Volume 61 · Issue 09 · 2025

This issue focuses on the research progress of glaucoma diagnosis and treatment. The responsible editorial committee responsible for the planning, composition and review of this issue is Professor Wang Tao.

The rise of minimally invasive glaucoma surgery (MIGS) has brought new options to glaucoma treatment. However, there are significant differences between MIGS and traditional trabeculectomy in terms of surgical philosophy, applicable populations, and long-term efficacy. As a classic procedure, trabeculectomy achieves a well-documented intraocular pressure (IOP)-lowering effect but is associated with a higher risk of complications. In contrast, MIGS features minimal invasiveness and rapid recovery, yet its IOP-lowering magnitude is limited, and its long-term efficacy remains a matter of debate. How to balance these two approaches, especially considering the varying availability of medical resources in China, represents a key challenge for Chinese clinicians. Drawing on the characteristics of Chinese glaucoma patients, the distribution of medical resources, and clinical practice experience, this paper explores in depth the indications, advantages, and limitations of MIGS and trabeculectomy, aiming to provide more targeted references for clinicians in China when selecting glaucoma surgical strategies.

As the world′s leading irreversible blinding eye disease, glaucoma is predominantly managed with pharmaceutical interventions in clinical practice. However, long-term use of traditional eye drops containing preservatives (e.g., benzalkonium chloride) may induce ocular surface toxicity, increase the incidence of dry eye, promote conjunctival fibrosis, and compromise the success rate of filtering surgery. In recent years, the field of ophthalmology has been actively advancing the research, development, and clinical application of preservative-free anti-glaucoma drugs. This article focuses on the research progress of preservative-free formulations in terms of innovative preparation technologies, characteristics of clinical benefits, and existing issues, while exploring their future development directions, aiming to provide references for clinical practice.

Primary angle-closure glaucoma (PACG) is a prevalent clinical condition. In 2019, the Glaucoma Group of Ophthalmology Branch of Chinese Medical Association released the consensus opinions on the diagnosis and treatment of PACG, providing crucial guidance for clinical practice. Since significant new research on PACG has emerged over the past five years, both the Glaucoma Group of Ophthalmology Branch of Chinese Medical Association and the Glaucoma Group of Chinese Ophthalmologist Association have collaborated to conduct extensive evidence-based discussions to attain an updated consensus on the classification, diagnostic approaches, and treatment principles for PACG in China, which may serve as a reference for clinical practitioners.

The prevalence of normal tension glaucoma (NTG) in China stands at 1%. The inappropriate demarcation of normal intraocular pressure values may lead to misdiagnosis. The Glaucoma Group of Ophthalmology Branch of Chinese Medical Association released the consensus on the diagnosis and treatment of NTG in 2019, which established important clinical guidelines for the NTG management. Since significant research advances have been made regarding NTG in recent years, the Glaucoma Group of Ophthalmology Branch of Chinese Medical Association, in collaboration with the Glaucoma group of Chinese Ophthalmologist Association, has developed updated evidence-based consensus recommendations through comprehensive expert discussions. This new consensus on the NTG diagnosis and treatment principles aims to serve as a practical reference for clinicians.

To investigate the treatment approaches for attacking eyes in patients with clinical acute primary angle-closure glaucoma (APACG) and their alignment with the recommendations in the Chinese Glaucoma Guidelines (2020).

A cross-sectional study was conducted, including medical records of consecutive inpatients diagnosed with APACG from 22 ophthalmic centers nationwide during three periods: September 7, 2020, to January 6, 2021; September 7, 2021, to January 6, 2022; and September 7, 2022, to January 6, 2023. For patients meeting the inclusion criteria in both eyes, the right eye was uniformly selected for analysis. Demographic characteristics, medical history, and ocular examination data were collected. Patients were categorized into medication group, laser treatment group, and surgical treatment group based on their final treatment after admission. The proportion of different treatment approaches and their consistency with the Chinese Glaucoma Guidelines (2020) were analyzed. Statistical analysis was performed using the chi-square test.

A total of 2 567 patients (2 567 eyes) with APACG were included, with a mean age of (66.7±9.3) years. Among them, 615 (24.0%) were male and 1 952 (76.0%) were female; 1 431 eyes (55.7%) were right eyes and 1 136 eyes (44.3%) were left eyes. There were 83 eyes (3.2%) in the medication group, 256 eyes (10.0%) in the laser treatment group, and 2 228 eyes (86.8%) in the surgical treatment group. In the surgical treatment group, 1 951 eyes (87.6%) underwent cataract extraction, and 1, 300 eyes (58.3%) received phacoemulsification combined with goniosynechialysis as the preferred surgical approach. The rate of complete consistency between the treatment regimens and the recommendations in the Chinese Glaucoma Guidelines (2020) was 52.4% (1 344/2 567), and the rate of partial consistency was 40.3% (1 035/2 567).

