Yong Jie Qin

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are persistent environmental contaminants with potential adverse effects on human health, but their involvement in age-related macular degeneration (AMD) remains poorly understood. Here, we integrated transcriptomics, network toxicology, machine learning, Mendelian randomization (MR), gut microbiome analysis, molecular docking, and molecular dynamics simulations to investigate potential molecular targets linking PFOA/PFOS exposure to AMD. A total of 97 potential PFOA/PFOS-AMD targets were identified, and integrative machine learning analysis prioritized SLC1A4, ADAM17, EGFR, and MAPK10 as core genes. MR analysis suggested associations between genetically predicted SLC1A4 and ADAM17 expression and AMD, while molecular docking and molecular dynamics simulations suggested potential interactions between PFOA/PFOS and these candidate targets. Functional analyses implicated inflammatory responses, oxidative stress, and amino acid metabolic dysregulation. GutMGene analysis identified gut bacteria and microbial metabolites potentially linked to inflammatory genes. Collectively, these findings prioritize SLC1A4 and ADAM17 as candidate targets and provide a hypothesis-generating framework for experimental studies of the possible ocular effects of PFOA/PFOS.

Purpose: To evaluate the long‐term efficacy of phacoemulsification combined with trabeculectomy (Phaco‐Trab) for advanced chronic primary angle‐closure glaucoma (PACG) with cataract. Methods: Patients with advanced chronic PACG coexisting with cataracts who underwent Phaco‐Trab were enrolled. The morphologic structures of filtering blebs, including characteristics under slit‐lamp examination, anterior segment optical coherence tomography (AS‐OCT), and in vivo confocal microscopy (IVCM), were used to evaluate the filtering function. Results: A total of 30 eyes from 27 patients were enrolled. The mean preoperative intraocular pressure (IOP) of 19.98 ± 6.48 mmHg significantly decreased to 13.73 ± 2.35 mmHg at year 3 ( p < 0.0001). A statistically significant decrease in postoperative IOP‐lowering medications was observed, but the number of drugs used increased annually (0.50 ± 0.82 at year 1, 1.00 ± 0.98 at year 2, and 1.47 ± 0.97 at year 3, p < 0.0001). Following Phaco‐Trab, a high surgical qualified success rate was maintained over 3 years (93.3% at year 1, 90.0% at year 2, and 80.0% at year 3, p = 0.117). However, the complete success rate significantly decreased each year (70.0% at year 1, 36.7% at year 2, and 20.0% at year 3, p < 0.0001), along with an increase in the rate of failure filtering blebs, reaching 46.7%, 83.3%, and 90.0% at each time point ( p < 0.0001). Overall, 46.7% (14/30) of participants developed complications and required postoperative procedures after Phaco‐Trab, which were mainly induced by the trabeculectomy procedure. Conclusions: Phaco‐Trab can significantly lower IOP and reduce the use of IOP‐lowering medications for advanced chronic PACG with cataracts, but it is associated with a higher rate of complications and a higher failure rate of the filtering bleb.

Excessive uric acid (UA) is associated with age-related cataract. A previous study showed that a high UA level in the aqueous humor stimulated the senescence of lens epithelial cells (LECs), leading to cataract progression. To better understand the underlying mechanisms, we investigated UA-driven senescence in human lens tissue samples obtained during surgery, rat lens organ cultures, and in vivo experiments, using senescence-associated β-galactosidase (SA-β-gal) staining, electronic microscopy, Western blotting, and histological analyses. Initially, we identified markedly higher expressions of NLRP3 and caspase-1 in the lens capsules of hyper-uricemic patients compared to normo-uricemic patients. This increase was accompanied by a significant rise in the SA-β-gal positive rate. We next built a cataract model in which rat lenses in an organ culture system were treated with an increasing dosage of UA. Notably, opacification was apparent in the lenses treated with 800 μM of UA starting on the fifth day. Mechanistically, UA treatment not only significantly induced the expression of NLRP3, caspase-1, and IL-1β, but also upregulated the levels of SA-β-gal and the senescence regulators p53 and p21. These effects were fully reversed, and lens opacification was ameliorated by the addition of MCC950, a selective NLRP3 antagonist. Moreover, an in vivo model showed that intravitreal UA injection rapidly induced cataract phenotypes within 21 days, an effect significantly mitigated by co-injection with MCC950. Together, our findings suggest that targeting the UA-induced NLRP3 inflammasome with MCC950 could be a promising strategy for preventing cataract formation associated with inflammageing.

