Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Objective To explore the efficacy and safety of pars plan vitrectomy(PPV)combined with internal limit-ing membrane(ILM)covering surgery in patients with large-diameter idiopathic macular holes(IMH)using optical coher-ence tomography angiography(OCTA)and microperimetry.Methods Twenty-three eyes of 23 patients with large-diame-ter IMH treated at the Eye Hospital Affiliated with Nanchang University from February 2023 to July 2023 were selected.The patients'best-corrected visual acuity(BCVA),hole closure rate,microcirculation[perfusion density at the superficial cap-illary plexus(PSCP)and vascular density at the retinal superficial capillary plexus(VSCP)]in the macular area(divided into central,inner and outer regions),macular sensitivity(MS),fixation stability,and foveal avascular zone(FAZ)area were observed before surgery and at 1 week,1 month,3 months,and 6 months after surgery.Changes in eye parameters before and after surgery were compared,and the correlation between parameters was analyzed.Results After a 6-month follow-up,all macular holes in the affected eyes were closed,with a closure rate of 100％.Compared to before surgery,the BCVA of the patients improved gradually at 1 week,1 month,3 months,and 6 months after surgery,and the differ-ences between any two time points were statistically significant(all P＜0.05).The FAZ area decreased at 1 week,1 month,3 months,and 6 months after surgery compared to before surgery,and the differences were statistically significant(all P＜0.05).The VSCP in the three regions showed a decrease at 1 week postoperatively and an increase at 6 months postoperatively compared to before surgery,and the differences were statistically significant(both P＜0.05).The PSCP in-creased at 3 months and 6 months postoperatively compared to before surgery,with statistically significant differences(both P＜0.05).The 12° MS increased at 1 month,3 months,and 6 months after surgery compared to before surgery,with statistically significant differences(all P＜0.05).The proportions of fixation points within 2° and 4° increased at 1 month,3 months,and 6 months postoperatively compared to before surgery,with statistically significant differences(all P＜0.05).The proportion of fixation points within 4° increased at 1 week postoperatively compared to before surgery,with a statistically significant difference(P＜0.05).Correlation analysis showed that preoperative MS and the proportion of fixa-tion points within 2° were negatively correlated with BCVA(logMAR)at 6 months postoperatively(r=-0.819,-0.790,both P＜0.05),while preoperative FAZ area and minimum hole diameter were positively correlated with BCVA(logMAR)at 6 months postoperatively(r=0.596,0.853,both P＜0.05).The preoperative VSCP in the inner and outer regions were negatively correlated with BCVA(logMAR)at 6 months postoperatively(r=-0.521,-0.570,both P＜0.05).Conclu-sion The results of OCTA and microperimetry show that after treatment with PPV and ILM covering surgery,the closure rate of large-diameter IMH is good,and all indicators have improved compared to before surgery.

Diabetic macular edema(DME)is the most common complication of diabetic retinopathy,which can cause vision loss in patients.The nosogenesis of DME is complicated,and about 1/3 DME patients have poor response to anti-vascular endothelial growth factor therapy,which is defined as refractory DME.The early identification of the risk factors of refractory DME is crucial and helpful for doctors to predict the prognosis of DME and guide clinical treatment.This arti-cle reviews the risk factors of refractory DME.

Objective To explore the efficacy and safety of subretinal injection of conbercept in treating refractory neovascular age-related macular degeneration(nAMD).Methods In this prospective clinical study,17 eyes of 17 pa-tients diagnosed with refractory nAMD at the Department of Fundus Disease,the Affiliated Eye Hospital of Nanchang Uni-versity from March 2022 to September 2023 were enrolled.The 10 g·L-1 conbercept was injected into the subretinal area of the macular area using a 41G ultra-fine microneedle.If retinal exudation was found in the macular area by optical coherence tomography during the follow-up,the intravitreal injection of 10 g·L-1 conbercept was performed.The best corrected vis-ual acuity(BCVA),central macular retinal thickness(CMT),number of injections and complications were recorded before and 1,3,6,and 12 months after the operation.Results Compared with the preoperative values,the BCVA of patients significantly improved(all P＜0.001)1,3,6 and 12 months postoperatively.There was no significant change in BCVA at each time point after operation(all P＞0.05).Compared with pre-operation,CMT of patients significantly decreased at 1,3,6 and 12 months after operation(all P＜0.001).From 1 month to 12 months after the operation,the CMT of patients gradually decreased(all P＜0.001).Pearson correlation analysis showed that there were positive correlations between pre-operative BCVA and preoperative CMT,preoperative BCVA and 12-month postoperative BCVA(r=0.643,P=0.005;r=0.634,P=0.006).During the treatment,the number of anti-vascular endothelial growth factor injections in 17 eyes was(1.35±0.61)times,with 1 time in 12 eyes,2 times in 4 eyes,and 3 times in 1 eye.Correlation analysis showed that the number of injections was positively correlated with preoperative CMT(r=0.664,P=0.004).No intraoperative or postop-erative complications related to the operation occurred in 17 eyes.Conclusion Subretinal injection of conbercept,which can reduce CMT and improve visual prognosis,is a safe and effective treatment method for refractory nAMD.

