Clinical macular edema following uneventful cataract surgery in eyes without pre-existing fundus diseases: risk factors and treatment prognosis.

BACKGROUND: To investigate the risk factors and prognosis of clinical pseudophakic cystoid macular edema (PCME) after uneventful phacoemulsification surgery in patients without pre-existing fundus diseases. METHODS: This was a retrospective case-control study. Medical records between August 2020 and August 2023 were reviewed for patients who had no previous fundus diseases and developed clinical PCME. A control group was randomly chosen and the risk factors for PCME was analyzed by binary logistic regression. Structure and visual prognosis of the PCME cohort were observed and compared among subgroups undergoing different treatment measures. RESULTS: Forty-seven eyes of 47 patients with PCME were included. The development of PCME was associated with higher systolic blood pressure (OR, 1.048; 95%CI 1.002, 1.097; P = .042), no posterior vitreous detachment (OR, 0.215; 95%CI: 0.553, 0.887; P = .032) and shorter axial lengths (OR, 0.401; 95%CI 0.161, 0.997; P = .049) compared to controls. During a mean follow-up of 8.26 months, 36 eyes (76.6%) showed visual improvement with decreased macular thickness. Different treatment modalities, including observation, topical NSAIDs, and intervention therapy, have no significant differences on the visual prognosis (P = 1.000). However, the intervention group had a shorter recovery time compared to the observation group (28.6 vs. 45.9 days, P = .037). CONCLUSION: PCME remains an encountered morbidity in patients without pre-existing fundus diseases. Shorter axial lengths, absence of posterior vitreous detachment, and higher systolic blood pressure are risk factors of PCME. Active intervention failed to improve the prognosis of PCME but could shorten the recovery time.

Subthreshold micropulse laser therapy for early postoperative macular thickening following surgical removal of epiretinal membrane.

BACKGROUND: This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. METHODS: This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. RESULTS: An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 µm vs. -45.0 ± 46.9 µm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 µm vs. -19.7 ± 16.3 µm, P = 0.547) or 3-month (-36.9 ± 26.9 µm vs. -34.0 ± 20.1 µm, P = 0.678) follow-up. CONCLUSIONS: SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. TRIAL REGISTRATION: The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

A specific RIP3+ subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism.

Retinal neovascularization is a leading cause of severe visual loss in humans, and molecular mechanisms of microglial activation-driven angiogenesis remain unknown. Using single-cell RNA sequencing, we identified a subpopulation of microglia named sMG2, which highly expressed necroptosis-related genes Rip3 and Mlkl. Genetic and pharmacological loss of function demonstrated that hypoxia-induced microglial activation committed to necroptosis through the RIP1/RIP3-mediated pathway. Specific deletion of Rip3 gene in microglia markedly decreased retinal neovascularization. Furthermore, hypoxia induced explosive release of abundant FGF2 in microglia through RIP3-mediated necroptosis. Importantly, blocking signaling components of the microglia necropotosis-FGF2 axis largely ablated retinal angiogenesis and combination therapy with simultaneously blocking VEGF produced synergistic antiangiogenic effects. Together, our data demonstrate that targeting the microglia necroptosis axis is an antiangiogenesis therapy for retinal neovascular diseases.

Application of a New Monitoring Variable: Effects of Power Loss During Squat Training on Strength Gains and Sports Performance.