Background: To compare the efficacy of Ex-PRESS implantation versus trabeculectomy combined with phacoemulsification. Methods: A retrospective 12-month study on patients with coincident primary open-angle glaucoma (POAG) and cataract. The patients underwent combined phacoemulsification and Ex-PRESS implant (Phaco-ExPRESS, n = 35) or phacotrabeculectomy (Phaco-Trab, n = 35). The morphological structures of the filtering bleb were examined by slit-lamp, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). Complete success was defined as postoperative intraocular pressure (IOP) < 18 mmHg without the use of anti-glaucoma medication. Qualified success was defined as postoperative IOP < 18 mmHg with or without anti-glaucoma medications. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, and 12 months. Results: No significant difference in the variables such as age, IOP and perimetry was found between the groups of Phaco-ExPRESS and Phaco-Trab. At the one-year postoperative visit for filtering blebs, Phaco-ExPRESS increased the mean area of epithelial microcysts significantly from 0.10 ± 0.05 to 0.20 ± 0.09 μm² per μm², while Phaco-Trab decreased the mean area significantly from 0.08 ± 0.04 to 0.04 ± 0.06 μm² per μm². Notably, the hyperreflective dots detected by IVCM decreased by 84.9% in Phaco-ExPRESS but increased by 36.3% in Phaco-Trab. The hyperreflective dots were further identified as neutrophil- and monocyte-like cells. The number of these cells were negatively correlated with the microcysts area (r = − 0.7, P < 0.01) but positively associated with the grade of connective tissue (r = 0.5, P < 0.01). By creating different microstructural changes in the filtering blebs, Phaco-ExPRESS produced a higher complete success rate (84.9% vs. 41.2%, P < 0.01) and significant decrease in the number of anti-glaucoma medications (P < 0.01) when compared with those in Phaco-Trab. However, the qualified success showed no significant difference between the two groups (100.0% vs. 91.2%, P = 0.24). Conclusions: At the one-year follow-up, Phaco-ExPRESS generated better filtering bleb with larger area of microcysts, looser connective tissues, and less inflammation than that of Phaco-Trab, providing adequate IOP control and less IOP-lowering medications. These findings indicate that Phaco-ExPRESS could be more preferred than Phaco-Trab for the treatment of patients with coincident POAG and cataract.

Purpose: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. Methods: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. Results: A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61–18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73–1.23]) or serum UA (0.90 [95% CI, 0.66–1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12–1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99–1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME. Conclusion: Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

Purpose . To evaluate the clinical outcome of the three‐random‐point (TRP) marking method for toric intraocular lens (IOL) alignment using the iTrace aberrometer (Tracey Technologies Corp., Houston, TX). Setting . Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People’s Hospital, Guangzhou, China. Design . Prospective, randomized comparative trial. Method . Thirty eyes of 30 patients undergoing cataract surgery with coexisting corneal astigmatism of over 1.0 D were included in this study. All patients were prospectively randomized into the TRP marking group or slit‐lamp horizontal meridian (SHM) marking group. TRP marking involved marking three points randomly in the corneal limbus of the patients and accurately marking the horizontal meridian was not required. The follow‐up duration was 3 months after cataract surgery. Results . Fifteen eyes of 15 patients were in the TRP marking group and 15 eyes of 15 patients in the SHM marking group. There was no statistically significant difference in BCVA, UDVA, preexisting corneal astigmatism, or residual astigmatism between the groups before or after surgery ( P > 0.05). The mean toric IOL misalignment was lesser but without significance in the TRP marking group than in the SHM marking group after 3 postoperative months (2.66° ± 1.42° versus 3.29° ± 1.67°; P = 0.295). Conclusion . The TRP marking method using the iTrace aberrometer is simple and accurate for preoperative marking of toric IOLs. It can eliminate the potential systematic errors resulting from varying head positions during the preoperative keratometry measurement and from manual marking.

Purpose: The aim of the study was to investigate the signaling of growth hormone–releasing hormone receptor (GHRH-R) in the pathogenesis of pterygium and determine the apoptotic effect of GHRH-R antagonist on pterygium epithelial cells (PECs). Methods: Fourteen samples of primary pterygium of grade T3 with size of corneal invasion ≥ 4 mm were obtained for investigation by histology, immunofluorescence, electron microscopy, explant culture, and flow cytometry. Results: We found that PECs were localized in the basal layer of the epithelium in advancing regions of the head of pterygium. These cells harbored clusters of rough endoplasmic reticulum, ribosomes, and mitochondria, which were consistent with their aggressive proliferation. Immunofluorescence studies and Western blots showed that GHRH-R and the downstream growth hormone receptor (GH-R) were intensively expressed in PECs. Their respective ligands, GHRH and GH, were also elevated in the pterygium tissues as compared to conjunctival cells. Explanted PECs were strongly immunoreactive to GHRH-R and exhibited differentiation and proliferation that led to lump formation. Treatment with GHRH-R antagonist MIA-602 induced apoptosis of PECs in a dose-dependent manner, which was accompanied by a downregulation of ERK1 and upregulation of Caspase 3 expression. Conclusions: Our results revealed that GHRH-R signaling is involved in survival and proliferation of PECs and suggest a potential therapeutic approach for GHRH-R antagonist in the treatment of pterygium.

To report a case of femtosecond laser-assisted removal of an intracorneal chestnut. A chestnut was obliquely protruding to the stroma of cornea and it was localized at the paracentral region on the left eye of a 32-year-old man. The best-corrected visual acuity (BCVA, in decimal values) was 0.6 in the injured eye. The white ulcers with feathery edges or satellite infiltrates were not observed in the lesion, and the anterior chamber was deep and quiet. Anterior segment optical coherence tomography (AS-OCT) demonstrated that the original entry path of the foreign body had been sealed, spanning a thickness of approximate 152 μm. In view of location of the intraocular chestnut at the paracentral region, femtosecond laser was applied according to the procedures of IntraLase Enabled Keratoplasty (IEK) to create an anterior lamellar flap rapidly and precisely. The lamellar flap was easily separated with a flap lifter, and the chestnut was removed entirely using a pair of forceps. In 3 days after surgery, the patient complained of mild pain and blurred vision. These symptoms were relieved after treatment with the eyedrops. At three-month follow-up, the corneal wound was healed well, and the BCVA was greatly improved to 1.2 in the left eye. A dot-like haze was observed corresponding to the scar at the site of foreign body removal. No surgical induction of corneal astigmatism was found in the corneal topography. Without induction of a visually significant scar and corneal astigmatism, the IEK procedure of femtosecond laser is of particular interest as it provides a unique method for removal of intracorneal foreign bodies impinging on the visual axis.