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Objectives. To characterize the microstructural alterations of peripapillary choriocapillaris in young adult high myopes using optical coherence tomography angiography (OCTA) and to explore factors involved in the alterations. Methods. This cross-sectional control study included 205 eyes (95 with high myopia and 110 with mild-moderate myopia). The choroidal vascular network was imaged using OCTA, and the images underwent manual adjustments to determine the peripapillary atrophy (PPA)-β zone and microvascular dropout (MvD). The area of MvD and PPA-β zone, spherical equivalent (SE), and axial length (AL) were collected and compared across groups. Results. The MvD was identified in 195 eyes (95.1%). Highly myopic eyes exhibited significantly greater area of PPA-β zone (1.221 ± 0.073 vs. 0.562 ± 0.383 mm2, P = 0.001) and MvD (0.248 ± 0.191 vs. 0.089 ± 0.082 mm2, P P

AIM: To evaluate the effectiveness of rectangular 3-snip punctoplasty versus punch punctoplasty via Kelly punch with silicone intubation for the management of acquired external punctal stenosis (AEPS). METHODS: A prospective, randomized, comparative study was performed on 123 eyes of 94 patients with AEPS. Patients were recruited into either group of rectangular 3-snip punctoplasty (group A) or group of punch punctoplasty with silicone intubation (group B). Outcomes measured were Munk score, grade of punctal stenosis, fluorescein dye disappearance time test (FDDT) and tear meniscus height (TMH) 6 and 12mo after surgery. RESULTS: Twelve months after surgery, Munk score, FDDT and TMH significantly decreased in both groups compared with the baseline (all P

Fundus fluorescein angiography (FFA) is widely used in clinical ophthalmic diagnosis and treatment with the requirement of adverse fluorescent dyes injection. Recently, many deep Convolutional Neural Network(CNN)-based methods have been proposed to estimate FFA from color fundus (CF) images to eliminate the use of adverse fluorescent dyes. However, the robustness of these methods is affected by pathological changes.In this work, we present a CNN-based approach, lesion-aware generative adversarial networks (LA-GAN), to enhance the visual effect of lesion characteristics in the generated FFA images. First, we lead the generator notice lesion information by joint learning with lesion region segmentation. A new hierarchical correlation multi-task framework for high-resolution images is designed. Second, to enhance the visual contrast between normal regions and lesion regions, a newly designed region-level adversarial loss is used rather than the image-level adversarial loss. The code is publicly available at: https://github.com/nicetomeetu21/LA-GAN.The effectiveness of LA-Net has been verified in data with branch retinal vein occlusion. The proposed model reported as measures of generation performance a mean structural similarity (SSIM) of 0.536, mean learned perceptual image patch similarity (LPIPS) 0.312, outperforming other FFA generation and general image generation methods. Further, due to the proposed multi-task learning framework, the lesion-region segmentation performance was further reported as the mean Dice increased from 0.714 to 0.797 and the mean accuracy increased from 0.873 to 0.905, outperforming general single-task image segmentation methods.The results show that the visual effect of lesion characteristics can be improved by employing the region-level adversarial loss and the hierarchical correlation multi-task framework respectively. Based on the results of comparison with the state-of-the-art methods, LA-GAN is not only effective for CF-to-FFA translation, but also effective for lesion-region segmentation. Thus, it may be used for various image translation and lesion segmentation tasks in future research.

Objectives To optimize parameters of contact lenses (CLs) and evaluate their ability to protect the cornea during vitreoretinal surgery. Methods We compared the protective effects of balanced saline solution, viscoelastic agent, and CLs on rabbit corneas under conditions simulating vitreoretinal surgery. We evaluated CLs of different thicknesses and compared the protective effects of polymethyl methacrylate (PMMA) and gas-permeable fluorosilicone acrylate (XO) lenses on the corneas of rabbits and patients with severe proliferative diabetic retinopathy (PDR). The corneal fluorescein staining score (FSS) was measured to compare the protective effects of CLs. Results The FSS was significantly lower in the PMMA group than in the balanced saline solution and viscoelastic agent groups. The thickness of the PMMA lenses had no significant effect on the FSS. The FSS was significantly higher in the PMMA group than in the XO group. In patients with PDR, on day 1 after vitreoretinal surgery, the FSS was significantly higher in the PMMA group than in the XO group, although no significant difference was observed on postoperative day 7. Conclusion The XO lens offers better corneal protection during noncontact wide-angle vitreoretinal surgery and protects the corneal epithelium more efficiently during vitrectomy in patients with PDR, irrespective of its thickness.