Phacoemulsification combined with goniosynechialysis has become the mainstream surgical approach for treating attacking eyes in APACG patients in China. Over 90% of APACG patients received treatment consistent with the Chinese Glaucoma Guidelines (2020).

To explore the effects of aging on the stiffness of human scleral fibroblast (HSF) and the remodeling of the extracellular matrix.

This experimental study was conducted from January 2022 to June 2024. HSFs were cultured, and after cell passage, β-galactosidase staining was conducted. The expression levels of aging markers P16 and P21 were detected through Western blotting. To establish a replicative aging model of HSF, cells were divided into two groups: the 4th generation cells as the young control group and the 16th generation cells as the aging experimental group. Atomic force microscopy was used to measure the stiffness of the cell bodies and the extracellular matrix produced by both groups, expressed as Young′s modulus, a measure of stiffness. The biological characteristics, including cell contractility, and the expression of extracellular matrix-related proteins in both groups were assessed through collagen gel contraction experiments and Western blotting. The expression levels of protein cross-linking indicators—lysyl oxidase (LOX), lysyl oxidase-like protein 1 (LOXL1), and transglutaminase (TGM2)—were measured at both mRNA and protein levels using quantitative real-time PCR and Western blotting. Statistical analysis was performed using independent samples t-test and Mann-Whitney U test.

HSF successfully established a replicative senescence model after passage, and when the cells were passed to the 16th generation, the positive rate of β-galactosidase staining significantly increased, the cell doubling time was prolonged, and the expression of p16 protein in the senescence experimental group (1.40±0.05) was higher than that in the young control group (0.87±0.11); the expression of p21 protein in the senescence experimental group (1.13±0.12) was higher than that in the young control group (0.79±0.04), with statistically significant differences (all P<0.05). The Young′s modulus of the cell bodies in the senescent group [2.259 (1.971, 2.745) kPa] was higher than that in the young control group [1.268 (1.068, 1.489) kPa]. Likewise, the Young′s modulus of the extracellular matrix in the senescent group [13.598 (9.073, 17.352) kPa] was higher than that in the young control group [10.050 (6.633, 14.999) kPa], with statistically significant differences (both P<0.001). The collagen gel contraction ability of the senescent group was lower than that of the young control group after 12, 24, 36, and 48 hours of culture, with values of 0.803±0.015, 0.773±0.021, 0.713±0.015, and 0.697±0.015 compared to 0.880±0.010, 0.833±0.015, 0.820±0.010, and 0.803±0.006, respectively. These differences were statistically significant (all P<0.05). After 48 hours of culture, the migration distance of cells in the senescence experimental group [(73.33±4.16) μm] was lower than that in the young control group [(187.33±3.06) μm], with a statistically significant difference (P<0.001). The expression levels of type Ⅰ collagen, anti-adhesion protein, and anti-fibronectin in the senescence experimental group were lower than those in the young control group [(0.153±0.009) vs. (0.250±0.012), (0.233±0.010) vs. (0.315±0.016)and (0.510±0.020) vs. (0.616±0.050)], with statistically significant differences (all P<0.05). The mRNA expression of LOX, LOXL1, and TGM2 in the senescence experimental group was higher than that in the young control group [(2.250±0.060) vs. (1.033±0.059), (2.565±0.153) vs. (1.002±0.019)and (2.985±0.138) vs.(1.023±0.050)], with statistically significant differences (all P<0.001). The protein expression of LOX, LOXL1, and TGM2 in the senescence experimental group was also higher than that in the young control group [(0.682±0.022) vs. (0.279±0.025), (0.602±0.012) vs. (0.230±0.027)and (0.723±0.010) vs. (0.331±0.036)], with statistically significant differences (all P<0.001).

In the HSF senescence model, the stiffness of senescent HSF and their associated extracellular matrix increased, while the expression levels of extracellular matrix component proteins decreased, but the expression levels of cross-linking proteins increased.

To explore the role and mechanism of the hypoxia-inducible factor-1 (HIF-1) pathway in rat retinal precursor R28 cell injury caused by the OPTN (E50K) mutation.

