimer's disease.

AIMS: We mainly evaluate retinal alterations in Alzheimer's disease (AD) patients, investigate the associations between retinal changes with AD biomarkers, and explore an optimal machine learning (ML) model for AD diagnosis based on retinal thickness. METHODS: A total of 159 AD patients and 299 healthy controls were enrolled. The retinal parameters of each participant were measured using optical coherence tomography (OCT). Additionally, cognitive impairment severity, brain atrophy, and cerebrospinal fluid (CSF) biomarkers were measured in AD patients. RESULTS: AD patients demonstrated a significant decrease in the average, superior, and inferior quadrant peripapillary retinal nerve fiber layer, macular retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL) thicknesses, as well as total macular volume (TMV) (all p < 0.05). Moreover, TMV was positively associated with Mini-Mental State Examination and Montreal Cognitive Assessment scores, IPL thickness was correlated negatively with the medial temporal lobe atrophy score, and the GCL thickness was positively correlated with CSF Aß42 /Aß40 and negatively associated with p-tau level. Based on the significantly decreased OCT variables between both groups, the XGBoost algorithm exhibited the best diagnostic performance for AD, whose four references, including accuracy, area under the curve, f1 score, and recall, ranged from 0.69 to 0.74. Moreover, the macular retinal thickness exhibited an absolute superiority for AD diagnosis compared with other enrolled variables in all ML models. CONCLUSION: We identified the retinal alterations in AD patients and found that macular thickness and volume were associated with AD severity and biomarkers. Furthermore, we confirmed that OCT combined with ML could serve as a potential diagnostic tool for AD.

Wnt inhibitory factor 1 ameliorated diabetic retinopathy through the AMPK/mTOR pathway-mediated mitochondrial function.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and will lead to visual impairment. We aim to explore the effects and mechanisms of wnt inhibitory factor 1 (WIF1) in the progression of DR. To establish DR in vitro and in vivo, human retinal pigment epithelium (RPE) cell line ARPE-19 was treated with high-glucose (HG) and diabetic mice models were induced by streptozotocin (STZ), respectively. Different dose of recombinant WIF1 protein was used to treat DR. qRT-PCR and western blotting results demonstrated that WIF1 was downregulated, while VEGFA was upregulated in HG-induced ARPE-19 cells. WIF1 overexpression promoted cell migration. The ARPE-19 cells culture medium treated with WIF1 inhibited retinal endothelial cell tube formation and downregulated VEGFA expression. Moreover, WIF1 decreased the levels of ROS and MDA, while increasing the activity of SOD and GPX. WIF1 increased the ΔΨm in the mitochondria and downregulated the expression of mitochondrial autophagy-related proteins including Parkin, Pink1, LC3-II/LC3-I ratio, cleaved caspase 3, and cyt-c, which ameliorated mitochondrial dysfunction. The in vivo studies further demonstrated the consistent effects of WIF1 in STZ-induced mice. Taken together, WIF1 ameliorated mitochondrial dysfunction in DR by downregulating the AMPK/mTOR pathway.

Inverted multi-layer internal limiting membrane flap for macular hole retinal detachment in high myopia.

To investigate the surgical outcomes of pars plana vitrectomy (PPV) combined with inverted multi-layer internal limiting membrane (ILM) flap for the treatment of macular hole retinal detachment in high myopia. We retrospectively analysed the medical records of macular hole retinal detachment (MHRD) patients with high myopia. The patients were divided into two groups with different surgical procedure: inverted multi-layer ILM flap group (group 1, 27 eyes) and the ILM peeling group (group 2, 29 eyes). Retinal reattachment rate, macular hole closure rate at last follow-up and BCVA at 6 months post-operation were compared between the two groups. After primary PPV and silicone oil removal, the retinal reattachment rate was 96.3% in group 1 and 93.1% in group 2 respectively at last follow-up, showing no statistically significant difference (odds ratio = 0.525, P = 1.000). All eyes in group 1 had type I macular closure (100%, 27/27), while only 7 eyes (24.1%, 7/29) in group 2 have type I macular hole closure. The difference was statistically significant (odds ratio = 0, P < 0.05). The mean logMAR BCVA both improved significantly at 6 months post-operation compared with pre-operation (t = 4.181, P < 0.001; t = 3.217, P < 0.001), however the difference of post-operation BCVA between the two groups was not statistically significant (t = 0.906, P > 0.05). PPV combined with inverted multi-layer ILM flap could achieve better anatomical outcomes than ILM peeling technique with no significant advantage in functional outcomes.

