Impact of Peripheral Anterior Synechiae on the Outcome of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Primary Angle Closure Glaucoma and Cataract: A Multicenter Observational Study.

PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae. PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

One-Year Results of a Multicenter Study: Intraocular Pressure-Lowering Effect of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Cases of Advanced Primary Angle-Closure Glaucoma With Cataract.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of the combination of phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes of advanced primary angle-closure glaucoma (PACG) with cataract. DESIGN: Multicenter observational study. METHODS: We enrolled 83 eyes of 83 patients with advanced PACG who received combined PEI+GSL+GT at 8 ophthalmic institutes. Each patient was assessed before treatment and at 1, 7 days, 1, 3, 6, and 12 months postsurgery. The criteria for complete success were IOP within 6 to 18 mm Hg and at least 20% of reduction in IOP from baseline without ocular hypotensive medications or reoperation. The definition of qualified success was similar to that of complete success, except for the need for ocular hypotensive medications. The potential prognostic factors for surgical success were investigated using a multivariate logistic model. RESULTS: All participants completed 1 year of follow-up. Complete and qualified success were achieved in 74 (89.1%) and 79 (95.2%) of 83 eyes, respectively. The mean preoperative and postsurgical IOPs were 27.4±7.3 and 14.2±2.6 mm Hg, respectively. Participants used an average of 2.0 and 0.3 types of ocular hypotensive medications before and after surgery, respectively. The chief complications included hyphema (n=9), IOP spike (n=9), and corneal edema (n=8). None of the eyes required reoperation or developed vision-threatening complications. Multivariate analysis showed that older age was associated with a higher probability of complete success (odds ratio=1.13; 95% CI: 1.02-1.25; P=0.020). CONCLUSIONS: The 1-year results of combination of PEI+GSL+GT in treating advanced PACG cases with cataract appear to be safe and effective. Further large-scale multination and multicenter studies are warranted.

Efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre non-inferiority randomised controlled trial (PVP Study).

INTRODUCTION: Primary angle-closure glaucoma (PACG) has a high prevalence and blinding rate across Asia. The first-line treatment of PACG is surgery, and phacotrabeculectomy remains the mainstream surgery for advanced PACG. However, it may cause vision-threatening complications with long learning curve. Minimally invasive glaucoma surgery has been gradually used in PACG combined with cataract surgery and achieved efficacy without excessive injury, of which goniotomy is the most commonly performed. Therefore, this study aimed to conduct a multicentre, non-inferiority randomised controlled clinical trial to compare the efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced PACG. METHODS AND ANALYSIS: This is a non-inferiority multicentre randomised controlled trial and will be conducted at eight ophthalmic departments and institutes in China. 124 patients with advanced PACG will be enrolled and randomised to undergo phacotrabeculectomy or phacogoniotomy. Comprehensive ophthalmic examinations will be performed before and after the surgery. The primary outcome is the change of intraocular pressure at 12 months after surgery compared with the baseline intraocular pressure. An extended follow-up period of 36 months will be required. Cumulative success rate of surgery, intraoperative and postoperative complications, and number of anti-glaucomatous medications will also be compared between the groups as secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethical committee of Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ090) and all subcentres. All the participants will be required to provide written informed consent. The results will be disseminated through scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04878458.

3-Methyladenine Alleviates Experimental Subretinal Fibrosis by Inhibiting Macrophages and M2 Polarization Through the PI3K/Akt Pathway.

Purpose: To explore the effects of 3-methyladenine (3-MA), a selective inhibitor of phosphatidylinositol-3-kinase (PI3K), on experimental subretinal fibrosis (SRF) in mice. Methods: The SRF mouse model was established by 532 nm laser photocoagulation at each fundus of mice on day 0. 3-MA was administered every 2 days from day 0 to 35. Immunofluorescence of choroidal flat mounts was performed to evaluate the size of SRF area, local macrophages, and polarization, respectively. Besides, Western blot analysis was carried out to assess the expression levels of macrophage polarization-related genes, Arg-1, Ym-1, and transforming growth factor-ß2 (TGF-ß2). Co-culture and migration experiments were used to demonstrate the inhibitory effect of 3-MA on fibroblasts. The gene knockout and Western blot analysis were used to explore the signal pathways related to macrophage polarization. Results: Compared with the control group, the 3-MA-treated group showed significantly less size of SRF area. 3-MA treatment reduced both circulating and local macrophages, and counteracted M2 polarization. Moreover, 3-MA inhibited fibroblast recruitment. Mechanistically, we proved that 3-MA inhibits macrophage M2 polarization by suppressing PI3K/Akt signal pathway rather than the PI3K-autophagy-related signal pathway. Conclusions: 3-MA exerts antifibrotic effects on experimental SRF by targeting circulating and local macrophages and M2 polarization, through PI3K/Akt signal pathway. These results support the potential use of 3-MA as a new therapeutic modality for SRF associated with neovascular age-related macular degeneration.

