To develop a poly(lactic-co-glycolic acid) (PLGA) nanoparticle system encapsulating the type II TGF-βreceptor (TβRII)-targeting aptamer S58 (PLGA-S58) and evaluate its ability to mitigate subconjunctival fibrosis after glaucoma filtration surgery. PLGA-S58 was prepared by double emulsion-solvent evaporation and characterized for morphology, size, encapsulation efficiency, andin vitrorelease. Uptake by human conjunctival fibroblasts (HConFs) was assessed by flow cytometry and confocal microscopy. In a TGF-β2-induced fibrotic model, cytocompatibility, proliferation, migration, and expression ofα-smooth muscle actin (α-SMA) and type I collagen were evaluated.In vivo, a rat glaucoma filtration surgery model was established, and S58 or PLGA-S58 was administered subconjunctivally at the filtration site. Bleb morphology and intraocular pressure (IOP) were monitored for 30 d, and tissue fibrosis was assessed by histology and immunofluorescence. PLGA-S58 nanoparticles were spherical with a hydrodynamic size of 255-295 nm and an encapsulation efficiency of ∼66%. PLGA-S58 showed sustained release over 7 d (∼71% cumulative release at 168 h) while preserving aptamer integrity. Compared with free S58, PLGA-S58 more effectively suppressed TGF-β2-induced HConF proliferation, migration, and fibrotic marker expression. In rats, PLGA-S58 formed a local depot detectable for ⩾7 d, produced more diffuse and longer-lasting filtering blebs, achieved greater and more stable IOP reduction over 30 d, and reduced collagen deposition andα-SMA-positive myofibroblast accumulation in the filtration area. PLGA-S58 enables sustained local delivery of a TβRII-targeting aptamer and improves antifibrotic efficacy and bleb function after filtration surgery, supporting translational potential as a safer alternative to cytotoxic antimetabolites.
Purpose: The purpose of this study was to evaluate the long-term intraocular pressure (IOP)-lowering efficacy, antifibrotic activity, and outflow patency of a hydroxyapatitecoated degradable magnesium (HA-Mg) glaucoma drainage implant in a chronic glaucoma rabbit model. Methods: Chronic glaucoma was induced by anterior chamber injection of a magnetic bead suspension, and glaucomatous damage was confirmed by retinal thinning and optic nerve injury. In a separate cohort, glaucomatous eyes were randomized to trabeculectomy (TL), sham surgery, or HA-Mg implantation (n = 6/group) and followed for 6 months. IOP and corneal diameter were monitored longitudinally, aqueous outflow was evaluated using intracameral trypan blue, and filtration tissues were examined histologically. Results: Modeled eyes maintained IOP at approximately 30 millimeters of mercury (mm Hg) for 6 weeks, accompanied by retinal thinning and optic nerve damage. After treatment, IOP in the HA-Mg group decreased below 21 mm Hg and remained significantly lower than in the sham and TL groups, in which IOP remained elevated or rebounded. Only HA-Mg-implanted eyes showed recovery of corneal diameter to baseline at 6 months. Trypan blue testing demonstrated persistent subconjunctival drainage in the HA-Mg group, and histology revealed reduced fibroblast proliferation, decreased collagen deposition, and preservation of a clear filtration pathway. Conclusions: The degradable HA-Mg implant was well tolerated, provided sustained IOP reduction, and maintained outflow patency while attenuating postoperative fibrosis, supporting its potential for clinical translation in glaucoma filtration surgery. Translational Relevance: A biodegradable HA-Mg drainage implant that sustains outflow and limits fibrosis may offer a safer and more durable alternative to permanent subconjunctival drainage devices.
Retinal ischemia reperfusion injury (RIRI) presents a complex pathological mechanism involving oxidative stress, neuroinflammation, and retinal ganglion cell (RGC) apoptosis, with current therapies limited by their inability to address these multifaceted cascades. To address this challenge, we engineered microenvironment-responsive nanoparticles, pZIF-8@Bai, by encapsulating baicalein (Bai) within a polydopamine-coated zeolitic imidazolate framework (ZIF-8), The pZIF-8@Bai nanoparticles achieved targeted combination therapy through a sustained-release mechanism, resulting in comprehensive retinal protection: attenuating oxidative damage, promoting microglial M2 polarization, and significantly inhibiting RGC apoptosis. Importantly, functional assessments demonstrated substantial recovery of a-wave and b-wave amplitudes in electroretinography (ERG) and enhanced P1-wave amplitudes in flash visual evoked potential (FVEP) recordings. Mechanistically, proteomic analysis revealed suppression of Nogo-A expression, which modulated NF-κB signaling and the intrinsic apoptotic pathway, involving caspase-8 inhibition and BCL-2/BAX balance restoration. These actions preserved retinal structural integrity and restored visual function, as confirmed by electroretinography, with excellent biosafety profiles, offering a promising multi-target therapeutic strategy for neurodegenerative retinal diseases.