PURPOSE To compare the efficacy of a modified perfluorocarbon liquid-assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes. METHODS This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid-assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery. RESULTS Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044). CONCLUSION The perfluorocarbon liquid-assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.

Vitreous fibrovascular membranes (FVMs), the hallmark of proliferative diabetic retinopathy (PDR), cause retinal hemorrhage, detachment and eventually blindness. However, little is known about the pathophysiology of FVM. In this study, we employed single-cell RNA sequencing on surgically harvested PDR-FVMs and generated a comprehensive cell atlas of FVM. A total of 8 cellular compositions were identified, with microglia as the major cell population. We identified a GPNMB+ subpopulation of microglia, which presented both profibrotic and fibrogenic properties. Pseudotime analysis further revealed the profibrotic microglia was uniquely differentiated from retina-resident microglia and expanded in PDR setting. Ligand-receptor interactions between the profibrotic microglia and cytokines upregulated in PDR vitreous implicated the involvement of several pathways, including CCR5, IFNGR1 and CD44 signaling, in the microglial activation within PDR microenvironment. Collectively, our description of the novel microglia phenotypes in PDR-FVM may offer new insight into the cellular and molecular mechanism underlying the pathogenesis of DR, as well as potential signaling pathways amenable to disease-specific intervention.

PurposeTo investigate the influence of preoperative adjunctive anti-VEGF drug (Conbercept) on vitreous inflammatory cytokines and chemokines profiles and whether those cytokines were associated with early macular edema (ME) after surgery for patients with proliferative diabetic retinopathy (PDR).MethodsIn this post hoc analysis of the CONCEPT clinical trial, subjects with PDR underwent vitrectomy were included and vitreous samples were collected at the start of vitrectomy. Levels of vitreous VEGF, 17 inflammatory cytokines, and 11 chemokines were measured using Luminex multiplex technology. Subjects were then divided into groups based on with (Pre-IV) or without (No-Pre-IV) preoperative intravitreous injection of Conbercept; with or without early ME after surgery.ResultsThere was no difference between Pre-IV (13/30) and No-Pre-IV (7/29) concerning the ratio of patients with early ME (p = 0.17). After preoperative intravitreous injection of Conbercept, VEGF level dramatically decreased (p = 0.001), TNF-α (p = 0.002), and IP-10 (p = 0.018) increased in Pre-IV group. In patients with early ME after surgery, however, a number of cytokines increased, including IL-1β (p = 0.008), IL-2 (p = 0.023), IL-4 (p = 0.030), IL-9 (p = 0.02), IL-10 (p = 0.002), IL-12 (p = 0.001), IL-13 (p = 0.031), IL-17A (p = 0.008), TNF-α (p = 0.012), CXCL9 (p = 0.023), G-CSF (p = 0.019), MCP-1 (p = 0.048), and RANTES (p = 0.016).ConclusionWe found the preoperative adjunctive Conbercept injection has limited influence on the levels of vitreous inflammatory cytokines and chemokines in PDR. The elevated levels of a series of cytokines might be associated with early inflammation after vitrectomy, which may lead to postoperative ME.