Evaluation of Retinal Pigment Epithelium and Choroidal Neovascularization in Rats Using Laser-Scanning Optical-Resolution Photoacoustic Microscopy.

PURPOSE: To demonstrate the value of the laser-scanning optical-resolution (LSOR)-photoacoustic (PA) microscopy (PAM) system and the conventional multimodal imaging techniques in the evaluation of laser-induced retinal injury and choroidal neovascularization (CNV) in rats. METHODS: Different degrees of retinal injury were induced using laser photocoagulation. We compared the LSOR-PAM system with conventional imaging techniques in evaluating retinal injury with or without CNV. Six additional rats, treated with an anti-VEGF antibody or immunoglobulin G immediately after photocoagulation, were imaged 7 and 14 days after injection, and CNV lesion areas were compared. RESULTS: In the retinal injury model, fundus autofluorescence showed well-defined hyperreflection, while the lesion displayed abundant PA signals demonstrating nonuniform melanin distribution in retinal pigment epithelium (RPE). RPE was detected with higher contrast in the PAM B-scan image than optical coherence tomography (OCT). Additionally, the CNV lesion was present with multiple PA signal intensities which distinctly characterized the location and area of CNV as found in fundus fluorescein angiography. Furthermore, the decreased PA signals extending from the CNV lesion were similar to those of the vascular bud in ex vivo imaging, which was invisible in other in vivo images. When treated with anti-VEGF agents, statistically significant differences can be demonstrated by PAM similar to other modalities. CONCLUSIONS: LSOR-PAM can detect the melanin distribution of RPE in laser-induced retinal injury and CNV in rats. PAM imaging provides a potential new tool to evaluate the vitality and functionality of RPE in vivo as well as to monitor the development and treatment of CNV.

Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina.

VEGF is a critical driver of ocular neovascularization under disease conditions. Current therapeutic strategies rely on intraocular delivery of VEGF-antagonizing reagents, which results in sustained suppression of pathogenic vascularization. Although significant advancement has been achieved in VEGF antagonism, substantial adverse effects have been reported in retrospective clinical studies. To study mechanisms for VEGF antagonism-associated adverse effects in visual system, we intravitreally delivered recombinant adeno-associated virus-mediated expression of soluble Fms-related tyrosine kinase-1 (rAAV.sFLT-1), the extracellular domain of VEGF receptor, and analyzed the morphology and functions of retinal tissue. Here, we confirmed that intraocular VEGF antagonism induced retinal degeneration and gliosis. The functional deficit in retinal response to visual stimulation was also demonstrated in rAAV.sFLT-1-treated eyes by electroretinogram. Moreover, high-throughput RNA sequencing analysis suggests that VEGF antagonism activates retinal degeneration, inflammation, and other adverse effects. Taken together, our findings have shed light on pathogenic mechanisms for VEGF antagonism-associated adverse effects and potential therapeutic targets.-Xiao, M., Liu, Y., Wang, L., Liang, J., Wang, T., Zhai, Y., Wang, Y., Liu, S., Liu, W., Luo, X., Wang, F., Sun, X. Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina.

POSTERIOR PRECORTICAL VITREOUS POCKETS IN HIGH MYOPIA OBSERVED BY ENHANCED VITREOUS IMAGING OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To observe the vitreous in highly myopic eyes with posterior precortical vitreous pockets (PPVPs) using enhanced vitreous imaging of spectral domain optical coherence tomography. METHODS: Fifty-two highly myopic eyes with PPVPs of 36 patients were included in this study. All subjects underwent enhanced vitreous imaging optical coherence tomography. The size of PPVPs was measured, and the frequency of imaging features was recorded. RESULTS: Nine imaging features of the vitreous in highly myopic eyes with PPVPs were found. The average age of subjects was 38.1 ± 10.8 years. The mean height of PPVPs was 1,177 ± 704 µm, and the mean width was 7,440 ± 755 µm. Hyperreflective line and the interlayer were observed in 30 (57.7%) eyes. Hyperreflective dots were found in 37 (71.2%) eyes. More central vitreous space was more frequently detected in younger patients. Prevascular vitreous fissure was detected in 7 (13.5%) eyes. W-shaped cavity, identified as an empty space with a smooth W-shaped edge, was demonstrated to be the fusion of Cloquet's canal and the extension of PPVPs. Perpendicular hyperreflective parallel strands were detected in 3 (5.8%) eyes. Hyperreflective network was observed in 10 (19.2%) eyes. Hyperreflective parapapillary tubercle was found in 7 (13.5%) eyes. CONCLUSION: Nine imaging features of the vitreous in highly myopic eyes with PPVPs were visualized by enhanced vitreous imaging optical coherence tomography.