The uveoscleral outflow pathway is one of the important pathways for aqueous humor outflow. Implanting ab interno glaucoma drainage devices through this pathway does not require conjunctival filtering bleb formation, thereby avoiding bleb-related complications. However, permanent drainage devices can easily cause damage to the corneal endothelium. We hypothesize that a novel ab interno supraciliary HA-Mg biodegradable glaucoma drainage plate through the uveoscleral pathway can reduce corneal endothelial cell damage, demonstrate an IOP-lowering effect, and form and maintain a physiological aqueous outflow pathway after complete degradation and absorption. Sixteen New Zealand white rabbits were randomly assigned to three groups: HA-Mg drainage plate group (10 right eyes), trabeculectomy group (6 right eyes), and control group (16 left eyes). Results showed that the intraocular pressure (IOP) in the ab interno plate group was significantly lower than in the other two groups within the first 20 weeks after surgery (P < 0.0001). After 21 weeks, the IOP in the ab interno plate group gradually returned to the levels of the other two groups. Within 5 months after surgery, the plate was completely degraded and absorbed, the aqueous humor drainage pathway extended to the supraciliary space at the anterior chamber angle, and a water sac-like gap formed above the ciliary body. At the 6th month postoperatively, the number of corneal endothelial cells in the ab interno supraciliary HA-Mg drainage plate group was 2446.0 ± 104.3, and in the control group was 2391.67 ± 49.6, revealing no statistically significant difference (t = −1.611, P = 0.168). In summary, the HA-Mg biodegradable glaucoma drainage plate placement in rabbits was well fixed in the supraciliary space. After 5 months of implantation, the internal drainage plate was completely absorbed, and the implantation procedure and degradation process did not cause damage to the corneal endothelial cells. Compared with the trabeculectomy group, the ab interno plate group maintained a significantly lower IOP for a longer period in this normotensive rabbit model. Although an aqueous humor drainage channel was formed after degradation, the IOP gradually returned to the levels of the control group.
BACKGROUND:Diabetic cataract is a common complication of diabetes, and current clinical management mainly relies on surgical intervention, with limited preventive strategies available. This study aimed to investigate whether liver-targeted low-intensity pulsed ultrasound (LIPUS) can prevent or delay the progression of diabetic cataract and to elucidate the underlying molecular mechanisms. METHODS:A type 2 diabetes mellitus rat model was established using a high-fat diet combined with streptozotocin. Animals were divided into Normal, Model, and LIPUS groups. The LIPUS group received liver irradiation (200 mW/cm2, 10 min/day for 30 days). Lens opacity was assessed using slit-lamp examination, and blood glucose, branched-chain amino acids (BCAAs), and PRKAR1A expression were measured. In vitro experiments included co-culture of hepatocytes (AML12) and lens epithelial cells (SRA01/04) and siRNA transfection assays. Statistical analysis was performed using independent-samples t-tests and two-way ANOVA. RESULTS:LIPUS significantly delayed the onset and progression of diabetic cataract, reduced blood glucose levels and hepatic/serum BCAAs, and restored PRKAR1A expression in lens epithelial cells. LIPUS also inhibited epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA. Knockdown of PRKAR1A reversed the inhibitory effect of LIPUS on EMT. Additionally, LIPUS improved liver and pancreatic histopathology without causing detectable tissue damage. CONCLUSION:LIPUS prevents diabetic cataract through dual mechanisms: improving glucose homeostasis and reducing BCAAs levels to restore PRKAR1A expression, thereby inhibiting EMT in lens epithelial cells. These findings suggest that LIPUS represents a safe and non-invasive strategy for diabetic cataract prevention and highlight BCAAs and glucose metabolism as potential therapeutic targets. ONE SENTENCE SUMMARY:This study demonstrates that targeted hepatic application of low-intensity pulsed ultrasound (LIPUS) effectively delays diabetic cataract progression in rats by suppressing lens epithelial cell EMT through dual mechanisms-directly lowering blood glucose and reducing hepatic BCAA production to restore PRKAR1A expression via the liver-lens axis-thereby offering a promising non-invasive preventive strategy that concurrently improves systemic glucose metabolism.