ABSTRACT: Zhang, M, Chen, L, Dai, J, Yang, Q, Huang, Z, He, J, Ji, H, Sun, J, and Li, D. Application of a new monitoring variable: Effects of power loss during squat training on strength gains and sports performance. J Strength Cond Res 38(4): 656-670, 2024-This study aimed to compare the effects of power loss (PL) autoregulated volume (PL10 and PL20) with standardized fixed-load (FL) prescription on strength, sports performance, and lean body mass (LBM). Thirty-five female basketball players from a sports college were randomly assigned to 3 experimental groups (PL10, n = 12; PL20, n = 12; and FL, n = 11, respectively) that performed a resistance training (RT) program with wave-like periodization for 10 weeks using the back squat exercise. Assessments performed before (Pre) and after (Post) intervention included assessed 1 repetition maximum (1RM), body composition, 20-m sprint (T20M), change of direction (COD), and jump performance, including countermovement jump with arm swing, maximum vertical jump, and reactive strength index. Three groups showed significant improvements in strength (effect size [ES]: PL10 = 2.98, PL20 = 3.14, and FL = 1.90; p < 0.001) and jump performance (ES: PL10 = 0.74, PL20 = 1.50, and FL = 0.50; p <0.05-0.001). However, PL10 and PL20 demonstrated different advantages in sports performance compared with FL (group × time interaction, p <0.05). Specifically, PL10 significantly improved COD performance (ES = -0.79 ∼ -0.53, p <0.01), whereas PL20 showed greater improvements in sprint (ES = -0.57, p <0.05) and jump performance (ES = 0.67-1.64, p <0.01-0.001). Moreover, PL10 resulted in similar gains to PL20 and beneficial improvements compared with FL in LBM, despite performing the least repetitions. Overall, the study indicates that power loss-based autoregulation induces greater gains in LBM and sports performance, as well as eliciting a higher efficiency dose response than standardized FL prescriptions, particularly for PL10. Therefore, incorporating PL monitoring in training programs is recommended, and further studies on power-based RT would be worthwhile.

Evaluation of combined epiretinal membrane removal with intravitreal triamcinolone injection utilizing ectopic inner foveal layer staging scheme.

OBJECTIVE: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. METHODS: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. RESULTS: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). CONCLUSION: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.

The enhancement of explosive power contributes to the development of anaerobic capacity: A comparison of autoregulatory progressive resistance exercise and velocity-based resistance training.

Objectives: Due to the character of the taekwondo, the adenosine triphosphate-phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players. Methods: A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; n = 15) and velocity-based resistance training (VBRT; n = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT). Results: (1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJPP), relative peak power of CMJ (CMJRPP), and total number of TAIKT (TAIKTTN) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnTPPT) and moderate effect sizes for peak power of WAnT (WAnTPP), relative peak power of WAnT (WAnTRPP), and fatigue index of TAIKT (TAIKTFI), whereas the APRE group exhibited small effect sizes for TAIKTFI. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnTPP and WAnTRPP, whereas APRE had a small advantage in CMJPP and CMJRPP. Conclusions: These findings suggest that APRE improved explosive power (CMJPP and CMJRPP) more, whereas VBRT improved anaerobic power output (WAnTPP and WAnTRPP) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnTPPT and TAIKTTN) and fatigue index (power drop of WAnT and TAIKTFI).

Anatomical and visual outcomes of fovea-sparing internal limiting membrane peeling with or without inverted flap technique for myopic foveoschisis.

BACKGROUND: Vitrectomy and peeling of the internal limiting membrane (ILM) was an effective therapeutic approach for myopic foveoschisis with progressive visual loss. This study investigated the anatomical and visual outcomes of fovea-sparing ILM peeling with or without the inverted flap technique for patients with symptomatic myopic foveoschisis (MF). METHODS: We retrospectively reviewed the clinical data of patients with MF. Vitrectomy with fovea-sparing ILM peeling and air tamponade was performed in all patients. The primary outcome measures included best-corrected visual acuity (BCVA), mean macular thickness (MMT), and central foveal thickness (CFT). Depending on whether an inverted ILM flap technique was utilized, further subgroup comparisons between the inverted flap group and the non-inverted flap group were conducted. RESULTS: Twenty-six eyes of 22 patients were included. Fifteen eyes were underwent fovea-sparing ILM peeling without inverted ILM flap and 11 of the 26 eyes were treated with fovea-sparing ILM peeling and an inverted ILM flap technique. In the mean follow-up period of 10.74 ± 4.58 months, a significant improvement in BCVA was observed from 0.97 ± 0.45 logMAR to 0.58 ± 0.51 logMAR (P < 0.01), during which the BCVA of 20 eyes (76.92%) improved and remained stable in 5 eyes (19.23%). Moreover, a positive correlation was also found between the preoperative BCVA and the postoperative BCVA (r = 0.50, P = 0.01). At the last visit, the final MMT decreased from 492.69 ± 209.62 µm to 234.73 ± 86.09 µm, and the CFT reduced from 296.08 ± 209.22 µm to 138.31 ± 73.92 µm (all P < 0.01). A subgroup analysis found no significant differences in BCVA, MMT, or CFT between the inverted and non-inverted flap groups (all P > 0.05). CONCLUSION: Fovea-sparing ILM peeling with or without inverted flap technique resulted in favorable visual and anatomical outcomes for the treatment of MF. An important factor affecting the postoperative visual outcome was the preoperative visual acuity. Our study found no significant difference between the presence and absence of the inverted ILM flap.

