Membrane remodeling properties of the Parkinson's disease protein LRRK2.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson's disease. LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell-free systems, we report that purified LRRK2 directly binds acidic lipid bilayers with a preference for highly curved bilayers. While this binding is nucleotide independent, LRRK2 can also deform low-curvature liposomes into narrow tubules in a guanylnucleotide-dependent but Adenosine 5'-triphosphate-independent way. Moreover, assembly of LRRK2 into scaffolds at the surface of lipid tubules can constrict them. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs.

HBV-infected hepatocellular carcinoma can be robustly classified into three clinically relevant subgroups by a novel analytical protocol.

Liver cancer is the third leading cause of cancer-related death worldwide, and hepatocellular carcinoma (HCC) accounts for a relatively large proportion of all primary liver malignancies. Among the several known risk factors, hepatitis B virus (HBV) infection is one of the important causes of HCC. In this study, we demonstrated that the HBV-infected HCC patients could be robustly classified into three clinically relevant subgroups, i.e. Cluster1, Cluster2 and Cluster3, based on consistent differentially expressed mRNAs and proteins, which showed better generalization. The proposed three subgroups showed different molecular characteristics, immune microenvironment and prognostic survival characteristics. The Cluster1 subgroup had near-normal levels of metabolism-related proteins, low proliferation activity and good immune infiltration, which were associated with its good liver function, smaller tumor size, good prognosis, low alpha-fetoprotein (AFP) levels and lower clinical stage. In contrast, the Cluster3 subgroup had the lowest levels of metabolism-related proteins, which corresponded with its severe liver dysfunction. Also, high proliferation activity and poor immune microenvironment in Cluster3 subgroup were associated with its poor prognosis, larger tumor size, high AFP levels, high incidence of tumor thrombus and higher clinical stage. The characteristics of the Cluster2 subgroup were between the Cluster1 and Cluster3 groups. In addition, MCM2-7, RFC2-5, MSH2, MSH6, SMC2, SMC4, NCPAG and TOP2A proteins were significantly upregulated in the Cluster3 subgroup. Meanwhile, abnormally high phosphorylation levels of these proteins were associated with high levels of DNA repair, telomere maintenance and proliferative features. Therefore, these proteins could be identified as potential diagnostic and prognostic markers. In general, our research provided a novel analytical protocol and insights for the robust classification, treatment and prevention of HBV-infected HCC.

tRNA modification enzyme MiaB connects environmental cues to activation of Pseudomonas aeruginosa type III secretion system.

Pseudomonas aeruginosa, a major inhabitant of numerous environmental reservoirs, is a momentous opportunistic human pathogen associated with severe infections even death in the patients suffering from immune deficiencies or metabolic diseases. Type III secretion system (T3SS) employed by P. aeruginosa to inject effector proteins into host cells is one of the pivotal virulence factors pertaining to acute infections caused by this pathogen. Previous studies showed that P. aeruginosa T3SS is regulated by various environmental cues such as calcium concentration and the host signal spermidine. However, how T3SS is regulated and expressed particularly under the ever-changing environmental conditions remains largely elusive. In this study, we reported that a tRNA modification enzyme PA3980, designated as MiaB, positively regulated T3SS gene expression in P. aeruginosa and was essential for the induced cytotoxicity of human lung epithelial cells. Further genetic assays revealed that MiaB promoted T3SS gene expression by repressing the LadS-Gac/Rsm signaling pathway and through the T3SS master regulator ExsA. Interestingly, ladS, gacA, rsmY and rsmZ in the LadS-Gac/Rsm signaling pathway seemed potential targets under the independent regulation of MiaB. Moreover, expression of MiaB was found to be induced by the cAMP-dependent global regulator Vfr as well as the spermidine transporter-dependent signaling pathway and thereafter functioned to mediate their regulation on the T3SS gene expression. Together, these results revealed a novel regulatory mechanism for MiaB, with which it integrates different environmental cues to modulate T3SS gene expression in this important bacterial pathogen.