Staged bilateral trabeculectomy is common in glaucoma, yet the interval between first- and second-eye surgery is largely experience-based. Whether unilateral trabeculectomy induces a time-dependent inflammatory shift in the contralateral unoperated eye—potentially altering the perioperative milieu for second-eye surgery—remains unclear. We aimed to characterize the peak and recovery window of aqueous humor inflammatory mediators in the contralateral eye after unilateral trabeculectomy. Twelve New Zealand White rabbits (2.0 ± 0.25 kg; 6 males and 6 females) underwent unilateral trabeculectomy in the right eye; the left eye served as the fellow-eye control. Aqueous humor was collected bilaterally at baseline (Day − 14) and at 3 days, 1, 2, 4, 8, and 12 weeks postoperatively (50 µL/eye/time point; serial sampling). IL-6, IL-1β, TNF-α, MCP-1, MIP-1β, IP-10, IL-10, TGF-β2, and MMP-9 were quantified by commercial ELISA. Prespecified analyses compared each postoperative time point versus baseline in the control eye with multiplicity adjustment; operated-versus-control differences over time were evaluated in secondary analyses. The contralateral control eye showed a modest but measurable, predominantly subclinical inflammatory/chemotactic response after unilateral trabeculectomy, detectable primarily by aqueous humor biomarker analysis rather than by overt clinical signs, with multiplicity-adjusted elevations largely confined to an early postoperative interval (3 days–2 weeks) and an overall return toward baseline by 4 weeks. IL-6 and MCP-1 exhibited the most consistent early increases, whereas IP-10 showed a relatively delayed normalization trend. The operated eye demonstrated substantially stronger and more sustained postoperative activation, with the largest inter-eye separation occurring during the early window. Unilateral trabeculectomy was associated with a short-lived contralateral aqueous humor inflammatory/chemotactic shift that peaked within 3 days–2 weeks and largely resolved by approximately 4 weeks in rabbits. In this experimental setting, these changes appeared to be predominantly subclinical and biomarker-detectable rather than clinically overt. These descriptive findings suggest a putative early fellow-eye “fluctuation window” but do not provide evidence to guide clinical timing of second-eye surgery. Whether a similar temporal pattern exists in patients, and whether it has clinical relevance, requires prospective validation.
Purpose:Conjunctival scarring is a major cause of glaucoma filtration surgery (GFS) failure, necessitating effective antifibrotic strategies. This study investigated the role of engrailed-1 (EN1) in conjunctival fibrosis and evaluated the therapeutic potential of EN1-targeted biomaterials for antiscarring in post-GFS patients. Methods:Fibrotic models were developed using TGF-β2-induced human Tenon fibroblasts (HTFs) and a rat GFS model. EN1 was identified as a key therapeutic target using RNA interference, transcriptome sequencing, chromatin immunoprecipitation-qPCR, and dual-luciferase assays. Exosomes (Exos) loaded with EN1 small interfering RNA were encapsulated in a GelMA hydrogel to form the Gel-Exo-siEN1 composite material. Results:EN1 expression was significantly elevated in TGF-β2-stimulated HTFs and conjunctival scar tissue post GFS. Inhibition of EN1 reduced TGF-β2-induced proliferation and migration in HTFs and decreased fibrosis-related gene expression. These effects may be mediated through the Yes-related protein/transcriptional co-activator PDZ-binding motif and SMAD3 pathways. Assays confirmed that EN1 inhibition suppressed proliferation and migration and downregulated fibrosis markers like fibronectin, collagen I, and α-smooth muscle actin. Western blot analysis showed increased Yes-related protein/transcriptional co-activator PDZ-binding motif expression after TGF-β2 induction, which was reduced by verteporfin. Chromatin immunoprecipitation-PCR confirmed that SMAD3 binds to the EN1 promoter, regulating its expression. Exo analysis showed Exo-siEN1 maintained stability and effectively delivered siEN1, leading to significant EN1 knockdown and reduced fibrosis in rat Tenon's fibroblasts. Gel-Exo-siEN1 treatment significantly increased functional bleb area, reduced IOP, and decreased collagen deposition and inflammatory cell infiltration in the conjunctiva after GFS. Conclusions:Gel-Exo-siEN1 is a promising strategy for preventing postsurgical scarring and improving the outcomes of glaucoma surgery.
Minimally invasive glaucoma surgery (MIGS) presents substantial challenges due to its intricate procedures and high technical demands, necessitating robust surgical navigation systems. The development of these systems is highly dependent on the availability of precisely annotated datasets. Addressing this need, we have created the first multicenter, large-scale, fine-annotated surgical video dataset for MIGS. This dataset includes millions of frames, extensively annotated with both surgical instruments and anatomical structures. The annotations are organized into two primary tasks: Task I, which involves phase recognition to identify different stages of the surgery, and Task II, which focuses on semantic segmentation of surgical instruments and anatomical details. By providing a foundational resource for training computer vision models, our dataset aims to facilitate the development of advanced computer-assisted interventions that can improve the precision and safety of glaucoma surgeries.