Diabetic retinopathy with extensively large area of capillary non-perfusion: characteristics and treatment outcomes.

BACKGROUND: Capillary non-perfusion is an important characteristic for diabetic retinopathy (DR) indicating microvascular damage and ischemia. Data on the description and treatment outcomes of DR with large area of non-perfusion are lacking to date. We aim to describe the characteristics and treatment outcomes in a series of patients with DR who presented extensively large area of capillary non-perfusion (LACNP). METHODS: Fundus fluorescein angiograms from medical charts in patients diagnosed with DR between Jan 2017 and Dec 2019 were retrospectively reviewed. Clinical data in eyes with LACNP including imaging and laboratory findings at the first presentation were analyzed. The LACNP was defined as over 70% area of capillary non-perfusion throughout the whole image retina. The mean follow-up duration was 12.4 ± 16.7 months. Follow-up data including extensive pan-retinal photocoagulation and surgical intervention and treatment outcomes were evaluated. RESULTS: A total of 43 eyes in 24 patients with LACNP were included, accounting for 3.3% of DR populations in the same period. The overall percentage of non-perfusion area was 79.1 ± 8.1%. All patients received proper control of diabetes and hypertension, and extensive pan-retinal laser photocoagulation. During the follow-up periods, 20 eyes (46.5%) developed severe neovascular complications, of which 15 eyes (34.9%) underwent vitrectomy and/or anti-glaucoma surgeries. Conservative therapies including glycemic control and supplemental laser photocoagulation were conducted in 23 eyes (53.5%) without neovascular complications. In the final follow-up, best corrected visual acuity improved or maintained stable in 19 eyes (44.2%) while deteriorated in 24 eyes (55.8%). CONCLUSIONS: The presence of LACNP is the hallmark of advanced DR and often indicates a poor visual outcome, although aggressive treatments may slow DR progression and maintain central vision for some time.

Repeatability and clinical use of pupillary light reflex measurement using RAPDx® pupillometer.

OBJECTIVE: To evaluate the repeatability of pupillary light reflex metrics measured by the RAPDx® dynamic pupillometer in healthy subjects and clinical application in patients with unilateral optic neuritis (ON). METHODS: Sixty eyes of 30 healthy volunteers were measured three times consecutively by the same technician. The amplitude of constriction (AC), the latency of constriction (LOC), the velocity of peak constriction (VC) of light-evoked pupillary constriction, RAPD score for amplitude and latency were measured using RAPDx® dynamic pupillometer. The repeatability of above metrics was assessed by the intraclass correlation coefficient (ICC) and coefficient of variation (Cov). Furthermore, pupillary light reflex measurements were performed in 48 eyes of 24 patients diagnosed with unilateral optic neuritis (ON). Interocular symmetry was evaluated both in the healthy subjects and the ON-involved patients. RESULTS: High repeatability of AC, LOC, and VC in healthy subjects was displayed, presenting with the ICC value over 0.80 and the Cov less than 8.00%. But the RAPD score for amplitude (ICC: 0.67) and RAPD score for latency (ICC: 0.65) showed only moderate repeatability. Furthermore, a slight declining trend was found in amplitude and peak velocity when continuous and multiple measurements in the healthy subjects. Good symmetry of the AC, LOC, and VC of pupillary light constriction between the two eyes was displayed in the healthy subjects (P > 0.05). By contrast, there was a distinct decrease of AC and VC (P < 0.01), and a mild increase of LOC (P < 0.01) in the ON-involved eye in direct pupillary light reflex. CONCLUSIONS: Pupillary light reflex measured by the RAPDx® pupillometer achieved overall good repeatability and interocular symmetry in healthy subjects. The device also presented decent preliminary results in patients with unilateral ON, suggesting its potential value to be developed as a tool in optic nerve diseases.