Retinal Microvascular Density Was Associated With the Clinical Progression of Parkinson's Disease.

BACKGROUND: Retinal microvascular density has been studied in neurodegenerative diseases, whereas patients with Parkinson's disease (PD) at different clinical stages have been rarely investigated. The present study aimed to evaluate the microvascular variations in superficial retinal capillary plexus (SCP) in patients with PD on different Hoehn-Yahr (H-Y) stages by optical coherence tomography angiography (OCTA), as well as determine their relationships with clinical parameters. METHODS: In total, 115 patients with PD and 67 healthy controls (HCs) were recruited. The PD group was divided into three groups based on the H-Y stage. The OCTA examination was performed in all participants, and the macular vessel density (m-VD), peripapillary vessel density (p-VD), and foveal avascular zone (FAZ) area were measured. RESULTS: The m-VD in all regions, p-VD in center [6.1 (4.8, 6.95) mm-1 in healthy eyes vs. 5.1 (3.7, 6.4) mm-1 in patients], nasal inner (NI) [18.5 (17.8, 19.3) mm-1 in healthy eyes vs. 17.9 (17.1, 18.7) mm-1 in patients], temporal outer (TO) [19.6 (18.9, 20.2) mm-1 in healthy eyes vs. 19.3 (18.5, 19.7) mm-1 in patients] regions and FAZ area [0.36 (0.32, 0.39) mm2 in healthy eyes vs. 0.29 (0.26, 0.33) mm2 in patients] noticeably decreased in PD groups compared with HC (p < 0.05). Moreover, the FAZ area was suggested to decline significantly in patients with PD with H-Y I stage (p < 0.05), while it was more serious in the H-Y III stage in patients. Furthermore, we found that m-VD exhibited a significant negative correlation with age, disease duration, UPDRS scores, NMSS scores, and H-Y stage. CONCLUSION: OCTA has the potential to non-invasively detect the microvascular changes in patients with PD with different clinical stages in vivo, and it may be a valuable tool to monitor the PD progression.

Wnt inhibitory 1 ameliorates neovascularization and attenuates photoreceptor injury in an oxygen-induced retinopathy mouse model.

Retinal neovascularization (RNV) associated diseases typically exhibit pathological neovascularization and neurodegeneration. Wnt inhibitor factor 1 (WIF1) is a secreted Wnt antagonist that regulates angiogenesis. However, the significance of WIF1 in RNV associated disease has not been explicitly tested. In our study, we found that the WIF1 expressions were strongly downregulated in the vitreous of proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). Similarly, retinal WIF1 expression was significantly downregulated in OIR mice, relative to normal mice at P17. After injection of WIF1 overexpression lentivirus into the vitreous of OIR mice, overexpressing WIF1 in OIR mice vitreous strongly reduced avascular areas and neovascular tufts, increased vessel branches, raised a-, b-waves and oscillatory potentials amplitudes on ERG, increased retinal thickness and the number of synapses in retina, normalized the Golgi, mitochondria, and outer segments of photoreceptors. Furthermore, overexpression WIF1 suppressed expressions of ß-catenin, vascular endothelial growth factor (VEGF), p-AKT and p-ERK, reduced retinal reactive oxygen species (ROS) and 4-HNE levels, improved autophagic flux, and mitigated apoptosis. In summary, WIF1 plays a key role in alleviating angiogenesis and in improving visual function in OIR mice by suppressing the Wnt/ß-catenin-VEGF signaling pathway and ROS levels. WIF1 is an excellent candidate for targeted therapy against RNV associated diseases.

First Human Results With the 256 Channel Intelligent Micro Implant Eye (IMIE 256).

Purpose: To report on the safety and efficacy of the 256-channel Intelligent Micro Implant Eye epiretinal prosthesis system (IMIE 256). Methods: The IMIE 256 implants were implanted in the right eyes of five subjects with end-stage retinitis pigmentosa. Following implantation, the subjects underwent visual rehabilitation training for 90 days, and their visual performance was evaluated using the grating visual acuity test, Tumbling E visual acuity test, direction of motion, square localization, and orientation and mobility test. To evaluate the safety of the IMIE 256, all adverse events were recorded. Results: Subjects performed significantly better on all evaluations with the IMIE 256 system on as compared with the performance at baseline or with the system off. There was a steady improvement in performance at each observation interval, indicating that the training and/or practice helped the subjects use the IMIE 256. There were two serious adverse events-electrode array movement and low intraocular pressure in one subject, which resolved with surgery. There were no other adverse events observed except those expected in the course of postoperative healing. Conclusions: These results show an improved safety and efficacy profile compared with that of the Argus II implant. Further clinical trials are needed to confirm these results in a larger number of subjects and over longer durations. Translational Relevance: To our knowledge, this study reports the first in-human data from a high-density (256 electrodes) epiretinal implant to restore sight to a subset of blind patients.

DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice.

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR. METHODS: Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model. DR mouse model was established by streptozotocin injection, and then received 5-Aza-2-deoxycytidine (DAC; DNA methyltransferase inhibitor) treatment. Hematoxylin-eosin staining was performed to assess retinal tissue damage. PPARα methylation was examined by Methylation-Specific PCR. Flow cytometry and DCFH-DA fluorescent probe was used to estimate apoptosis and reactive oxygen species (ROS). The interaction between DNA methyltransferase-1 (DNMT1) and PPARα promoter was examined by Chromatin Immunoprecipitation. Quantitative real-time PCR and western blot were performed to assess gene and protein expression. RESULTS: HG treatment enhanced the methylation levels of PPARα, and repressed PPARα expression in HRCPs. The levels of apoptotic cells and ROS were significantly increased in HRCPs in the presence of HG. Moreover, DNMT1 was highly expressed in HG-treated HRCPs, and DNMT1 interacted with PPARα promoter. PPARα overexpression suppressed apoptosis and ROS levels of HRCPs, which was rescued by DNMT1 up-regulation. In DR mice, DAC treatment inhibited PPARα methylation and reduced damage of retinal tissues. CONCLUSION: DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice. Thus, this study may highlight novel insights into DR pathogenesis.

Posterior pole retinotomy for treatment of recurrent macular hole retinal detachment in highly myopic eyes: a pilot study.

BACKGROUND: To investigate the feasibility and efficacy of posterior pole retinotomy to treat recurrent macular hole retinal detachment (MHRD) in highly myopic patients. METHODS: We performed a retrospective study and reviewed the medical records in our hospital between January 1, 2016 and December 31, 2018. Highly myopic patients who received posterior pole retinotomy with silicone oil tamponade for their recurrent MHRD after pars plana vitrectomy were included in the analysis. Postoperative retinal reattachment, best-corrected visual acuity (BCVA), macular hole closure, and complications were evaluated. RESULTS: There were 11 patients (11 eyes) included in this study. All retinas were reattached. Silicone oil was successfully removed from all eyes 1.5-3 months after the surgery. Macular holes were completely closed in three eyes and remained flat open in eight eyes. The BCVA of all eyes improved significantly at 12 months after surgery (logarithm of the minimal angle of resolution, pre vs. postoperatively, 1.87 ± 0.44 vs. 1.15 ± 0.24, P < 0.05). None of the patients had complications such as endophthalmitis, fundus hemorrhage, retinal redetachment, and proliferative vitreoretinopathy. CONCLUSION: Posterior pole retinotomy is a safe and effective surgery to treat recurrent MHRD after pars plana vitrectomy in highly myopic patients.

Leukemia inhibitory factor protects photoreceptor cone cells against oxidative damage through activating JAK/STAT3 signaling.

BACKGROUND: The present study aimed to investigate the protective role of leukemia inhibitory factor (LIF) against oxidative damage in photoreceptor cone cells. METHODS: In vivo, dark-adapted mice were injected with LIF or phosphate-buffered saline (PBS) intravitreously prior to being exposed to 5,000 lux bright light to determine the protective effect of LIF against light damage in cone cells. Oxidative damage to cone cells was analyzed using electroretinograms, immunostaining, Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR). In vitro, 661W cells were pretreated with 5 ng/mL of LIF with or without 50 µM of signal transducer and activator of transcription 3 (STAT3) inhibitor S3I201 for 1 h prior to treatment with 1 mM H2O2; cell survival, apoptosis, the oxidative stress index, and the activation of STAT3, extracellular signal-regulated kinase (ERK1/2), and AKT were subsequently determined. RESULTS: In vivo, light induction damaged the function and morphology of cone cells, and LIF was observed to protect cone cells from this light damage. Moreover, the activation of the Janus tyrosine kinase (JAK)/STAT3 signaling pathway and the subsequent changes in apoptosis and proliferation-related genes were found to be involved in the protective effect of LIF against light-induced retinal damage. In the H2O2-induced 661W cell model, H2O2 increased cellular apoptosis rates, the expression levels of Bcl-2-associated X-protein (BAX) and cleaved caspase 3, reactive oxygen species (ROS) production, and malondialdehyde content, while decreasing the cell viability, and Bcl-2, superoxide dismutase, catalase, and glutathione peroxidase activity. LIF was observed to block these events; however, the administration of the STAT3 inhibitor S3I201 reversed the beneficial effects of LIF on H2O2-triggered apoptosis and ROS production. CONCLUSIONS: In conclusion, the present study suggested that LIF may relieve oxidative damage in cone cells through suppressing apoptosis and oxidative stress by targeting the STAT3 signaling pathway.