Postoperative scarring and failure of surgically created drainage pathways limit durable glaucoma surgery. We developed a solid plate-type suprachoroidal space (SCS) implant based on hydroxyapatite-coated magnesium (HA-Mg) to provide temporary pathway support, an HA-modified material-tissue interface, and progressive biodegradation. TGF-β2-stimulated human iris pigment epithelial cells were used to assess material-associated effects on migration and fibrotic activation. In a paired-eye normotensive New Zealand White rabbit model, trabeculectomy, sham SCS surgery, titanium, uncoated magnesium, and HA-Mg groups were evaluated for 24 weeks using intraocular pressure (IOP) monitoring, ex vivo SCS angiography, micro-computed tomography, histology, α-smooth muscle actin (α-SMA) immunofluorescence, corneal endothelial assessment, aqueous humor pH, and systemic safety analyses. HA-Mg produced a sustained, stable IOP-lowering profile, whereas both Mg and HA-Mg showed greater net IOP reduction at Week 24 than the other surgically treated groups. HA-Mg showed broader posterior SCS contrast enhancement at Weeks 12 and 24. From Week 4 to Week 24, residual implant volume and surface area decreased by 93.6% and 86.3%, respectively, although residual material remained. Histology and α-SMA analysis were consistent with reduced fibrosis-associated interface remodeling, and Mg and HA-Mg extracts attenuated TGF-β2-induced migration and α-SMA expression. No evident ocular or systemic safety concerns were detected within 24 weeks. HA-Mg therefore supported medium-term preservation of the surgically created SCS outflow pathway while undergoing substantial but incomplete degradation; longer-term studies extending through and beyond complete implant resorption are required to determine whether pathway patency and safety are maintained thereafter. STATEMENT OF SIGNIFICANCE: Glaucoma drainage surgery remains limited by progressive fibrosis, foreign-body responses, and loss of long-term drainage pathway function. Although suprachoroidal space (SCS) approaches provide an alternative aqueous outflow route, maintaining pathway patency while minimizing the burden of permanent implants remains challenging. Here, we developed a biodegradable hydroxyapatite-coated magnesium (HA-Mg) drainage plate designed to provide temporary structural support and gradually degrade during tissue remodeling. The study integrates material characterization, medium-term in vivo evaluation, degradation tracking, fibrosis-associated remodeling assessment, and biosafety analysis in a rabbit model. Our findings support a biomaterial strategy that couples progressive biodegradation with preservation of SCS outflow-associated function, providing a potential framework for next-generation biodegradable implants in glaucoma surgery and other applications requiring temporary tissue-implant interfaces.
PURPOSE:To evaluate the 3-year efficacy and safety of phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma (PACG) with cataract. DESIGN:Multicenter, randomized controlled, open-label, non-inferiority trial. METHODS:Patients were randomized 1:1 to undergo either phacogoniotomy (65 eyes) or phacotrabeculectomy (59 eyes). Three years retention was 92.3% (60/65) and 83.1% (49/59) for each group, respectively. Primary outcome was 3-year intraocular pressure (IOP) reduction (noninferiority margin: 4 mmHg). Secondary outcomes included surgical success, complications, hypotensive medications used; additional outcomes were changes in visual acuity (BCVA), visual field (VF), and corneal endothelial cell density (ECD). RESULTS:At 3 years, phacogoniotomy reduced mean IOP from 40.2 (10.3) to 14.1 (2.4) mmHg (-26.1 [10.4] mmHg reduction); phacotrabeculectomy, from 39.7 (9.3) to 14.4 (2.5) mmHg (-25.3 [9.2] mmHg reduction). Adjusted between-group difference in IOP change was -0.37 mmHg (95% CI, -1.32-0.58 mmHg; P = 0.44), meeting noninferiority. Complete (78.3% vs 89.8%; P = 0.13) and qualified (90.0% vs 91.8%; P > 0.999) success rates were comparable. Hypotensive medications declined in both groups (phacogoniotomy: 2.1 [1.2] to 0.2 [0.6]; phacotrabeculectomy: 2.1 [1.3] to 0.0 [0.2]; P = 0.06 for 3-year difference). BCVA improvements (0.1 vs 0.0 logMAR; P = 0.49), VF stability (MD difference:1.42 dB, P = 0.26; PSD difference: 0.22 dB, P = 0.75), and ECD loss (difference: 2%; P = 0.53) were similar. No new complications occurred in extended follow-up. CONCLUSIONS:At 3 years, phacogoniotomy remained non-inferior to phacotrabeculectomy in IOP reduction for advanced PACG with cataract.