BackgroundProliferative diabetic retinopathy (PDR), as one of the main microvascular complications of diabetes mellitus, seriously threatens the visual function of the working-age population; yet, the underlying pathogenesis is still poorly understood. This study aimed to identify the distinct exosomal circular RNA (circRNA) expression in PDR serum and preliminarily explore the potential pro-angiogenic mechanism of specific exosomal circRNAs.MethodsWe collected serum samples from 10 patients with PDR and 10 patients with age-matched senile cataract to detect the exosomal differentially expressed genes (DEGs) of circRNAs via high-throughput sequencing, followed by validation with quantitative real-time PCR (qRT-PCR). Next, bioinformatics analyses including competitive endogenous RNA (ceRNA) network, protein–protein interaction network (PPI), and functional enrichment analyses were performed. In addition, the potential function of circFndc3b (hsa_circ_0006156) derived from high-glucose-induced endothelial cells was analyzed in human retinal vascular endothelial cells (HRVECs).ResultsIn total, 26 circRNAs, 106 microRNAs (miRNAs), and 2,264 messenger RNAs (mRNAs) were identified as differentially expressed in PDR serum exosomes compared with cataract serum exosomes (fold change > 1, P < 0.05). A circRNA–miRNA–mRNA ceRNA network was established. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the mRNAs were mainly enriched in the PI3K–Akt signaling pathway, MAPK signaling pathway, Wnt signaling pathway, and VEGF signaling pathway. The PPI network and module analysis identified 10 hub genes, including RhoA, Cdc42, and RASA1. Finally, circFndc3b and exosomes derived from high-glucose-induced endothelial cells were identified with the capability to facilitate angiogenesis in vitro.ConclusionAberrant profiling of exosomal circRNAs in PDR serum was identified. CircFndc3b derived from high-glucose-induced endothelial cells may play an important role in the angiogenesis of PDR.

Aim To introduce a new method for suprachoroidal fluid drainage before 23-gauge pars plana vitrectomy. Methods A 15° side-port blade was firstly used to create a sclerotomy into the suprachoroidal space for initial drainage. A 30-guage needle was then applied to inject balanced saline solution through the existing sclerotomy for further drainage. After most of the suprachoroidal fluid was drained, standard 3-port 23-guage pars plana vitrectomy was performed. Results We have succeeded in using this technique to treat five patients with retinal detachment and kissing choroidal detachment (KCD). The choroidal detachment was visibly recessed in all cases after drainage with no intraoperative complications. After removal of silicon oil at 3mo follow-up, all patients obtained a reattached retina. No postoperative complications such as hypotony and endophthalmitis occurred. Conclusion The new technique is efficient and safe for suprachoroidal fluid drainage for patients with rhegmatogenous retinal detachment. In future, further larger series are needed to attest to its safety and efficacy.

Objective: To investigate the potential correlation between complement factor B polymorphisms and age-related macular degeneration. Methods: We retrieved relevant articles systematically by searching PubMed and Web of Science databases. The pooled odds ratios and 95% confidence intervals were calculated for five complement factor B polymorphism rs641153, rs4151667, rs1048709, rs2072633, and rs12614 using data from included articles in both random effects and fixed effect models. Subgroup meta-analysis based on age-related macular degeneration type, choroidal neovascular disease (rs641153 and rs4151667), geographic atrophy (rs641153 and rs4151667), and races was also performed. Results: In the overall comparison, we observed that the distribution of rs641153 and the risk of age-related macular degeneration were significantly correlated (p Conclusion: Collectively, we demonstrated that the complement factor B genes rs641153 and rs4151667, but not rs1048709, rs2072633, rs12614, were associated with the susceptibility of age-related macular degeneration and might play predictive roles in future age-related macular degeneration diagnosis. More studies are needed to verify these findings.

NLRP3, as a crucial inflammasome component, plays important roles in age-related macular degeneration. Though some activators of NLRP3 have been studied, microRNAs (miRNAs) which potentially regulate NLRP3 messenger RNA (mRNA) have not been fully explored in retinal pigment epithelial (RPE) cells and retinopathy. In this study, by miRNA microarray profiling and bioinformatic analysis, we identified that four miRNAs, miR-4286, miR-223-3p, miR-365a, miR-22-3p, may target NLRP3 mRNA in RPE inflammatory damage in vivo. Further, real-time polymerase chain reaction verified that only miR-22-3p was significantly decreased, which was associated with NLRP3 upregulation in blue-light-induced retinopathy. Mechanistically, the dual-fluorescent reporter suggested miR-22-3p directly binds NLRP3 mRNA. Moreover, overexpression of miR-22-3p could significantly reduce whereas inhibition miR-22-3p could increase the mRNA and protein expressions of NLRP3, Caspase-1, and mature IL-1β. Collectively, our results indicate that miR-22-3p plays a suppressive role in RPE damage by targeting NLRP3, which provides new insights into the future intervention to retinopathy.