Outcomes of a new 3-D printing-assisted personalized macular buckle combined with para plana vitrectomy for myopic foveoschisis.

PURPOSE: To describe and evaluate the application of a new 3-D printing-assisted personalized macular buckle for patients with myopic foveoschisis (MFS). METHODS: Twelve eyes of 12 patients with MFS were included in this study. Preoperative MRI images were subsequently measured after marker implantation and imported into the MIMICS software for the 3-D reconstruction of a virtual model of an eyeball and a marker. The virtual eyeball model was designed according to the degree of retinoschisis, which was measured using optical coherence tomography preoperatively. A macular buckle was designed using a titanium stent, assisted by 3-D printing; furthermore, it was surgically placed in combination with pars plana vitrectomy. Visual acuity, axial length and anatomic outcomes were analysed pre- and postoperatively. RESULTS: Macular schisis in all patients was completely resolved after the surgery without any postoperative complications. The mean postoperative best corrected visual acuity (LogMAR) improved significantly from 1.21 to 0.92 during the 6-month follow-up period (p < 0.001) and reached 0.9 (p < 0.001) after 2 years. The axial length was significantly shortened during the 2 years postoperatively follow-up period (p < 0.01). The average axial lengths in all patients decreased from 30.62 mm preoperatively to 29.81 mm 1 month postoperatively and remained around 30.16 mm from 1 year after the surgery. CONCLUSION: The 3-D printing technique is useful to predict the indentation height and position of the macular buckle. The 3D-printing-assisted macular buckle, in combination with vitrectomy, is an effective, safe and accurate treatment modality for MFS.

DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR. METHODS: Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model. DR mouse model was established by streptozotocin injection, and then received 5-Aza-2-deoxycytidine (DAC; DNA methyltransferase inhibitor) treatment. Hematoxylin-eosin staining was performed to assess retinal tissue damage. PPARα methylation was examined by Methylation-Specific PCR. Flow cytometry and DCFH-DA fluorescent probe was used to estimate apoptosis and reactive oxygen species (ROS). The interaction between DNA methyltransferase-1 (DNMT1) and PPARα promoter was examined by Chromatin Immunoprecipitation. Quantitative real-time PCR and western blot were performed to assess gene and protein expression. RESULTS: HG treatment enhanced the methylation levels of PPARα, and repressed PPARα expression in HRCPs. The levels of apoptotic cells and ROS were significantly increased in HRCPs in the presence of HG. Moreover, DNMT1 was highly expressed in HG-treated HRCPs, and DNMT1 interacted with PPARα promoter. PPARα overexpression suppressed apoptosis and ROS levels of HRCPs, which was rescued by DNMT1 up-regulation. In DR mice, DAC treatment inhibited PPARα methylation and reduced damage of retinal tissues. CONCLUSION: DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice. Thus, this study may highlight novel insights into DR pathogenesis.

Macular vessel density and foveal avascular zone parameters in patients after acute primary angle closure determined by OCT angiography.

This study analyzed the optical coherence tomography angiography (OCTA) macular parameters in primary angle-closure glaucoma (PACG) patients after acute primary angle closure (APAC) episodes. Thirty-three patients with 33 APAC eyes and 33 primary angle closure suspect (PACS) eyes and 33 age-matched normal subjects (controls) were enrolled. Macular vessel density (VD) in central, inner, outer and full regions and foveal avascular zone (FAZ) parameters (area, perimeter and circularity index) were compared between APAC, PACS, and control eyes. For resolved APAC eyes, the VD in each macular region was significantly lower than that in control eyes, with less central and inner macular VD than PACS eyes. The central macular VD was significantly lower in PACS eyes than in controls. There was no difference in FAZ area and perimeter between APAC, PACS, and control eyes. FAZ circularity was highest in control eyes, followed by PACS eyes, and lowest in APAC eyes. The AUC, sensitivity and specificity of FAZ circularity were 0.944, 93.9% and 84.8%, respectively, in APAC eyes and 0.881, 84.8% and 81.8%, respectively, in PACS eyes. Therefore, FAZ circularity had the best discrimination capability for detecting both APAC and PACS eyes. Macular assessment with OCTA could provide an accurate early-stage diagnostic tool for PACG.