PURPOSE:To evaluate the visual preservation, safety, and surgical outcomes of phacogoniotomy (phacoemulsification combined with or without goniosynechialysis and goniotomy) in patients with end-stage glaucoma. METHODS:This multicenter retrospective study included 134 eyes of 128 patients (92 primary angle-closure glaucoma [PACG] and 42 primary open-angle glaucoma [POAG]) with end-stage glaucoma (defined as inability to perform perimetry or visual acuity ≤ 20/200). Patients underwent phacogoniotomy and were followed ≥ 12 months. Main outcomes included best-corrected visual acuity (BCVA), intraocular pressure (IOP), medication burden, and complications, with specific attention to the "wipe-out" phenomenon. RESULTS:At a mean follow-up of 19.2 ± 8.0 months, no cases of "wipe-out" (sudden, immediate, irreversible central vision loss) occurred. BCVA improved in 63.1% of eyes and remained stable in 30.3%. The mean IOP decreased significantly from 31.4 ± 9.7 mm Hg to 14.1 ± 3.3 mm Hg (P < 0.001) and mean number of medications dropped from 2.2 ± 1.4-0.6 ± 1.0 (P < 0.001). Complete success rate was 67.9% overall, with 76.1% for PACG and 50.0% for POAG (P = 0.005). Qualified success rate was 97.0% overall, with 96.7% for PACG and 97.6% for POAG (P = 0.695). The most common complications were transient hyphema (11.2%) and IOP spike (3.7%). CONCLUSIONS:In end-stage glaucoma, phacogoniotomy is a safe and effective procedure that significantly lowers IOP while preserving or improving vision in > 90% of cases. The procedure may reduce the risk of "wipe-out" associated with traditional filtration surgery and appears particularly effective in eyes with angle-closure mechanisms.
PURPOSE:To evaluate the impact of prolonged use of topical glaucoma medications on the surgical outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in juvenile open-angle glaucoma (JOAG). PATIENTS AND METHODS:This multicenter retrospective study included 100 eyes of 77 JOAG patients who underwent GATT with at least 12 months of follow-up. Patients were categorized into the short-duration (≤ 1.5 years) and long-duration (> 1.5 years) groups. Intraocular pressure (IOP), glaucoma medications, and complications were recorded at baseline and the final visit. Success was defined as a postoperative IOP ≤ 21 mmHg (criterion A), ≤ 18 mmHg (criterion B), or ≤ 15 mmHg (criterion C). Complete and qualified successes were defined as meeting these criteria without and with medications, respectively. RESULTS:The mean age of the participants was 23.2 ± 8.6 years with a mean follow-up of 14.2 ± 4.1 months. Qualified and complete success rates for the short-duration and long-duration groups were 98.0 % and 92.0 % (P = 0.369), 80.0 % and 66.0 % (P = 0.322) for criterion A; 92.0 %, and 68.0 % (P = 0.006), 78.0 % and 50.0 % (P = 0.021) for criterion B; 66.0 % and 40.0 % (P = 0.013), 58.0 % and 30.0 % (P = 0.015) for criterion C. The short-duration group had a significantly lower final IOP than the long-duration group (P = 0.011). No significant differences were observed in final medication and complications. CONCLUSIONS:Prolonged use of topical glaucoma medications may reduce the efficacy of GATT in achieving lower IOP in JOAG. Early surgical intervention may contribute to better postoperative outcomes.