An acoustic coupling scheme largely determines the performance of optical-resolution photoacoustic microscopy (OR-PAM), including practicability, sensitivity, and stability. In this study, we propose OR-PAM based on a local–flexible acoustic coupling scheme, which includes a well-designed combiner connecting a set of circulating systems. The combiner integrates an objective lens and an ultrasonic transducer, controls the water level, restricts the flow rate, and drains bubbles. The circulating system provides sustained and steady flowing water. The flowing water constrained in the combiner and the circulating system forms a flexible and stable local contact between the sample and the transducer. Phantom experiments demonstrate that the proposed method can maintain high optical resolution but improve the detection sensitivity by approximately 1.9 times in comparison to dry coupling. In vivo imaging experiments of the mouse eyeground are conducted to examine the practicability of the proposed system in biomedicine. Moreover, in vivo experiments show that OR-PAM based on local–flexible coupling can reveal more details of eyeground microvasculatures, benefiting from its enhanced sensitivity. These merits promise that OR-PAM based on local–flexible coupling may have broad applications in biomedical fields.

Photoacoustic microscopy (PAM) is an emerging biomedical imaging modality, combining good acoustic resolution in deep tissue and rich functional biomedical information. Spatial resolution and spatial isotropy are two of the most important indexes of a PAM. In this study, we propose a PAM scheme based on an aspheric acoustic mirror group to achieve the subwavelength resolution and enhance the spatial isotropy. The mirror group consists of an ellipsoid acoustic mirror and a parabolic acoustic mirror. The ellipsoid acoustic mirror expands the cone angle of signal collection, and the parabolic acoustic mirror reduces the cone angle of the PA beam. Their combination equivalently expands the numerical aperture of acoustic detection. Phantom experiments demonstrate that the proposed scheme can achieve the subwavelength resolution. Simultaneously, its spatial isotropy is improved from 48.2% to 96.7%. An in vivo mouse brain imaging experiment examines the biomedical practicability of the method. This method may be found wide potential applications in biomedicine.

Optical-resolution photoacoustic microscopy (OR-PAM) is a promising noninvasive biomedical imaging technology with label-free optical absorption contrasts. Performance of OR-PAM is usually closely related to the optical-acoustic combiner. In this study, we propose an optical-acoustic combiner based on a flat acoustic reflector and an off-axis parabolic acoustic mirror with a conical bore. Quantitative simulation and experiments demonstrated that this combiner can provide better acoustic focusing performance and detection sensitivity. Moreover, OR-PAM is based on the combiner suffer low optical disorders, which guarantees the good resolution. In vivo experiments of the mouse brain and the iris were also conducted to show the practicability of the combiner in biomedicine. This proposed optical-acoustic combiner realizes a high-quality optical-acoustic confocal alignment with minimal optical disorders and acoustic insertion loss, strong acoustic focusing, and easy implementation. These characteristics might be useful for improving the performance of OR-PAM.

Objectives. Idiopathic epiretinal membrane (iERM) or idiopathic macular hole (iMH) is frequently used as a “healthy” control in comparison of vitreous cytokines with other vitreoretinal diseases. This study aimed to investigate if there is a difference in vitreal cytokines expression between patients with iERM and iMH. Methods. In this prospective study, all subjects received standard pars plana vitrectomy surgery, and 0.5 ml of native vitreous sample was extracted during the vitrectomy. Luminex technology and enzyme-linked immunosorbent assay were used to profile the concentration of 52 classic angiogenic, inflammatory, and profibrotic cytokines and chemokines. Statistical analyses were performed by the Mann–Whitney U test, followed by multiple comparisons by the Bonferroni correction. Results. Vitreal samples from 13 iERM and 24 iMH were studied. Of the 52 tested cytokines, 41 were similar in expression, and 5 were under the detection limit, while 6 cytokines (MMP-8, Eotaxin, MIP-1a, RANTES, TGF-β2, and IL-4) were differently expressed between two groups ( p < 0.05 ). Nevertheless, these significances disappeared after the adjustment of Bonferroni correction. Conclusion. The tested cytokines showed similar expression between iERM and iMH patients. This indicates that eyes with iERM or iMH can be together served as “healthy” controls.