IL-17 signaling induces iNOS+ microglia activation in retinal vascular diseases.

Activation of microglia and inflammation-mediated vascular damages are suggested to play a decisive role in the pathogenesis of various retinopathies. The inducible nitric oxide synthase (iNOS) was required for activated microglia-mediated injuries. However, the induction mechanism of microglia activation during retinal vascular diseases is still elusive. Here we showed that IL-17 induced microglia activation with high expression of iNOS and promoted the development of retinal vascular diseases. IL-17-dependent activation of the STAT3-iNOS pathway was essentially required for microglia activation, which promoted endothelial cell growth and accelerated vascular leakage and leukostasis via IL-6 in vitro and in vivo. Taken together, our data provide novel mechanistic insights on microglia activation-mediated retinopathy, unveil the specific role of IL-17 on microglia, and define novel therapeutic targets for treating retinal vascular diseases.

Three-dimensional position of mandibular third molars and its association with distal caries in mandibular second molars: a cone beam computed tomographic study.

OBJECTIVE: To analyze the prevalence of distal caries in mandibular second molars (M2Ms) and its correlation with the three-dimensional position of mandibular third molars (M3Ms) by cone beam computed tomography (CBCT) images. MATERIALS AND METHODS: CBCT scans involving 421 M3Ms were assessed. The presence of distal caries of M2Ms, patient age and gender, impaction depths and mesial angulation of M3Ms, the cementoenamel junction (CEJ) distances and contact point localization, and the horizontal positions of M3Ms were assessed. Risk factors were identified by multivariate logistic regression analysis. RESULTS: The overall prevalence of distal caries in M2Ms was 31.6%. Mesial angulation (16°-75°) of M3Ms, contact point localization at or below the CEJ of M2Ms, and a buccal or lingual position of M3Ms relative to the molar line were identified as risk factors for the prevalence of distal caries in M2Ms (p < 0.05). Distal caries was more severe when the mesial angulation of M3Ms was 16°-75° (p < 0.05). CONCLUSIONS: Buccal or lingual position of M3Ms may represent a new risk factor for the distal caries in M2Ms. Mesial angulation (16°-75°) of M3Ms is a predictive parameter for both the presence and severity of distal caries in M2Ms. CLINICAL RELEVANCE: As the presence of distal caries in M2Ms is significantly associated with the three-dimensional position of M3Ms, watchful monitoring or prophylactic removal of M3Ms should be deliberated when M3Ms are mesially angulated (16°-75°), buccally or lingually positioned, and with the contact point localization at or below the CEJ of M2Ms.

Correlation between sub-Tenon's anesthesia and transient amaurosis during ophthalmic surgery.

PURPOSE: To verify the correlation between sub-Tenon's anesthesia and intraoperative visual loss in ophthalmic surgery. METHODS: Sixty-four patients underwent phacoemulsification combined pars plana vitrectomy under sub-Tenon's anesthesia. Participants were investigated about their light perception at several time points: before anesthesia, immediately after anesthesia, 10 min after anesthesia without any surgical intervention or microscope illumination, and after the whole surgery. Intraoperative amaurosis was determined as that a patient could not see any light from their operative eye. The incidence rate of amaurosis at different time points and among different anesthetists was analyzed. RESULTS: The rate of intraoperative amaurosis was 0%, 1.56%, 48.44%, and 95.31% at several time points, respectively: before anesthesia, immediately after anesthesia, 10 min after anesthesia without any surgical intervention or microscope light exposure during the interval, and immediately after the whole surgery, presenting a significantly time-dependent increase (P < 0.01). There was no correlation between the amaurosis and different diseases and anesthesiologists. The amaurosis was transient, and all operative eyes could perceive light on the first postoperative day. CONCLUSIONS: Sub-Tenon's anesthesia contributes to the intraoperative amaurosis during operation. Temporary interruption of optic nerve conduction by the anesthetic could be a credible explanation. The amaurosis is transient and reversible, requires no additional treatment, and should not be considered as a surgical complication.