PRÉCIS:Phacogoniotomy, a combination of phacoemulsification and intraocular lens implantation (PEI) and 120-degree goniotomy (GT), was an effective and safe surgical treatment for medically controlled or uncontrolled primary open angle glaucoma (POAG) with cataract. PURPOSE:To evaluate the efficacy and safety of PEI combined with 120-degree GT in the treatment of medically controlled or uncontrolled POAG with cataract. METHODS:Multicenter observational study conducted in 9 ophthalmic institutes/general hospitals in China. Patients with medically controlled [baseline intraocular pressure (IOP) ≤21 mmHg] or uncontrolled (baseline IOP > 21 mmHg) POAG with clinically significant cataract were included, who were followed up with at least 12 months. The IOP, topical hypotensive medication, surgery complications, visual acuity, surgery success were recorded and compared between groups at baseline and the final visit. Complete surgical success was defined as postoperative IOP of 5-18 mmHg without additional topical medications, vision-threatening complications or reoperation for glaucoma. Qualified success is same as complete success except allowing use of ocular hypotensive medications. RESULTS:One hundred participants with 132 eyes were included with a mean follow-up time of 17.5±5.2 months ( range:12-32) postoperatively. In general, the mean IOP reduced from 21.2±7.4 mmHg at baseline to 14.7±2.9 mmHg postoperatively ( P <0.05), with an average reduction of 6.4±7.9 mmHg (23.5±25.6%). The mean number of hypotensive medications declined from 1.6±1.2 to 0.3±0.6, with a mean reduction of 1.4±1.2. One hundred eight out of 132 (81.8%) eyes achieved complete success and 118 (89.4%) achieved qualified success of surgery, respectively. The chief complications involved hyphema (15.2%), corneal edema (19.7%), IOP spike (8.3%), or hypotony (1.5%). In subgroup analysis of medically controlled versus medically uncontrolled pariticpants, difference was found neither in IOP at final visit (14.5±0.3 vs. 15.1±0.4 mmHg; P =0.28), medication (1.8±1.1 vs. 1.4±1.3; P =0.54), and complete (85.3% vs. 77.2%; P =0.23) or qualified success rate (95.0% vs. 86.0%; P =0.27), nor in any kind of surgery complications (all P s>0.05), respectively. CONCLUSION:POAG with cataract could be effectively treated by phacogoniotomy, regardless of medically controlled or medically uncontrolled status at baseline.
Importance:The safety and effectiveness of combining surgical peripheral iridectomy (SPI) with goniosynechialysis (GSL) and goniotomy (GT) vs trabeculectomy for intraocular pressure (IOP) reduction remains unknown. Objective:To investigate the safety and effectiveness at 1 year of SPI + GSL + GT vs trabeculectomy in advanced primary angle-closure glaucoma (PACG) without cataract. Design, Setting, and Participants:This noninferiority randomized clinical trial was conducted at 8 tertiary eye centers in China. A total of 88 Chinese patients (88 eyes) with advanced PACG without cataract were enrolled from January 2022 to July 2023. Data were analyzed from August 2024 to September 2024. Mean (SD) patient age was 60.3 (7.3) years, and 52 patients (59.1%) were female. Forty-three patients were randomized to SPI + GSL + GT and 45 were randomized to trabeculectomy; 86 patients (97.7%) completed the 12-month follow-up. Interventions:Participants were randomized 1:1 to receive SPI + GSL + GT or trabeculectomy. Main Outcomes and Measures:The primary outcome was IOP at 12 months (noninferior margin: 4 mm Hg). Secondary outcomes included surgical success (IOP: 5-18 mm Hg, ≥20% reduction from baseline, with or without antiglaucoma medications); postoperative complications and interventions, including bleb massage, suture lysis, or releasable sutures; and number of antiglaucomatous medications prescribed. Results:At 12 months, the SPI + GSL + GT group had a mean (SD) IOP of 15.6 (4.0) mm Hg vs 14.9 (4.2) mm Hg in the trabeculectomy group (difference, 0.5 mm Hg; 95% CI, -1.2 to 2.2; P = .55), which was within the 4-mm Hg noninferiority margin. Qualified success rates were 38 of 43 participants (88.4%) for SPI + GSL + GT and 42 of 45 participants (93.3%) for trabeculectomy (difference, -5.0%; 95% CI, -19.6% to 8.5%; P = .48). However, complete success rates were lower in the SPI + GSL + GT group (26 participants [60.5%]) vs the trabeculectomy group (37 participants [82.2%]; difference, -21.8%; 95% CI, -40.2% to -2.4%; P = .03). Postoperative complications were present for 8 participants (18.6%) in the SPI + GSL + GT group vs 9 participants (20.0%) in the trabeculectomy group (difference, -1.4%; 95% CI, -17.9% to 15.1%; P = .71). Postoperative interventions were lower in the SPI + GSL + GT group (3 participants [7.0%] vs 25 participants [55.6%]; difference, 48.6%; 95% CI, 32.2%-65.0%; P < .001). Median (IQR) numbers of medications used decreased from 2 (0-3) to 0 (0-1) in the SPI + GSL + GT group and from 2 (2-3) to 0 (0-0) in the trabeculectomy group (difference, -0.81; 95% CI, -1.36 to -0.26; P = .004). Conclusions and Relevance:In this randomized clinical trial among patients with advanced PACG without cataract, SPI + GSL + GT demonstrated noninferiority (4-mm Hg margin) to trabeculectomy for IOP at 12 months, with fewer interventions (including bleb massage, suture lysis, or releasable sutures) but no difference in postoperative medication use. This suggests SPI + GSL + GT as a potential alternative to trabeculectomy for similar cases, pending validation in larger sample sizes with smaller noninferiority margins. Trial Registration:ClinicalTrials.gov Identifier: NCT05163951.