AIM:To investigate the mechanism by which N6-methyladenosine(m6A)methylase methyltrans-ferase-like protein 3(METTL3)regulates the differentiation of human bone marrow mesenchymal stem cells(MSCs)into adipocytes in vitro.METHODS:Lentiviral vectors of METTL3,AKT serine/threonine kinase 1(AKT1),peroxisome pro-liferator-activated receptor γ(PPARγ)and YTH m6A RNA binding protein F2(YTHDF2)were constructed to package lentiviral particles and used to infect MSCs.A human bone MSC adipogenic differentiation kit was used to induce the MSCs into adipocytes.Additionally,the adipocytes were stained by oil red O.The recombinant vector of METTL3 mutant was constructed using molecular cloning to confirm the regulatory effect of the key site of m6A in METTL3 on the target genes.Actinomycin D was applied to MSCs with overexpression of YTHDF2 to evaluate the effect of YTHDF2 recognition on the mRNA and protein expression of AKT1.The RNA pull-down assay combined with silver staining and Western blot were used to detect the binding of potentially methylated fragments to recognized proteins.RESULTS:METTL3 inhibited the adipogenesis of MSCs in an AKT1/PPARγ-dependent manner,and mediated the protein expression of AKT1 in an m6A-YTHDF2-dependent manner.YTHDF2 recognized and bound to coding sequence(CDS)of m6A-AKT1,and reduced its expression,which inhibited the adipogenesis of MSCs.CONCLUSION:The m6A methylase METTL3 regulates the adipo-genic differentiation of human bone marrow MSCs through YTHDF2/AKT1/PPARγ,providing a theoretical basis for the identification of new targets for acute myeloid leukemia treatment from the perspective of tumor microenvironment.

Objective:To observe the effectiveness and safety of pars plana vitrectomy (PPV) combined with inner limiting membrane (ILM) removal and 41G microneedle subretinal injection of balanced salt solution (BSS) in the treatment of refractory macular hole.Methods:A prospective clinical study. From January to June 2023, 20 cases (20 eyes) of refractory macular hole patients diagnosed through examination at The Affiliated Eye Hospital of Nanchang University were included in the study. The basal diameter of the affected eye's basal diameter (BD) was >1 000 μm. Macular hole index (MHI) was <0.5. The affected eye received treatment with 23G PPV combined with ILM removal and 41G microneedle subretinal injection of BSS. Best corrected visual acuity (BCVA), microperimetry, and optical coherence tomography angiography (OCTA) were performed before and 1, 2, 3, and 6 months after surgery for the affected eye. BCVA examination was performed using standard logarithmic visual acuity chart, and convert it to logarithmic minimum resolution angle (logMAR) visual acuity for statistical purposes. MP-3 microperimetry was used for micro view examination, record the mean sensitivity (MS) of the retinal within a 12° range of the fovea. OCTA was used to measure the area of the avascular zone of the macula (FAZ), perimeter of the FAZ (PERIM), retinal vascular length density (VLD), and vascular perfusion density (VPD). The changes in BCVA, MS, FAZ area, PERIM, VLD, VPD before and after surgery were compared and analyzed. After the same time, the closure of macular hole and the occurrence of complications after surgery were observed. Single factor analysis of variance was used to compare the observation indicators at different times before and after surgery. The correlation between various observation indicators and preoperative minimum diameter (MD), BD, and hiatus height at 6 months after surgery were analyzed using Pearson correlation analysis.Results:Among the 20 cases with 20 eyes, there were 2 males with 2 eyes and 18 females with 18 eyes. Age was (61.45±8.56) years old. The logMAR BCVA, MS, FAZ area, PERIM, VLD, and VPD of the affected eye were 1.46±0.21, (16.20±5.81) dB、(0.40±0.17) mm 2, (2.89±0.99) mm, (6.23±3.59) mm -1, (0.17±0.10)%, respectively. Six months after surgery, out of 20 eyes, macular hole closure and incomplete closure were 18 (90.0%, 18/20) and 2 (10.0%, 2/20) eyes, respectively. The logMAR BCVA, MS, FAZ area, PERIM, VLD, and VPD were 0.80±0.20, (22.20±4.60) dB, (0.18±0.10) mm 2, (1.83±0.80) mm, (9.54±2.88) mm -1, (0.31±0.14)%. Compared with before surgery, the differences were statistically significant ( P<0.05). The correlation analysis results showed a positive correlation ( P<0.05) between preoperative BD and postoperative 6-month PERIM and VPD. There was a negative correlation between preoperative MD and postoperative VLD at 6 months ( P<0.05). There was a negative correlation between preoperative MHI and logMAR BCVA and VPD at 6 months after surgery ( P<0.05). No complications such as elevated or decreased intraocular pressure, damage to retinal pigment epithelium, retinal hemorrhage, endophthalmitis, or retinal detachment occurred after surgery in all affected eyes. Conclusion:Minimally invasive PPV combined with ILM removal and 41G microneedle subretinal injection of BSS can effectively improve the closure rate of refractory macular hole patients in the short term, improve vision, and have good safety.