Presence of isthmi in mandibular mesial roots and associated factors: an in vivo analysis.

PURPOSE: To investigate the prevalence of isthmi and middle mesial (MM) canals in the mesial roots of mandibular first molars (MFM) in a Mongoloid subpopulation and to evaluate their association with demographic and anatomic characteristics. METHODS: Cone-beam computed tomography (CBCT) images of 496 patients with 823 MFMs were selected and analyzed. The following data were collected: patient age and gender, side, presence and distribution of MM canal and isthmus, distance between mesiobuccal (MB) and mesiolingual (ML) orifices, and MB-ML root canal system (RCS) morphology. Logistic regression was used to determine the association between demographic and anatomic characteristics and the presence of isthmi in the apical third. RESULTS: The overall prevalence of isthmus and an MM canal in MFM was 64.6% and 10.8%, respectively. The highest prevalence of isthmi and MM canals was found in patients of ≤ 20 and of 41-60 years, respectively (p < 0.05). The prevalence of isthmi declines with age. A total of 41.3% of the MFMs had isthmi in the apical third of the mesial roots. Younger age, shorter MB-ML orifice distance, and Weine type II RCS increased the probability of the presence of an isthmus in the apical third (p < 0.05). CONCLUSION: The prevalence of isthmus in MFM is high in the subject population, but the prevalence of MM canals is not as high as previously reported. Demographic and anatomic characteristics could aid clinicians to better predict the presence of MM canal and an isthmus.

Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-ß.

BACKGROUND/AIMS: Platelet-derived growth factors (PDGFs) have emerged as pivotal in pathological angiogenesis, which is a hallmark of various tumors and retinal diseases. Here we evaluated the anti-angiogenic effect of imatinib, an inhibitor of PDGF receptors α and ß (PDGFR-α and -ß), in retinal neovascularization using an oxygen-induced retinopathy (OIR) model. METHODS: The OIR model was established and given imatinib or vehicle treatments daily from P12 to P16. At the peak of angiogenesis at P17, the neovascularization area was quantified on retinal whole-mounts with isolectin B4 staining. Immunofluorescence staining and western blots were used to determine the effect of imatinib on different vascular cells and the pathway molecules involved. RESULTS: Imatinib effectively suppressed pathological angiogenesis in OIR mice and reduced the number of all three types of vascular cells, including endothelial cells, pericytes, and smooth muscle cells. Moreover, the expression and activation of PDGFR-α and -ß were inhibited by imatinib. The imatinib-treated OIR mice presented with reduced expression of other potent pro-angiogenic factors such as VEGF and FGF2. No obvious retinal or systemic side effects were observed in the imatinib treatment group. CONCLUSIONS: Imatinib appears to be safe and effective in suppressing retinal neovascularization. Targeting PDGFs/PDGFRs may also be important for anti-angiogenic treatment and offer a viable alternative treatment for retinal angiogenic diseases.

Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration.

Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-ß and PDGFR-α, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.

NGF increases VEGF expression and promotes cell proliferation via ERK1/2 and AKT signaling in Müller cells.