Importance:Intraocular pressure (IOP) reduction with phacogoniotomy (phacoemulsification plus goniosynechialysis plus goniotomy) was not less than that of phacotrabeculectomy for advanced primary angle-closure glaucoma (PACG) with cataract at 1-year follow-up, but longer-term outcomes are needed. Objective:To investigate if phacogoniotomy is noninferior to phacotrabeculectomy for advanced PACG with cataract at 2 years. Design, Setting, and Participants:This multicenter, noninferiority, randomized clinical trial took place in 7 ophthalmology centers in China. The trial started May 31, 2021, and 2-year follow-up ended May 31, 2024. Included in this analysis were patients with advanced PACG and cataract. Study data were analyzed from September 2024 to January 2025. Interventions:Random assignment (1:1) to phacogoniotomy or phacotrabeculectomy. Main Outcomes and Measures:The primary outcome measure was reduction in IOP from baseline to the 2-year visit with a noninferiority margin of 4 mm Hg. Results:A total of 124 participants (124 eyes) were randomized (mean [SD] age, 66.4 [8.6] years; 67 female [54.0%]), 65 (52.4%) to the phacogoniotomy group and 59 (47.6%) to the phacotrabeculectomy group. A total of 59 patients (90.7%) in the phacogoniotomy group and 52 patients (88.1%) in the phacotrabeculectomy group completed 2-year visits. All participants were Chinese. Mean (SD) IOP reduction was -25.6 (10.2) mm Hg and -24.7 (9.4) mm Hg in the phacogoniotomy and phacotrabeculectomy groups, respectively, and the upper boundary of the CI for difference in change between groups was lower than the 4-mm Hg noninferiority margin (mean difference, -0.5 mm Hg; 97.5% CI, -1.7 mm Hg to 0.8 mm Hg; P = .42). The mean difference for complete success for phacogoniotomy vs phacotrabeculectomy was -6.7% (95% CI, -21.4% to 8.8%; P = .47) and for qualified success was 1.4% (95% CI, -11.0% to 14.3%, P = .30). Median (IQR) number of antiglaucomatous medication was 0 (0) vs 0 (0; Hodges-Lehmann estimate of location shift, 0; 95% CI, 0; P =.12) with phacogoniotomy vs phacotrabeculectomy, respectively (mean difference, 0.13; 95% CI, -0.36 to 0.63; P = .60). Conclusions and Relevance:Mean IOP reduction with phacogoniotomy was noninferior to phacotrabeculectomy for advanced PACG and cataract at 2-year follow-up with no differences detected in complete or qualified success or mean number of antiglaucomatous medications. These findings support phacogoniotomy as an alternative to phacotrabeculectomy for patients with advanced PACG and cataract. Trial registration:ClinicalTrials.gov Identifier: NCT04878458.
High-intensity focused ultrasound cycloplasty (UCP) can effectively reduce intraocular pressure in glaucoma patients. This work aimed to analyze the efficacy, safety, and mechanism of UCP in treating acute angle-closure glaucoma. We collected and retrospectively analyzed the preoperative and postoperative clinical data of 16 cases (16 eyes) with acute angle-closure glaucoma, including the number of sectors activated, intraocular pressure (IOP), central anterior chamber depth (ACD), lens zonule length (LZL), ciliary muscle thickness (CMT), and trabecular-ciliary process angle (TCA). Of the 16 eyes, one received a single UCP procedure with 8 sectors, and the others with 10 sectors. The mean IOP at follow-up time points after UCP was significantly lower than before UCP. The mean ACD at follow-up time points after UCP was significantly higher than before UCP. The mean LZL in the superior, inferior, nasal, and temporal quadrants on postoperative day 1, week 1, and month 1 was significantly shorter than that before UCP. The mean CMT in the superior, inferior, and nasal quadrants on postoperative day 1 and in the superior and inferior quadrants on postoperative week 1 were significantly larger than those before UCP. The mean TCA in the temporal quadrant on postoperative month 3 was significantly smaller than that before UCP. In conclusion, UCP is safe and effective in treating acute angle-closure glaucoma. The special mechanism of lowering IOP after UCP may be attributed to the increased depth of the central anterior chamber and the reopening of some non-adhesive closed angles.