Tilianin enhances the antitumor effect of sufentanil on non-small cell lung cancer.

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 µM, and the IC50 of Tilianin for H1299 cells was 44.6 µM. Functionally, 0.5 nM sufentanil and 10 µM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 µM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 µM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 µM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.

PREDICTIVE FACTORS ASSOCIATED WITH THE VISUAL PROGNOSIS AFTER SURGERY FOR IDIOPATHIC VITREOMACULAR TRACTION.

PURPOSE: To investigate the predictive factors for postsurgical visual prognosis in patients with vitreomacular traction (VMT). METHODS: This retrospective study enrolled 31 eyes from 29 patients who underwent vitrectomy for idiopathic VMT with a follow-up period of ≥3 months. The VMT was divided into three grades based on optical coherence tomography images: Grade 1 denoted partial vitreomacular separation with foveal attachment; Grade 2 exhibited intraretinal cysts or cleft with grade 1 findings; and Grade 3 was Grade 2 plus the subretinal fluid. RESULTS: Three eyes developed a full-thickness macular hole after surgery, all of which were Grade 3 patients. In the rest 28 eyes, the mean postoperative follow-up period was 23.3 ± 25.8 months. The postoperative central foveal thickness ( P = 0.001) and final best-corrected visual acuity (BCVA; P < 0.001) were both significantly improved from baseline. Fifteen eyes (53.8%) gained ≥ two Snellen lines. Multilinear regression analysis showed that the worse the baseline BCVA ( P = 0.004), or the more advanced the VMT grade ( P = 0.049), the worse the final BCVA. Baseline BCVA was negatively associated with the postoperative visual improvement ( P < 0.001). Those Grade 3 patients with baseline Snellen BCVA of ≥20/40 were more likely to achieve a final Snellen BCVA of ≥20/25 ( P = 0.035). CONCLUSION: The VMT grade is an important predictive factor for the postsurgical visual prognosis. Surgical intervention should be performed as early as possible for Grade 3 patients to prevent further disease progression and maximize the postsurgical visual benefit.

Foveal Microstructure and Visual Outcomes after Pars Plana Vitrectomy in Patients with Different Types of Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of this study was to evaluate the clinical characteristics and surgical outcomes of the epiretinal membrane foveoschisis (ERM-FS) with different morphological types. METHODS: This retrospective observational study reviewed 44 consecutive ERM-FS patients who underwent ERM surgery. According to the optical coherence tomography images, ERM-FS was classified into three groups: group A, FS crossed the fovea with the foveola elevated; group B, FS located at the foveal edges with a near-normal central foveal point thickness; and group C, FS with undermined foveal edges with a near-normal central foveal point thickness. RESULTS: There were 10 eyes in group A, 20 eyes in group B, and 14 eyes in group C. Preoperatively, eyes in group A had the best best-corrected visual acuity (BCVA), the thickest central foveal point thickness, and the highest ellipsoid zone (EZ) intact rate among the three groups. After surgery, a resolution of foveoschisis was observed in 40.0%, 45.0%, and 50.0% of the eyes in group A, group B, and group C (p = 0.928), respectively. BCVA was significantly improved postoperatively. Although there was no significant difference in BCVA among the three groups at 1 month postoperatively, BCVA of group A was the best at 4 and 10 months. Correlation analysis indicated that the type of ERM-FS, baseline BCVA, central foveal point thickness, and postoperative EZ continuity (all p < 0.05) were important factors for the final BCVA. CONCLUSIONS: The damage to the retinal structure and visual function was milder in group A ERM-FS. Our study emphasized the necessity of OCT-based subtyping in patients with ERM-FS.

Fourier Ptychographic Neural Network Combined with Zernike Aberration Recovery and Wirtinger Flow Optimization.