Retinal diseases, the leading causes of vison loss and blindness, are associated with complicated pathogeneses such as angiogenesis, inflammation, immune regulation, fibrous proliferation, and neurodegeneration. The retina is a complex tissue, where the various resident cell types communicate between themselves and with cells from the blood and immune systems. Exosomes, which are bilayer membrane vesicles with diameters of 30–150 nm, carry a variety of proteins, lipids, and nucleic acids, and participate in cell-to-cell communication. Recently, the roles of exosomes in pathophysiological process and their therapeutic potential have been emerging. Here, we critically review the roles of exosomes as possible intracellular mediators and discuss the possibility of using exosomes as therapeutic agents in retinal diseases.

We described a 65-year-old male with choroidal metastases (CM) from non-small cell lung cancer (NSCLC). Pembrolizumab (Keytruda) combined with pemetrexed and capecitabine achieved excellent outcomes. After two cycles of pembrolizumab and chemotherapy, blurred vision and left eye pain were significantly relieved. Imaging and ophthalmologic examinations demonstrated complete resolution of the CM, as well as reduction of pulmonary shadow. CM from NSCLC shows complete and durable response to pembrolizumab and chemotherapy. We suggesting that immunotherapy combined with chemotherapy is a promising treatment for CM from NSCLC.

Background Quantification of neovascularization changes in terms of neovascular complex (NVC) acquired from the optical coherence tomography angiography (OCTA) imaging is extremely important for diagnosis and treatment monitoring of proliferative diabetic retinopathy (PDR). However, only few vessel extraction methods have so far been reported to quantify neovascular changes in NVC with proliferative diabetic retinopathy PDR based on OCTA images. Methods Here we propose an optimized approach to segment blood vessels, which is based on an improved vascular connectivity analysis (VCA) algorithm and combined with morphological characterization and elimination of noise and artifacts. The length and width of vessels are obtained in the quantitative assessment of microvascular network. The feasibility of the proposed method is further studied by a treatment monitoring and statistical analysis process, as we have monitored and statistically analyzed the changes of NVC based on sampled OCTA images of PDR patients (N = 14) after treatment by intravitreal injection of conbercept. Results The proposed method has demonstrated better performance in accuracy compared with existing algorithms and can thus be used for PRD treatment monitoring. Following the PDR treatment monitoring study, our data has shown that from the 1st day to 7th day of treatment, the averaged (arithmetic mean) length of NVC has been substantially shortened by 36.8% (P P Conclusion The results and analysis have confirmed that the proposed optimization process by the improved VCA method is both effective and feasible to segment and quantify the NVC with lower noise and fewer artifacts. Thus, it can be potentially applied to monitor the fibrovascular regression during the treatment period. Clinical Trial Registration This trial is registered with the Chinese Clinical Trial Registry (Registered 27 December 2017, http://www.chictr.org.cn, registration number ChiCTR-IPR-17014160).