Given the alarmingly increasing rates of glaucoma worldwide and the lack of satisfactory treatments, there is a dire need to explore more feasible treatment options. Magnesium (Mg) is an essential element in maintaining the functional and structural integrity of vital ocular tissues, but Mg and its alloys are rarely mentioned in ophthalmic applications. Our previous research found that hydroxyapatite-coated Mg (Mg@HA) shows the best biocompatibility and bioactivity, and exhibits the effect of inhibiting fibrosis after filtration surgery in the rabbit model, which is expected to be a promising material for glaucoma drainage device. In this study, we further demonstrated the anti-fibrosis effect of Mg@HA from the molecular signal level and the efficacy of implantation in the rabbit filtration surgery model. In vitro experiments showed the surface modification of Mg affects the adhesion behavior and the reorganization of cytoskeleton of Human Western blot analysis and immunofluorescence found that Mg@HA regulates the adhesion and motility of human Tenon's capsule fibroblasts mainly by down-regulating the phosphorylation of Smad2 and Smad3 in the canonical transforming growth factor-beta (TGF - β) signaling pathway. By observing and recording the condition of filtering blebs and intraocular pressure after surgery, the effectiveness of Mg@HA applied in the rabbit filtration surgery model was further evaluated. In conclusion, the application of hydroxyapatite-coated Mg in the eye has good biocompatibility and has the potential to resist postoperative glaucoma filtration fibrosis, which may be mediated by the regulation of the TGFβ/Smad signaling pathway.
To report the 2-year effective and safety profile of integrated phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL) and 120° goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) and cataracts. Multicentre prospective study. 201 eyes of 196 patients who received combined PEI+GSL+ GT were assessed at baseline and re-evaluated at days 1, 7, and at 1, 3, 6, 12 and 24 months postsurgery. The intraocular pressure (IOP), the number of topical hypotensive medications, surgical complications and achievements of surgery success were also evaluated. All participants were followed up for a 2-year period. The average IOP declined from 33.0±10.7 mm Hg to 13.6±2.9 mm Hg, and the number of topical hypotensive medication decreased from an average of 2.4 types to 0.4 at month 24. For the safety profile, the major complications were hyphema (n=14, 7.0%), IOP spike (n=9, 4.9%) and transit corneal oedema (n=23, 11.4%). The complete success was achieved in 72.6% of the eyes (146 out of 201), and the qualified success rate was 91.5% (184 out of 201). Only one eye required tube shunt surgery while no one developed severe vision-threatening complications. The best-corrected visual acuity increased from 0.80±1.08 to 0.54±0.78 LogMAR. PEI+GSL+GT is shown to be effective and safe in treating advanced PACG with cataract over a 2-year follow-up period. The combined surgery may be considered as an alternative for patients with advanced PACG.
PRÉCIS:240-degree and 360-degree goniotomy (GT) demonstrated similar efficacy in intraocular pressure (IOP) reduction, both outperforming 120-degree GT in patients with juvenile open angle glaucoma (JOAG) at postoperative 6-month follow-up. OBJECTIVE:To compare the surgical efficacy and safety of 120-degree, 240-degree, and 360-degree GT for patients with JOAG. PATIENTS AND METHODS:This multicenter retrospective study included 102 eyes of 102 patients with JOAG, who underwent GT with a follow-up of at least 6 months. Patients were categorized into 3 groups: (1) 120-degree GT, (2) 240-degree GT, and (3) 360-degree GT. IOP, glaucoma medications, and complications were recorded at baseline and the final visit. Complete success and qualified success were defined as a postoperative IOP ≤21 mm Hg without and with medications, respectively. RESULTS:Mean age of the participants was 24.4 ± 7.9 years. After a mean follow-up of 8.1 ± 2.7 months, complete success rates were similar between the 240-degree GT (45.2%) and the 360-degree GT (63.2%; P = 0.135), and both were superior to 120-degree GT (18.2%; P < 0.05). Qualified success rates among patients in the 120-degree, 240-degree, and 360-degree GT groups were 93.9%, 96.8%, and 100%, respectively, and showed no statistically significant difference ( P = 0.292). 360-degree GT required fewer medications than 240-degree GT and 120-degree GT ( P < 0.05), with no significant difference in medications between 120-degree GT and 240-degree GT ( P > 0.05). Hyphema was the most common postoperative complication, with a significantly higher incidence in the 360-degree GT (68.4%) compared with the 240-degree GT (41.9%) and 120-degree GT (33.3%; P < 0.05). CONCLUSIONS:240-degree and 360-degree GT showed similar efficacy in IOP reduction and were superior to 120-degree GT. More extensive GT may provide better outcomes in JOAG.
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