Fourier ptychographic microscopy, as a computational imaging method, can reconstruct high-resolution images but suffers optical aberration, which affects its imaging quality. For this reason, this paper proposes a network model for simulating the forward imaging process in the Tensorflow framework using samples and coherent transfer functions as the input. The proposed model improves the introduced Wirtinger flow algorithm, retains the central idea, simplifies the calculation process, and optimizes the update through back propagation. In addition, Zernike polynomials are used to accurately estimate aberration. The simulation and experimental results show that this method can effectively improve the accuracy of aberration correction, maintain good correction performance under complex scenes, and reduce the influence of optical aberration on imaging quality.

Inhibitory interaction of flavonoids with organic anion transporter 3 and their structure-activity relationships for predicting nephroprotective effects.

The organic anion transporter 3 (OAT3), an important renal uptake transporter, is associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OAT3 inhibitors with little toxicity in natural products, especially flavonoids, in reducing OAT3-mediated AKI is of great value. The five strongest OAT3 inhibitors from the 97 flavonoids markedly decreased aristolochic acid I-induced cytotoxicity and alleviated methotrexate-induced nephrotoxicity. The pharmacophore model clarified hydrogen bond acceptors and hydrophobic groups are the critical pharmacophores. These findings would provide valuable information in predicting the potential risks of flavonoid-containing food/herb-drug interactions and optimizing flavonoid structure to alleviate OAT3-related AKI.

Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells.

Adoptive cell therapy (ACT) with expanded tumor-infiltrating lymphocytes (TIL) or TCR gene-modified T cells (TCR-T) that recognize mutant KRAS neo-antigens can mediate tumor regression in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (Tran et al in N Engl J Med, 375:2255-2262, 2016; Leidner et al in N Engl J Med, 386:2112-2119, 2022). The mutant KRAS-targeted ACT holds great potential to achieve durable clinical responses for PDAC, which has had no meaningful improvement over 40 years. However, the wide application of mutant KRAS-centric ACT is currently limited by the rarity of TIL that recognize the mutant KRAS. In addition, PDAC is generally recognized as a poorly immunogenic tumor, and TILs in PDAC are less abundant than in immunogenic tumors such as melanoma. To increase the success rate of TIL production, we adopted a well-utilized K562-based artificial APC (aAPC) that expresses 4-1BBL as the costimulatory molecules to enhance the TIL production from PDCA. However, stimulation with K562-based aAPC led to a rapid loss of specificity to mutant KRAS. To selectively expand neo-antigen-specific T cells, particularly mKRAS, from the TILs, we used tandem mini gene-modified autologous T cells (TMG-T) as the novel aAPC. Using this modified IVS protocol, we successfully generated TIL cultures specifically reactive to mKRAS (G12V). We believe that autologous TMG-T cells provide a reliable source of autologous APC to expand a rare population of neoantigen-specific T cells in TILs.

The ubiquitination of rag A GTPase by RNF152 negatively regulates mTORC1 activation.

mTORC1 is essential for regulating cell growth and metabolism in response to various environmental stimuli. Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome. However, the mechanism by which amino acids regulate Rag activation remains not fully understood. Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The mutation of RagA ubiquitination sites abolishes this effect of RNF152 and enhances the RagA-mediated activation of mTORC1. Ubiquitination by RNF152 generates an anchor on RagA to recruit its inhibitor GATOR1, a GAP complex for Rag GTPases. RNF152 knockout results in the hyperactivation of mTORC1 and protects cells from amino-acid-starvation-induced autophagy. Thus, this study reveals a mechanism for regulation of mTORC1 signaling by RNF152-mediated K63-linked polyubiquitination of RagA.

Changes in foveal photoreceptor integrity after idiopathic epiretinal membrane surgery and its relationship with visual outcomes.