PURPOSE: Nerve growth factor (NGF) is a classic neuroprotective factor that contributes to angiogenesis under pathological conditions, which might be mediated by the upregulation of vascular endothelial growth factor (VEGF). Retinal Müller cells are a critical source of growth factors, including NGF and VEGF, and express the receptor for NGF, indicating the functional significance of NGF signaling in Müller cells. The aim of this study is to explore the effect of NGF on the production of other growth factors and cellular proliferation in Müller cells and to further detect the potential mechanism of these effects. METHODS: Primary Müller cells from C57BL/6J mice were isolated and identified with glutamine synthetase (GS) immunofluorescence (IF), a specific marker for Müller cells. TrkA, a high affinity receptor for NGF, was detected with IF staining in the primary Müller cells. Then, the cultured cells were stimulated with recombinant mouse NGF, and the supernatants and the cellular lysate were collected at different time points. VEGF secretion in the supernatant was detected with an enzyme-linked immunosorbent assay (ELISA). The signaling activation in the Müller cells was accessed by western blot using specific phosphorylated antibodies. In addition, cell proliferation was analyzed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Furthermore, K252a, U0126, and LY294002, the inhibitors for TrkA, extracellular signal-regulated kinases 1/2 (ERK1/2), and phosphatidylinositol 3-kinase (PI3K)/AKT, respectively, were used in combination with NGF in the assays analyzing VEGF expression and cell proliferation. RESULTS: Primary mouse Müller cells were successfully cultured and confirmed with GS positive staining. The IF results showed that the TrkA receptor was abundantly expressed on Müller cells. The ELISA results revealed that NGF significantly promoted the production and secretion of VEGF in Müller cells after 12 or 24 h of stimulation, with more elevation after 24 h. Furthermore, NGF activated ERK1/2 and PI3K/AKT signaling, which was shown by the marked upregulation of phosphorylation in the western blot. As expected, K252a, the inhibitor of TrkA, a high-affinity NGF receptor, suppressed the activation, showing little phosphorylation of ERK1/2 and PI3K/AKT signaling. Importantly, the VEGF levels were decreased after the inhibitors for TrkA, ERK1/2, and PI3K/AKT were used compared with NGF alone. In addition, the MTT assay showed that NGF promoted the proliferation of the Müller cells, which was also blocked by the TrkA, ERK1/2, and PI3K/AKT inhibitors. CONCLUSIONS: The results showed that NGF enhanced the secretion of VEGF and promoted cell proliferation via the ERK1/2 and PI3K/AKT pathways in Müller cells, indicating that NGF is involved in angiogenesis-related factor generation and gliosis in Müller cells.

Refractive outcomes following simultaneous silicone oil removal and ciliary sulcus intraocular lens implantation.

PURPOSE: This study aimed to assess the refractive outcomes following the combined intervention of silicon oil (SO) removal and ciliary sulcus intraocular lens (IOL) implantation in aphakic eyes after phacovitrectomy. METHODS: A retrospective examination of medical records from patients who underwent a combined procedure of SO removal and ciliary sulcus IOL implantation from 2019 to 2022 was performed. The primary outcomes of interest included uncorrected distance visual acuity (UDVA), predictive error (PE) and mean absolute predictive error (MAE). Subgroup analyses were performed to compare outcomes between patients with and without intraoperative posterior capsulotomy. RESULTS: The cohort comprised 40 eyes from 40 patients, with a mean duration of SO tamponade of 5.17 ± 1.48 months. A significant improvement in UDVA was observed from 1.58 ± 0.31 logMAR to 0.99 ± 0.31 logMAR one month postoperatively (P < 0.01). The PE was -0.73 ± 0.86 diopters (D), and the MAE was 0.90 ± 0.67 D, with 37.50% and 57.50% of cases achieving PE within ±0.5 D and ±1.0 D, respectively. No significant differences in UDVA, PE, or MAE were found between the capsulotomy and non-capsulotomy subgroups (all P > 0.05). However, a lower proportion of eyes in the capsulotomy group achieved PE within ±1.0 D compared to the non-capsulotomy group one month postoperatively (38.90% vs. 72.70%, P = 0.03). CONCLUSIONS: The combined procedure of SO removal and sulcus IOL implantation resulted in a mild myopic shift in postoperative refraction. Intraoperative posterior capsulotomy seems to increase the lability of postoperative refractive outcomes.

Non-Apoptotic Programmed Cell Death as Targets for Diabetic Retinal Neurodegeneration.

Diabetic retinopathy (DR) remains the leading cause of blindness among the global working-age population. Emerging evidence underscores the significance of diabetic retinal neurodegeneration (DRN) as a pivotal biomarker in the progression of vasculopathy. Inflammation, oxidative stress, neural cell death, and the reduction in neurotrophic factors are the key determinants in the pathophysiology of DRN. Non-apoptotic programmed cell death (PCD) plays a crucial role in regulating stress response, inflammation, and disease management. Therapeutic modalities targeting PCD have shown promising potential for mitigating DRN. In this review, we highlight recent advances in identifying the role of various PCD types in DRN, with specific emphasis on necroptosis, pyroptosis, ferroptosis, parthanatos, and the more recently characterized PANoptosis. In addition, the therapeutic agents aimed at the regulation of PCD for addressing DRN are discussed.