This experimental study was conducted from November 2023 to October 2024. The retinas of 18-month-old wild-type (WT) mice and normal tension glaucoma mice with the OPTN (E50K) mutation were extracted for proteomic analysis. In vitro models carrying the genes of green fluorescent protein (GFP), GFP-OPTN (WT) and GFP-OPTN (E50K) were constructed by transfecting R28 cells with adeno-associated viruses. Western blotting and PCR were used to detect the protein and mRNA expressions of apoptotic index B-lymphocytoma-2-associated X protein (BAX), HIF-1α, and energy metabolism enzymes including glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). R28 cells were treated with the HIF-1α inhibitor Lificiguat at concentrations of 0, 25, 50, 75 and 100 μmol/L for 12, 24 and 48 hours, respectively. According to the cell counting kit-8 detection results, 75 μmol/L Lificiguat was selected to treat the cells for 24 hours. The protein and mRNA expression changes of HIF-1α, GLUT1, LDHA and BAX were detected after the addition of Lificiguat. The statistical analysis was performed using the one-way analysis of variance and Tukey test.

There were 1 564 differentially expressed proteins in the retinas of mice in the experimental group compared with those in the control group, and these were significantly enriched in the HIF-1 signaling pathway. The protein expression levels of BAX, HIF-1α, GLUT1 and LDHA in OPTN (E50K) mutant R28 cells were 1.28±0.15, 1.54±0.21, 1.28±0.15 and 1.20±0.16, respectively. They were significantly increased compared with those in R28 cells transfected with the GFP-OPTN (WT) gene (0.96±0.04, 0.87±0.07, 0.90±0.10, 0.87±0.02; all P<0.05). The mRNA expression levels of BAX, HIF-1α, GLUT1 and LDHA in OPTN (E50K) mutant R28 cells were 1.20±0.06, 2.89±0.21, 2.37±0.22 and 1.27±0.22, respectively. They were also significantly increased compared with those in R28 cells transfected with the GFP-OPTN (WT) gene (0.87±0.14, 0.88±0.23, 1.24±0.18, 0.94±0.07; all P<0.05). The protein expression levels of HIF-1α, LDHA and BAX in OPTN (E50K) mutant R28 cells treated with Lificiguat were 0.62±0.11, 0.65±0.15 and 0.76±0.03, respectively. They were significantly decreased compared with those in OPTN (E50K) mutant R28 cells untreated with Lificiguat (0.88±0.04, 0.92±0.04, 1.08±0.07; all P<0.05). The mRNA expression levels of HIF-1α, LDHA and BAX in OPTN (E50K) mutant R28 cells treated with Lificiguat were 1.06±0.06, 1.11±0.14 and 1.01±0.01, respectively. They were also significantly decreased compared with those in OPTN (E50K) mutant R28 cells untreated with Lificiguat (1.34±0.09, 1.45±0.14, 1.12±0.00; all P<0.05). The protein expression levels of GLUT1 in OPTN (E50K) mutant R28 cells without and with Lificiguat were 0.99±0.10 and 1.09±0.01, while the mRNA expression levels were 1.23±0.06 and 1.31±0.13, respectively. The expression of the GLUT1 protein and mRNA in OPTN (E50K) mutant R28 cells slightly increased after treatment with Lificiguat, and there was no statistically significant difference (all P>0.05).

The OPTN (E50K) mutation affects the expression of energy metabolism enzymes GLUT1 and LDHA in R28 cells by regulating the HIF-1 pathway, inducing apoptosis of R28 cells. Lificiguat can effectively inhibit the overexpression of HIF-1α caused by the OPTN (E50K) mutation and protect R28 cells.

To explore optimized protocols for paraffin section preparation of the eyeball to enhance the histological visualization of key ocular structures.

It was an experimental research, conducted from September 2022 to September 2024. The first experiment involved 18 porcine eyeballs, which were divided into five groups (six subgroups) by the random number table method. Three fixatives were tested: Davidson′s solution (Davidson group), a mixture of 1% paraformaldehyde and 1.25% glutaraldehyde (mixed solution group), and 4% paraformaldehyde (formaldehyde group). Each fixative was applied at room temperature and 4 ℃, respectively. Hematoxylin and eosin-stained paraffin sections were prepared and evaluated for basic quality and morphological conditions of the cornea, lens, anterior chamber angle, ciliary body, Zinn′s zonule, sclera, and retina. In the second experiment, 33 porcine eyeballs were divided into 4 groups (11 subgroups) by the random number table method to assess the effects of different pre-fixation treatments. The section quality was scored and compared among the groups of commonly used clinical dissection methods, standard anatomical procedures, hemisected eyeballs, and untreated controls. The optimal pre-treatment and fixation conditions were then validated using six human eyeballs (three from elderly males and three from male adolescents). Statistical analyses were performed using the Kruskal-Wallis H test, Dunn test, Bonferroni correction, paired-sample t-test, and Mann-Whitney U test.