PURPOSE: To investigate the changes in the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) integrity and their relationship with visual outcomes after idiopathic epiretinal membranes peeling. METHODS: Clinical records of 150 eyes from 144 consecutive patients who underwent vitrectomy were reviewed. The status of IZ, EZ, and ELM was assessed by spectral-domain optical coherence tomography at baseline and 1, 4, 10, and 24 months postoperatively. RESULTS: Sixty-one eyes presented with photoreceptor layer disruption preoperatively, and IZ disruption (40.7%) was the primary type. The best-corrected visual acuity (BCVA) in the photoreceptor disruption group was significantly lower than that in the intact group at baseline and the final follow-up. Of them, ELM + EZ + IZ disruption showed the worst BCVA (P = 0.001). After surgery, 62 eyes were observed with disruption aggravated. EZ + IZ disruption (51.0%) was the most frequent type at 1 month postoperatively. The eyes with longer symptom duration, better BCVA, earlier stage, thinner CFT at baseline, and combined cataract surgery more tended to be observed with photoreceptor damage progressed after surgery (P < 0.05). There was no significant difference in the final BCVA between the eyes with and without damage progressed (P = 0.332). Finally, 28.1% of the eyes recovered photoreceptor continuity. The eyes with foveal photoreceptor integrity restored had better BCVA than those remaining discontinuous (P < 0.001). CONCLUSION: ERM-induced photoreceptor disruption mainly manifests as IZ disruption and has a negative effect on BCVA, whereas surgery mainly causes EZ and IZ disruption, which does not have a significant impact on the final BCVA.

Clinical features of idiopathic epiretinal membrane in children and the factors influencing postoperative visual acuity.

PURPOSE: To describe the characteristics and surgical outcomes of idiopathic epiretinal membrane (iERM) in children and to determine the factors associated with postoperative visual acuity (VA). METHODS: We retrospectively reviewed the medical records of 17 patients with iERM (age, < 18 years) who had undergone ERM surgery from 2009 to 2021. Spectral-domain optical coherence tomography features were documented. The eyes with iERMs involving the fovea were assigned to the localized and diffused groups depending on the morphological description of the membrane. Multiple linear regression analysis was used to explore the factors associated with the final VA. RESULTS: The mean age was 9.2 ± 3.8 years. The mean follow-up period was 38.9 ± 45.4 months. After surgery, the central foveal thickness and the best-corrected VA (BCVA) improved significantly (all, P < 0.05). Fourteen eyes with iERMs showed involvement of the foveal area (localized group, six eyes; diffused group, eight eyes). There were no significant differences in the preoperative BCVA between the two groups (P = 0.064). However, the final BCVA was better in the diffused group than in the localized group (P = 0.043). Multiple regression analysis indicated that the localized membrane (P = 0.042) and lower preoperative BCVA (P = 0.043) were factors associated with a worse final VA in pediatric iERMs. CONCLUSIONS: Surgical removal of ERM showed a high anatomical and functional success rate in children. In pediatric patients with iERMs involving the fovea, a good VA was more common when the membrane was diffused than when it was localized.

CLINICAL CHARACTERISTICS AND SURGICAL PROGNOSIS OF IDIOPATHIC MACULAR HOLES WITH EPIRETINAL PROLIFERATION.

PURPOSE: To investigate the clinical features and surgical outcomes of idiopathic macular holes with epiretinal proliferation (EP). METHODS: This retrospective study included 282 eyes of 269 consecutive patients who underwent vitrectomy for idiopathic macular holes. Clinical demographic data, baseline and postoperative retinal microstructure features on optical coherence tomography images, best-corrected visual acuity, and postoperative closure rate were compared between eyes with and without EP. RESULTS: EP was identified in 38 of 282 eyes (13.5%). Eyes with EP had a significantly longer symptom duration ( P = 0.019), higher frequency of pseudophakic conditions ( P = 0.034), presence of epiretinal membrane ( P < 0.001), and a larger base diameter ( P = 0.014) than those without EP. In addition, compared with eyes without EP, those with EP had a higher percentage of U-type closure ( P = 0.047) and a thicker central fovea ( P = 0.012) at 1 month postoperatively and a significantly lower frequency of ellipsoid zone disruption ( P = 0.033) and outer foveolar lucency ( P = 0.021) and a thicker central fovea ( P = 0.004) at 10 months postoperatively. CONCLUSION: The presence of EP represents a more chronic pathogenic process but has no negative effect on postoperative outcomes and can even facilitate anatomical recovery after surgery.