AIM: To explore retinal displacement after surgical treatment for idiopathic macular hole (IMH) with different internal limiting membrane (ILM) peeling patterns. METHODS: Totally 22 eyes from 20 patients with IMH were randomly allocated into two groups, N-T group (11 eyes) and T-N group (11 eyes). For patients in N-T group, ILM was peeled off from nasal to temporal retina. For patients in T-N group, ILM was peeled off from temporal to nasal retina. Preoperative, postoperative 1, 3, and 6mo, autofluorescence fundus images were collected for manual measurement of distances of fixed nasal (N), temporal (T), superior (S), and inferior (I) retinal points (bifurcation or crossing of retinal vessels) around the macula to the optic disc (OD). These were respectively defined as N-OD, T-OD, S-OD, and I-OD. The retinal displacement, macular hole closure rate, and best corrected visual acuity (BCVA) were compared between the two groups after surgery. RESULTS: At postoperative 1, 3, and 6mo, the macula slipped toward the OD, manifested by the decreased T-OD, N-OD, S-OD, and I-OD (P

Photoacoustic imaging is a potential candidate for in vivo brain imaging, whereas, its imaging performance could be degraded by inhomogeneous multi-layered media, consisted of scalp and skull. In this work, we propose a low-artifact photoacoustic microscopy (LAPAM) scheme, which combines conventional acoustic-resolution photoacoustic microscopy with scanning acoustic microscopy to suppress the reflection artifacts induced by multi-layers. Based on similar propagation characteristics of photoacoustic signals and ultrasonic echoes, the ultrasonic echoes can be employed as the filters to suppress the reflection artifacts to obtain low-artifact photoacoustic images. Phantom experiment is used to validate the effectiveness of this method. Furthermore, LAPAM is applied for in-vivo imaging mouse brain without removing the scalp and the skull. Experimental results show that the proposed method successfully achieves the low-artifact brain image, which demonstrates the practical applicability of LAPAM. This work might improve the photoacoustic imaging quality in many biomedical applications which involve tissues with complex acoustic properties, such as brain imaging through scalp and skull.

Objective To compare the efficacy of ranibizumab plus fufang xueshuantong capsule (cFXST) with the efficacy of ranibizumab alone in treatment of exudative age-related macular degeneration. Methods This prospective, randomized, controlled, pilot study included 38 eyes from 38 patients with exudative age-related macular degeneration (AMD) that were randomly allocated into two cohorts of 19 eyes each: ranibizumab (Cr) and ranibizumab plus cFXST (Cfr). All patients received three monthly injections of ranibizumab. Patients in Cfr also received daily oral supplementation of cFXST. Best corrected visual acuity (BCVA) and thickness of the choroidal neovascularization-pigment epithelial detachment (CNV-PED) complex (measured by optical coherence tomography) were recorded at baseline and at 1 and 3 months after the first intravitreal injection of ranibizumab. Results In the Cfr, the CNV-PED complex thickness was reduced by 31.7% and 36.1% at 1 and 3 months, respectively; these reductions were significantly greater than the 19.7% and 24.2% reductions in the Cr. BCVA improvement was significantly greater in the Cfr than in the Cr after 3 months; the proportion of patients with functional response was also greater in the Cfr than in the Cr (16/16 vs. 8/17). Conclusion Oral cFXST increases the efficacy of short-term ranibizumab treatment for exudative AMD.

Background: Quantification of neovascularization changes in fibrovascular membrane (FVM) acquired from optical coherence tomography angiography (OCTA) imaging is extremely important for diagnosis and treatment monitoring of proliferative diabetic retinopathy (PDR). However, few vessel extraction methods have been reported for quantifying the neovascular changes on fibrovascular membrane (FVM) in proliferative diabetic retinopathy PDR based on OCTA imaging.Methods: We propose an optimized approach to segment blood vessels based on an improved vascular connectivity analysis (VCA) algorithm with a combined effort of morphological characterization as well as noise and artifacts elimination. The length and width of vessels are also obtained in quantitative assessment of the microvascular network. Furthermore, we also study the feasibility of the proposed method by monitoring changes of neovascularization on FVM, which is based on the OCTA images of PDR patients after treatment by intravitreal injection of conbercept (IVC).Results: The proposed method has achieved better performance compared with existing algorithms on accuracy and can be used for PRD treatment monitoring. In the study of PDR treatment monitoring, the data show that from the beginning (0 day) to 5th day of treatment, the total length of neovascularization on FVM in this area has been significantly shortened by an 77.8% reduction, indicating significant effects from the treatment applied. Besides, the average width of the neovascularization on FVM at the 7th day after treatment has been increased by 158%, which indicates that most of the narrow neovascularization has been reduced. Conclusion: The result and analysis have confirmed that the proposed optimization process with improved VCA method is both effective and feasible to segment and quantify the neovascularization on FVM with less noise and artifacts, thus can be readily applied to monitor the fibrovascular regression within the treatment period.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (Registered 27 December 2017, http://www.chictr.org.cn, registration number 17014160).