Morphological Characteristics Predict Postoperative Outcomes After Vitrectomy in Myopic Traction Maculopathy Patients.

BACKGROUND AND OBJECTIVES: To provide the surgical indication for patients with myopic traction maculopathy (MTM) by investigating the postoperative outcomes after vitrectomy among different types of morphological characteristic groups. PATIENTS AND METHODS: This was a retrospective cohort study that included patients (37 eyes) diagnosed with MTM at a single institution. All 37 eyes from 37 patients with MTMs were classified into three groups: foveal retinoschisis (FS), lamellar macular hole (LMH), and foveal retinal detachment (FRD). The ratios of anatomic recovery, central retinal thickness (CRT), and best-corrected visual acuity (BCVA) were statistically analyzed among the three groups preoperatively and at 1, 3, 6, and 12 months after vitrectomy. RESULTS: Anatomical recovery could be found in all patients of the FS group at 6 months postoperatively and in the LMH group at 12 months postoperatively. Only 83.33% patients in the FRD group showed anatomic recovery until 12 months. The time taken for CRT to reduce to 200 µm was gradually increased between the FS, LMH, and FRD groups. Postoperative BCVA was better in the FS group than the LMH and FRD groups (P < .05), but the LMH and FDR groups had no difference (P ≥ .05) at any point. The visual acuity was significantly improved in the FS group (P < .01) and FRD group (P = .018), but not in the LMH group (P = .196) at 12 months postoperatively. CONCLUSIONS: The FS group achieved anatomical recovery in the shortest time and had the best postoperative BCVA. FRD patients could get visual gain but need too much time for the anatomical recovery. LMH patients experienced anatomic success with surgery, but not in BCVA. Early surgery might be considered for eyes at FS prior to the occurrence of LMH or FRD. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:574-582.].

Combination of optical coherence tomography (OCT) and OCT angiography increases diagnostic efficacy of Parkinson's disease.

BACKGROUND: To assess the diagnostic efficacy of optical coherence tomography (OCT) and OCT angiography (OCTA) in Parkinson's disease (PD). METHODS: OCT was used to obtain macular parameters and peripapillary retinal nerve fiber layer (RNFL) thickness. The macular superficial retinal vessel and foveal avascular zone (FAZ) were quantified with OCTA. The area under the receiver operating characteristic curve (AUC) indicated the diagnostic efficacy of the parameters. RESULTS: Thirty-five eyes from 35 PD patients and 35 eyes from 35 age-matched healthy subjects who served as controls were evaluated. The mean RNFL thickness overall and the thicknesses of the other three quadrants were similar in PD patients compared with controls (P≥0.358). The RNFL thickness at the temporal quadrant, total macular volume (TMV), macular retinal thickness (MRT), and ganglion cell-inner plexiform layer complex (GCL-IPL) thickness were reduced in the eyes of PD patients (P≤0.046). There was no difference between the CMT of PD patients compared with control subjects (P=0.163). The vessel length density (VLD) in the central, inner and full regions; vessel perfusion density (VPD) in all regions; and the FAZ circularity index in PD patients were significantly lower than in controls (P≤0.049). The AUC of the VLD in PD in the central, inner and full regions were 0.712, 0.728, and 0.650, respectively; The VPD in the central, inner and full region were 0.711, 0.756, and 0.682, respectively. The mean RNFL thickness in the temporal quadrant, TMV and MRT revealed an AUC of 0.718, 0.693 and 0.699, respectively. The VPD in the outer region, FAZ circularity and GCL-IPL thickness did not have diagnostic ability in distinguishing PD from normal eyes (P≥0.05). The AUCs of a combination of the VLD in the inner region and TMV, the VLD in the inner region and MRT, the VPD in the inner region and TMV, and the VPD in the inner region and MRT, were 0.843, 0.849, 0.849, and 0.848, respectively (P≤0.001). CONCLUSIONS: Decreased OCT and OCTA parameters were detected in the eyes of PD patients. Combined non-invasive measurements of OCT and OCTA had better diagnostic ability than either alone, and may provide an additional biomarker for PD progression.