DIFFERENCES IN ANATOMICAL AND VISUAL OUTCOMES AMONG THREE INTERNAL LIMITING MEMBRANE TECHNIQUES TREATING EXTRA-LARGE IDIOPATHIC MACULAR HOLES.

PURPOSE: To compare the anatomical and visual outcomes of extra-large idiopathic macular holes treated with internal limiting membrane peeling and two inverted internal limiting membrane flap techniques, namely insertion and cover technique. METHODS: Patients with idiopathic macular holes (minimum linear diameter ≥ 650 µm) were divided into peeling group, insertion group, and cover group. The initial closure rate, final length of external limiting membrane and ellipsoid zone recovery, and best-corrected visual acuity were evaluated. RESULTS: A total of 124 eyes were included, and the average follow-up was 7.2 months. All the baseline characteristics were comparable among the three groups. Initial closure rate of the peeling group, the insertion group, and the cover group was 65.0% (26/40), 97.6% (41/42), and 90.5% (38/42), respectively (P < 0.001). In closed idiopathic macular holes, the peeling group and the cover group exhibited significantly longer length of external limiting membrane recovery than the insertion group (P < 0.001), and the peeling group exhibited significantly longer length of ellipsoid zone recovery than the other two groups (P = 0.021). The peeling group and the cover group exhibited significantly better best-corrected visual acuity improvement than the insertion group (P = 0.009). CONCLUSION: For extra-large idiopathic macular holes, cover technique surpasses internal limiting membrane peeling technique in closure rate and outperforms insertion technique in anatomical and functional recovery, whereas insertion technique may adversely affect the recovery of foveal microstructure and best-corrected visual acuity.

COMPARISON OF AIR VERSUS PERFLUOROPROPANE INTRAOCULAR TAMPONADE COMBINED WITH VITRECTOMY FOR THE TREATMENT OF MACULAR HOLE IN HIGH MYOPIA.

PURPOSE: To compare the efficacy of air and perfluoropropane (C3F8) with pars plana vitrectomy (PPV) in highly myopic macular holes (HMMHs) and explore the factors related to surgical prognosis. METHODS: A retrospective comparison of a consecutive series of HMMHs undergone vitrectomy and internal limiting membrane peeling. According to tamponade type, they were divided into air group and C3F8 group, which were further divided into subgroups based on hole diameter or axial length (AXL). Anatomical and functional outcomes were compared between tamponades. Related factors of initial closure rate and postoperative best-corrected visual acuity (BCVA) were analyzed by logistic regression. RESULTS: The baseline characteristics in air group (n = 63) and C3F8 group (n = 37) were similar except the age of air was older ( P = 0.019). The mean follow-up period was 17.16 ± 17.97 months. After surgery, the initial closure rate of air group was 85.7% and that of C3F8 group was 83.7% ( P = 0.780). And the initial closure rate showed no difference between tamponades in the same subgroup classified by hole diameter or AXL (all P > 0.05). Postoperative BCVA improved significantly in both groups ( P < 0.001), but no difference between them ( P = 0.793). Logistic regression showed that age, minimum linear diameter, and AXL were risk factors of initial closure rate, and preoperative BCVA was the only factor associated with postoperative BCVA (all P < 0.05). CONCLUSION: With a long-term follow-up of HMMH, we found air had a similar tamponade effect anatomically and functionally compared with C3F8. Air may also be a good choice for patients with HMMH.

Inhibitory interaction of flavonoids with organic cation transporter 2 and their structure-activity relationships for predicting nephroprotective effects.