OBSERVATION OF VITREOUS FEATURES USING ENHANCED VITREOUS IMAGING OPTICAL COHERENCE TOMOGRAPHY IN HIGHLY MYOPIC RETINOSCHISIS.

PURPOSE: To observe features of the posterior vitreous and vitreoretinal interface in highly myopic eyes with retinoschisis using enhanced vitreous imaging optical coherence tomography. METHODS: Comprehensive ophthalmologic examination and enhanced vitreous imaging optical coherence tomography were performed in 77 eyes of 63 patients with highly myopic retinoschisis. Two different modes of spectral domain optical coherence tomography were employed to estimate retinoschisis and the posterior vitreous features in optical coherence tomography images, respectively. The types and distribution of vitreoretinal interface abnormalities were also analyzed. RESULTS: Complete posterior vitreous detachment (PVD) was identified in 55 eyes (71.4%) with a Weiss ring. Residual cortex was found in 39 eyes (70.9%) with complete PVD. Vitreoretinal interface changes, including vitreoretinal adhesion and epiretinal membrane (ERM), most frequently appeared in the macular area (47.3%), followed by the inferior arched vessels region (34.5%). In partial PVD eyes, vitreoretinal traction, vitreoretinal adhesion, and epiretinal membrane tended to be observed in the inferior and superior arched vessels regions (54.5 and 40.9%, respectively). Among all types of vitreoretinal interface abnormalities, epiretinal membrane comprised the largest proportion (46.8%) despite the status of PVD. The presence of inner layers of retinoschisis connoted a relatively high possibility of vitreoretinal interface abnormalities occurring. CONCLUSION: Enhanced vitreous imaging optical coherence tomography reveals a high prevalence of vitreoretinal interface abnormalities in highly myopic eyes with retinoschisis. Vitreous cortex tends to remain on the macular area in eyes with complete PVD. Our findings may lead to better guidance for the surgical treatment of highly myopic retinoschisis.

Paravascular abnormalities observed by spectral domain optical coherence tomography are risk factors for retinoschisis in eyes with high myopia.

PURPOSE: To investigate the retinal features and distribution of paravascular abnormalities (PVAs) and their relationship with retinoschisis in eyes with high myopia. METHODS: One hundred and fifty-two eyes of 88 patients with high myopia [refractive error greater than -6 dioptres (D) or axial length (AL) ≥26.5 mm] who had undergone comprehensive ophthalmic examinations were evaluated in this cross-sectional study. Multiple optical coherence tomography (OCT) scans were performed to study the microstructural alterations adjacent to the retinal vascular arcades and the entire macular area. The presence and distribution patterns of various PVAs, retinoschisis and the association between these parameters were analysed. RESULTS: Of the 152 highly myopic eyes, PVAs were detected by OCT in 126 eyes (82.9%), including paravascular microfolds in all 126 eyes, paravascular cysts in 109 eyes (71.7%) and paravascular lamellar holes in 44 eyes (28.9%). All three types of PVAs were observed more frequently along the temporal vascular arcades than along the nasal vascular arcades (p < 0.005). Seventy-eight eyes (51.3%) were identified with retinoschisis at retinal vascular arcades, most frequently in the inner plexiform layer (IPL) and along temporal arcades. Eyes with all three types of PVAs (microfolds, cysts and lamellar holes) had the highest incidence of retinoschisis at vascular arcades (p < 0.001). Multivariate analysis indicated that age, the AL, presence of paravascular microfolds and cysts, and simultaneously existence of all three types of PVAs were associated with an increased risk for retinoschisis at vascular arcades. Macular retinoschisis was detected in 25 eyes (19.8%) and presented with splitting of the outer retina in all cases. All seven eyes with entire macular area retinoschisis (S4 grade) were accompanied by retinoschisis at vascular arcades within multiple layers, including outer retinoschisis, IPL schisis and inner limiting membrane (ILM) detachment. CONCLUSION: Our findings indicated that all three types of PVAs and different types of retinoschisis were most frequently observed along the temporal vascular arcades. Eyes with paravascular microfolds and cysts, and those with all three paravascular lesions may in risk of developing retinoschisis at vascular arcades.

Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice.

PURPOSE: The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice. METHODS: Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model. RESULTS: Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment. CONCLUSIONS: Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.