Background Internal limiting membrane (ILM) peeling increases the idiopathic macular hole (IMH) closure rate but causes the inner retina dimplings. This study is to introduce a method to minimally peel the ILM, and with the ILM flap to ensure the IMH closure. Methods Twelve consecutive IMH eyes were treated with the minimal ILM peeling with ILM flap technique. The ILM around the MH is peeled off in an annular shape with a width of approximately 200 to 300 μm. A tongue-shape ILM flap is created in the superior retina and the inferior margin of ILM is not peeled off. The ILM flap is then inverted to cover the MH, followed by fluid-air exchange and air or silicon tamponade. Spectral domain-optical coherence tomography (SD-OCT) and en face OCT for morphological assessment, best corrected visual acuity (BCVA) and multifocal electroretinogram (ERG) for functional evaluation were performed at baseline and at each postoperative follow-up. Results All the 12 eyes achieved macular hole closure on SD-OCT after surgery (100%). At baseline, the mean preoperative BCVA was 0.83 ± 0.33 and it improved to 0.39 ± 0.28 postoperatively (p En face OCT showed the inner retinal dimplings were localized only in superior ILM-free retinas (7 eyes). The mERG response density in the central (R1), para-central (R2), R1/R2 ring ratios were remarkably improved at the last follow-up (p = 0.001, p = 0.033, p = 0.018, respectively). Conclusions The minimal ILM peeling with ILM flap technique can achieve favorable MH closure with less inner retinal dimplings and has promising visual recovery for IMH eyes.

The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover, post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.

The aim of this review is to determine whether vitreomacular adhesion (VMA) or vitreomacular traction (VMT) has an influence on the outcomes of antivascular endothelium growth factor (anti-VEGF) treatment neovascular age-related macular degeneration (nAMD).A systematic literature search was performed in Pubmed.gov, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed and ClinicalTrials.gov up to 30 June 2016 to identify eligible studies.Nine studies and 2212 participants were finally identified. At month 6, the mean improvement in best-corrected visual acuity (BCVA) and mean decline in central retinal thickness (CRT) of the VMA/VMT(+) group was less than that of the VMA/VMT(-) group (95% CI -3.05 to -0.96 letters, p=0.0002; 15.53 to 32.98 μm, p0.00001; respectively); at month 12, there was a small or only marginally significant difference (-0.01 to 2.00 letters, p=0.05; 0.17 to 23.7 μm, p=0.05; respectively) between the groups. During the 12 months, however, the VMA/VMT(+) group required more injections ((0.25 to 0.95), p=0.0008).In using anti-VEGF drugs to treat nAMD, clinicians should take into account the fact that concurrent VMA or VMT might antagonise the efficacy of anti-VEGF drugs during the early stage of treatment.

Letter to the editor

To quantify the preoperative neovascular change pattern on the fibrovascular membrane (FVM) within 7 days after intravitreal injection of conbercept (IVC) using optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR). Prospective, observational study of PDR patients with visible FVM receiving or not receiving IVC. Neovascular changes were assessed by OCTA pre-IVC and 1, 3, 5, and 7 days post-IVC. Vessel skeleton density (SD) and vessel density (VD) were quantified by an intensity-based optical microangiography algorithm. The interclass correlation coefficient (ICC) was calculated to assess the agreement between measurements. The SD and VD were compared between follow-ups using repeated-measures analysis in the IVC group. The ICC was 0.992 (95% confidence interval [CI]: 0.982–0.996) for SD and 0.926 (95% CI: 0.838–0.912) for VD of neovascularization. The neovascularization on FVM significantly regressed in the IVC group (n = 16) compared with no IVC (n = 8) (p = 0.001 for SD and p