Organic cation transporter 2 (OCT2) is mainly responsible for the renal secretion of various cationic drugs, closely associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OCT2 inhibitors with little toxicity in natural products in reducing OCT2-mediated AKI is of great value. Flavonoids are enriched in various vegetables, fruits, and herbal products, and some were reported to produce transporter-mediated drug-drug interactions. This study aimed to screen potential inhibitors of OCT2 from 96 flavonoids, assess the nephroprotective effects on cisplatin-induced kidney injury, and clarify the structure-activity relationships of flavonoids with OCT2. Ten flavonoids exhibited significant inhibition (>50%) on OCT2 in OCT2-HEK293 cells. Among them, the six most potent flavonoid inhibitors, including pectolinarigenin, biochanin A, luteolin, chrysin, 6-hydroxyflavone, and 6-methylflavone markedly decreased cisplatin-induced cytotoxicity. Moreover, in cisplatin-induced renal injury models, they also reduced serum blood urea nitrogen (BUN) and creatinine levels to different degrees, the best of which was 6-methylflavone. The pharmacophore model clarified that the aromatic ring, hydrogen bond acceptors, and hydrogen bond donors might play a vital role in the inhibitory effect of flavonoids on OCT2. Thus, our findings would pave the way to predicting the potential risks of flavonoid-containing food/herb-drug interactions in humans and optimizing flavonoid structure to alleviate OCT2-related AKI.

Internal Limiting Membrane Peeling or Inverted Flap Technique Combined with Air Tamponade in the Treatment of Macular Holes in High Myopia.

PURPOSE: The aim of this study was to analyze the anatomical and visual outcomes after internal limiting membrane (ILM) peeling or ILM flap insertion in highly myopic macular holes (HMMHs) and try to compare these two surgical techniques in large HMMHs. METHODS: This is a retrospective, consecutive series study of patients with HMMH undergone vitrectomy from September 2016 to January 2021. We observed the outcomes of the HMMHs with ILM peeling and ILM flap insertion, respectively. Binary logistic regression and receiver operating characteristic (ROC) curve were used to analyze the relationship between the minimum linear diameter (MLD) of macular hole and the initial closure rate in ILM peeling group. Finally, we compared the surgical outcomes between these two surgical techniques in large HMMHs. RESULTS: There were 69 HMMHs using ILM peeling with a mean MLD of 423.55 ± 190.99 µm and 33 HMMHs using ILM flap insertion with a mean MLD of 600.79 ± 187.85 µm. The initial type I closure rate was 86.9% (60/69) and 81.8% (27/33), respectively. MLD had a good correlation with the initial closure rate in HMMHs with ILM peeling (p = 0.046). The large HMMH (MLD >461.5 µm obtained by ROC curve) was present in 26 eyes with each surgical technique, and there was no significant difference of baseline characteristics between them. In large HMMHs, the initial closure rate of ILM peeling was 73.0% and that of ILM flap insertion was 84.6% (p = 0.499). Postoperative best-corrected visual acuity (BCVA) improved significantly in both groups (p < 0.001), and the BCVA at last follow-up was better in closed large HMMHs with ILM peeling (p = 0.034). CONCLUSION: In HMMHs with ILM peeling, the initial closure rate was decreased when MLD >461.5 µm. ILM peeling may obtain better functional prognosis in eyes with closed large macular holes compared with ILM flap insertion.

Comparison of Different Internal Limiting Membrane Peeling Sizes for Idiopathic Macular Holes: A Systematic Review and Meta-Analysis.

BACKGROUND: Although internal limiting membrane (ILM) peeling facilitates macular hole (MH) closure and reduces late hole reopening, it brings some detrimental consequences to the retinal microstructure and functional outcomes. So far, previous studies have not reached a consensus on the optimal ILM peeling size. OBJECTIVES: The objective of this study was to evaluate the outcomes of different ILM peeling sizes for idiopathic MHs. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, and WANFANG were searched until April 10, 2022. Studies in English or Chinese that compare the effects of two ILM peeling sizes (>2 disk diameters [DDs] vs. ≤2DD) for idiopathic MHs were included. The overall closure rate, postoperative best-corrected visual acuity (BCVA), type 1 closure, and adverse events were extracted. BCVA was converted to logarithm of the minimum angle of resolution (LogMAR). RESULTS: Seven eligible studies (560 eyes) including 3 randomized clinical trials, 3 prospective trials, and one retrospective cohort were included. Pooled results showed a significantly better postoperative BCVA (mean difference = -0.16; 95% confidence interval [CI]: -0.27 to -0.04; LogMAR) and higher type 1 closure rate (risk ratio [RR] = 1.24; 95% CI: 1.08-1.43) in eyes with ILM peeling >2DD than those with peeling ≤2DD. No significant difference was found in overall closure rate and adverse events between the two groups. Subgroup analysis indicated that in MHs >400 µm, peeling >2DD helped obtain a better postoperative BCVA (mean difference = -0.17; 95% CI: -0.29 to -0.04; LogMAR) and higher frequency of type 1 closure (RR = 1.25; 95% CI: 1.03-1.51). CONCLUSIONS: Peeling >2DD shares similar safety level with peeling ≤2DD and has a superiority of facilitating visual recovery. Larger ILM peeling may be more beneficial for large MHs.