Association between individual retinal layer thickness and visual acuity in patients with epiretinal membrane: a pilot study.

PURPOSE: We investigated the correlation between visual acuity (VA) and individual retinal layer thickness in the foveal, parafoveal, and perifoveal regions of patients with an idiopathic epiretinal membrane (ERM). METHODS: One hundred and five subjects presenting with unilateral idiopathic ERM were included in this study. We segmented each patient's optical coherence tomography (OCT) image into seven layers and calculated the mean layer thickness in the foveal, parafoveal, and perifoveal regions using the Iowa Reference Algorithm. In 105 patients with ERM, we detected correlations between their macular regions' individual retinal layer thickness and their best corrected VA. Thirty-one of the 105 patients with ERM underwent vitrectomy and completed six months of follow-up. We then compared the 31 surgical patients' preoperative and postoperative individual retinal layer thickness in each macular region. Additionally, the association between preoperative individual retinal layer thickness in each macular region and VA six months post-surgery in patients with ≥ two Snellen lines of visual improvement was determined. RESULTS: Multiple linear regression analysis showed that the inner nuclear layer (INL) thickness in the foveal, parafoveal, and perifoveal region were all associated with VA in the 105 patients (R 2 = 0.344, P < 0.001; R 2 = 0.427, P < 0.001; and R 2 = 0.340, P < 0.001, respectively). Thirty-one surgical patients 6 months post-surgery showed significantly decreased thicknesses (P ≤ 0.012) of the foveal INL, inner plexiform layer (IPL), and outer nuclear layer (ONL); the parafoveal retina nerve fiber layer (RNFL), IPL, INL, and ONL; and the perifoveal RNFL, IPL, INL, ganglion cell layer (GCL), outer plexiform layer (OPL), and photoreceptor layer (PRL). We found a weak correlation between postoperative VA and preoperative foveal and perifoveal RNFL thickness (r = 0.404 and r = 0.359, respectively), and a moderate correlation between postoperative VA and preoperative foveal and parafoveal INL thickness (r = 0.529 and r = 0.583, respectively) in the 31 surgical patients (P ≤ 0.047). The preoperative INL thickness in the foveal, parafoveal, and perifoveal regions showed a moderate to strong correlation (r = 0.507, 0.644, and 0.548, respectively), with postoperative VA in patients with ≥ 2 lines of visual improvement (P ≤ 0.038). CONCLUSION: We detected a correlation between retinal damage and VA in the parafoveal, perifoveal, and foveal regions. Our results suggest that INL thickness in all macular regions may be a prognostic factor for postoperative VA in ERM patients.

Effect of pyridone agent on blood-retinal barrier in diabetic mice.

AIM: To evaluate the therapeutic effect of fluorofenidone on disrupted blood-retinal barrier in the diabetic mice and uncover its underlying mechanism. METHODS: db/db mice were randomly chosen for treatment with daily doses of fluorofenidone or placebo at 5-week-old, treatment continued until mice reach 24-week-old. Then, expression of transcriptiona factor insulin gene enhancer binding protein-1 (Islet-1) and vascular endothelial growth factor (VEGF) in murine retinas were evaluated. Retinal vascular permeability was assessed by examining the level of albumin in db/db murine retinas. Furthermore, the retinal vessel tight junction was estimated by checking the level of occludin in the murine retinal tissues. RESULTS: After occurrence of diabetic retinopthy in db/db mice, expressions of transcritpional factor Islet-1 was found to be upregulated in db/db murine retinas compared with non-diabetic controls. Similar to expression pattern of Islet-1, VEGF were also demonstrated to be increased in retinas of db/db mice, which was accompanied by increased retinal vascular leakage and decreased tight junction protein level. Systemetic administration of fluorofenidone repaired broken retinal vascular tight junction by restoring occludin expression in db/db retinal tissue. Consequently, retinal vascular premeability were indicated to be reduced by examining the transudative albumin level in diabetic retinal tissues. Both Islet-1 and VEGF expression were inhibited in the retinas of db/db mice after treatment with fluorofenidone. CONCLUSION: Fluorofenidone significantly protectes retinal tight junction and reduces retinal vascular leakage. The phenomenon can be partially attributed to reducing overexpression of Islet-1 and VEGF in diabetic retinal tissues.