Objective:To observe the clinical effect of subretinal injection and intravitreal injection of conbercept in the treatment of polypoid choroidal vasculopathy (PCV).Methods:A prospective, randomized double-blind controlled study. From June 2022 to January 2023, 35 patients of 35 eyes with PCV diagnosed at Affiliated Eye Hospital of Nanchang University were included in the study. All patients were first-time recipients of treatment. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA) were performed in all affected eyes. BCVA was performed using an international standard visual acuity chart and converted to logarithmic minimum resolved angle (logMAR) visual acuity for statistical purposes. Enhanced depth imaging with OCT instrument was used to measure the macular retinal thickness (MRT), subfoveal choroidal thickness (SFCT), and pigment epithelium detachment (PED) height. Randomized numerical table method was used to divide the patients into subretinal injection group (group A) and vitreous cavity injection group (Group B), 18 cases with 18 eyes and 17 cases with 17 eyes, respectively. Comparison of age ( t=0.090), disease duration ( t=-0.370), logMAR BCVA ( t=?0.190), MRT ( t=0.860), SFCT ( t=0.247), and PED height ( t=?0.520) between the two groups showed no statistically significant difference ( P>0.05). The eyes of group A were given one subretinal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg), and subsequently administered on demand (PRN); eyes in group B were given intravitreal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg). The treatment regimen was 3+PRN. Lesions were categorized into active and quiescent according to the results of post-treatment OCT and BCVA. Active lesions were treated with intravitreal injection of conbercept at the same dose as before; stationary lesions were followed up for observation. BCVA and OCT were performed at 1, 2, 3, 6 and 9 months after treatment; ICGA was performed at 3, 6 and 9 months. BCVA, MRT, SFCT, and PED height changes before and after treatment were compared and observed in the affected eyes of the two groups. Independent sample t-test was used to compare between the two groups. Results:With the prolongation of time after treatment, the BCVA of the affected eyes in groups A and B gradually increased, and the MRT, SFCT, and PED height gradually decreased. Compared with group B, at 2, 3, 6, and 9 months after treatment, the BCVA of group A was significantly improved, and the difference was statistically significant ( t=?2.215, ?2.820, ?2.559, ?4.051; P<0.05); at 1, 2, 3, 6, and 9 months after treatment, the MRT of the affected eyes in group A ( t=?2.439, ?3.091, ?3.099, ?3.665, ?5.494), SFCT ( t=?3.370, ?3.058, ?3.268, ?4.220, ?4.121), and PED height ( t=?3.460, ?4.678, ?4.956, ?5.368, ?6.396) were significantly reduced, and the differences were statistically significant ( P<0.05). No complications such as intraocular inflammation, high intraocular pressure, or vitreous hemorrhage occurred in any of the affected eyes during or after treatment. Conclusion:Compared with the intravitreal injection of conbercept, the subretinal injection of conbercept can more effectively reduce the height of MRT, SFCT, PED height, and improve the visual acuity of the affected eyes with PCV.