Morphological Characteristics of Foveal Pit Base and Its Impact on Visual Acuity in Macular Pseudoholes.

INTRODUCTION: To investigate the characteristics of macular pseudoholes (MPHs) with different foveal profiles and their impact on preoperative and postoperative visual acuity (VA). METHODS: A retrospective review of 47 eyes from 46 consecutive patients with MPH who had undergone vitrectomy was conducted. The MPHs were classified into u-shape and v-shape according to the morphological description of the foveola base. The best-corrected visual acuity (BCVA), central foveal point thickness, parafoveal thickness, parafoveal inner and outer retinal thickness, stretched lamellar cleavage, microcystic macular edema (MME), disorganization of retinal inner layers (DRIL), and the integrity of outer retinal layers were recorded. RESULTS: The eyes in the v-shaped group (n = 31) had lower BCVA, thicker retinal thickness, more intraretinal cleavage, MME, and DRIL than the u-shaped (n = 16) group (all p < 0.05). Multiple regression analysis revealed that the morphology of the foveola base was significantly related to the preoperative BCVA (p = 0.025). The VA was significantly improved in both groups, and the improvement was greater in the v-shaped group (p = 0.024). No significant difference was found in the postoperative BCVA between the two groups (all p > 0.05). CONCLUSION: The v-shape, reflecting the stretch in the foveola, had a significant impact on preoperative BCVA. However, the VA was improved after surgery whatever their initial foveal profile.

Photoreceptor Outer Segment Loss at the Macular Hole Border: Clinical Characteristics and Surgical Prognosis.

INTRODUCTION: During macular hole (MH) formation, the vitreofoveal traction may lead to foveal neural tissue avulsion and consequent photoreceptor loss. However, the clinical significance of the photoreceptor outer segment disruption at the MH border remains unclear. This study aims to investigate the clinical features and surgical outcomes of MHs with photoreceptor outer segment disruption at the MH border. METHODS: This study retrospectively reviewed 86 eyes from 85 patients who underwent vitrectomy combined with internal limiting membrane peeling for idiopathic MHs. Baseline and postoperative best-corrected visual acuity (BCVA) and foveal microstructure on optical coherence tomography images were compared between eyes with smooth and bumpy morphology, the latter of which was defined as those with an uneven and irregular surface with evident lumps and indentations at the MH border. RESULTS: The bumpy morphology was identified in 59 of 86 eyes (68.9%). At baseline, eyes with a bumpy MH morphology had a significantly larger minimum linear diameter (p = 0.043), a longer external limiting membrane defect (p = 0.013), and a worse baseline BCVA (p = 0.017) than those with a smooth morphology. Postoperatively, in a multivariate regression model adjusting preoperative confounding effects, eyes with bumpy borders were associated with a longer ellipsoid zone defect (p = 0.006) and a thinner central fovea (p = 0.002) at 1 month, and a thinner central fovea (p = 0.005) and a worse BCVA (p = 0.015) at 10 months. CONCLUSION: A severe photoreceptor outer segment loss is common at the MH border, which represents a chronic pathogenic process and may be an independent predictor for an incomplete photoreceptor recovery and worse long-term visual outcomes after surgery.