Objective:To observe the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling and vitreous injection of mouse never growth factor (mNGF) in the high myopia macular hole (HMMH).Methods:A prospective study. Thirty-one patients (33 eyes) with HMMH diagnosed in Affiliated Eye Hospital of Nanchang University from August 2020 and February 2021 were selected. Before surgery, all included patients were subjected to a complete ophthalmologic evaluation including best corrected visual acuity (BCVA), optical coherence tomography (OCT), macular microperimetry and axial length measurement. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into logarithm of minimum resolution angle (logMAR) visual acuity during statistics. The included subjects were accepted the treatment of PPV combined with ILM peeling and vitreous injection of mNGF (combined group) or PPV united with ILM peeling (simple group), 15 cases with 16 eyes, 16 cases with 17 eyes, respectively. There were no significant differences in logMAR BCVA ( t=0.836), macular hole (MH) diameter (t=0.657), visual acuity (VA) ( t=0.176), the missing length of external limting membrane (ELM) and ellipsoid zone (EZ) ( t=1.255, 0.966) between two groups ( P>0.05). The follow-up time was at least 6 months. The BCVA, closure rate of MH, integrity of ELM and EZ and recovery of VA in macular area were compared and observed between the two groups after surgery. The logMAR BCVA, VA, the deficient lengths of ELM and EZ at different time points were compared by independent-samples t-test between two groups and analysis of variance was used to compare the repeated measurement data of each group. Fisher test was performed for comparison of count data. Results:Six months after surgery, MH closure rates in the simple group and the combined group were 88.24% (15/17) and 93.75% (15/16), respectively, with no significant difference ( P=0.523). At 3 and 6 months after surgery, the integrity recovery of ELM in the combined group was better than that in the simple group, and the difference was statistically significant ( t=2.282, 3.101; P<0.05). At 1, 3 and 6 months after surgery, EZ deletion length in the combined group was lower than that in the simple group, and the difference was statistically significant ( t=1.815, 2.302, 2.784; P<0.05). Compared with 1 week after surgery, VA in macular area of the combined group increased at 1, 3 and 6 months, and the difference was statistically significant ( P=0.007, <0.001, <0.001). At 3 and 6 months after surgery, VA in macular area of affected eyes in the combined group was higher than that in the simple group, and the difference was statistically significant ( t=1.897, 2.250; P<0.05). There was an interaction effect between the surgical method and the follow-up time. The postoperative time was prolonged, and the VA in macular area was decreased in the simple group and increased in the combined group, with statistical significance ( F=12.963, P<0.001). The BCVA and BCVA changes in the two groups increased with the extension of postoperative time. The improvement of BCVA and the difference of BCVA changes in the combined group were significantly higher than those in the simple group at different time points after surgery, with statistically significant differences ( F=12.374, 21.807, 5.695, 4.095; P<0.05). Conclusion:PPV combined with ILM peeling and vitreous injection of mNGF is more effective than PPV with ILM peeling for HMMH, improving both anatomical and functional outcomes.

Objective:To observe the effect of combined operation of internal and external surgery for intraocular hemorrhage of polypoidal choroidal vascular disease (PCV).Methods:Retrospective clinical research. From January to August 2018, 14 eyes of 14 patients with PCV combined with vitreous hemorrhage (VH) with hemorrhagic retinal detachment confirmed by eye examination at the Second Affiliated Hospital of Nanchang University were enrolled in this study. The average disease course was 1.12±0.68 months. The visual acuity decreased from 2 to 14 days. The average time from hemorrhagic retinal detachment to surgery was 6.32±2.82 d. There were 9 eyes with BCVA of light sensing, 3 eyes of hand movement, and 2 eyes of counting fingers. The average macular foveal thickness (CFT) was 564.6±102.2 μm. The range of retinal detachment involves equal or greater than 2 quadrants. 23G vitrectomy surgery was used to remove VH, and subretinal hemorrhage was drained through external scleral drainage to reset the retina. One week and 1 and 2 months after the operation, the eyes were injected with 0.05 ml of ranibizumab in the vitreous cavity. The average follow-up time after surgery was 6.24±1.16 months. One week after the operation, 1, 3, and 6 patients were examined with the same equipment and methods before the operation to observe the condition of BCVA, CFT, intraocular pressure and retinal reattachment. Non-parametric tests were used to compare BCVA before and after surgery.Results:VH was completely cleared in all eyes, and no iatrogenic retinal hole appeared during the operation. Six months after the operation, there were 1 eye with BCVA of hand movement, 1 eye of counting fingers, 8 eyes of 0.1, 2 eyes of 0.2 and 2 eyes of over than 0.2; the average CFT was 336.4±54.8 μm. Compared with before surgery, the BCVA was significantly improved ( Z=-3.711, P=0.000), the CFT was significantly decreased ( t=3.212, P=0.006). OCT examination showed that the macular morphology and structure were clearly visible. Of the 14 eyes, 13 eyes were reattached, 1 eye was detached again after silicone oil removal. Intraocular pressure increased in 3 eyes within 1 week after surgery, including 1 eye with a small amount of blood in the anterior chamber. No recurrent VH was found in all eyes during follow-up. Conclusions:Combined internal and external surgery for PCV combined with VH with hemorrhagic retinal detachment is safe and effective.