The Davidson group exhibited a rough globe surface, opacified lens, and blackened sclera. In contrast, the mixed solution group maintained a smooth surface, yellowing of the cornea and sclera, and lens transparency. The formaldehyde group also had a smooth surface, but the lenses appeared slightly opaque. The mixed solution group showed significantly higher scores for lens morphology (8.00±1.95) and Zinn′s zonule (3.17±1.27) than the Davidson group (6.17±1.03 and 1.83±0.94, both P<0.05), and for Zinn′s zonule and retinal morphology (5.58±1.83) compared to the formaldehyde group (1.50±0.67 and 2.92±0.79, both P<0.05). The anterior segment total score (27.67±4.74) was significantly higher in the mixed solution group than the Davidson group (22.83±2.98, P<0.05). The anterior segment total score and overall section quality score (40.58±7.53) were significantly higher in the mixed solution group than the formaldehyde group (23.17±3.04 and 32.42±4.01, both P<0.05). The 4 ℃ fixation condition yielded better preservation of Zinn′s zonule (2.50±1.04) compared to room temperature fixation (1.83±1.29, P<0.05). Among the pre-treatment methods, the clinical approach group achieved higher scores in ciliary body (7.04±1.30), Zinn′s zonule (2.96±0.95), sclera (6.63±1.38), retina (5.17±1.58), and total section quality (36.75±4.63), compared to hemisected specimens (all P<0.05). Application of the optimal pre-treatment method (0.5-cm corneal limbal incision) and fixation condition (mixed solution at 4 ℃) to human eyeballs successfully preserved and ensured clear visualization of the key structures, including the ciliary body, lens, Zinn′s zonule, and ocular wall.

The pre-treatment using a clinical method (e.g., corneal limbal incision), combined with 4 ℃ fixation in a paraformaldehyde-glutaraldehyde mixture, significantly enhances the preservation and visualization of essential ocular structures in paraffin sections. This method shows promise for improving the histopathological evaluation of the human eyeball.

To assess the current research status of retinal vein occlusion (RVO) and to explore its research trends and hotspots based on bibliometrics.

A bibliometric study was conducted on April 25, 2024, retrieving articles from China National Knowledge Infrastructure (CNKI), Wanfang, and Web of Science Core Collection covering 2014 to 2023. CiteSpace, VOSviewer, and Microsoft Excel were used for visualization and analysis of annual publications, country distribution, author productivity, journals, cited references, and keywords.

A total of 1 929 articles in Chinese and 2 764 international publications were identified. The ophthalmology journals dominated the publication venues. Retina-The Journal of Retinal and Vitreous Diseases published the highest number of foreign-language articles (n=178), accounting for 6.44% of the international literature analyzed. International Eye Science published the highest number of Chinese-language articles (n=140), accounting for 7.26% of the Chinese literature analyzed. Research on RVO followed an interdisciplinary development pattern, with research hotspots primarily focused on ophthalmology, molecular biology, and immunology. The U.S. produced the largest volume of papers (659), followed by China (481), while France achieved the highest citation impact (average 28.19 citations per article). Akitaka Tsujikawa was the most prolific foreign author (41 papers, 479 citations, average 10.89 citations per paper). The keyword analysis extracted 373 and 823 keywords from the Chinese and foreign literature, respectively, with major bursts in 2015 and 2020. The early studies focused on clinical and pathological features; recent research emphasized molecular mechanisms, novel drugs, and therapies. The keyword clustering identified 17 and 6 significant clusters in the Chinese and foreign literature, respectively. The topics such as macular edema, ranibizumab, vascular endothelial growth factor, and quality of life emerged in 2015 and remained as central priorities.

RVO and macular edema are primary research foci both domestically and internationally. Macular edema, ranibizumab, vascular endothelial growth factor, and quality of life have become enduring hotspots within the field of RVO research over the past decade.

Two patients (a 7-year-old female and a 61-year-old male) had poor intraocular pressure control after XEN gel stent implantation. During the process of filtering bleb repair, the XEN gel implant retreated into the anterior chamber, and the limbal and corneal incisions were made. After the implant in the anterior chamber was taken out, it was implanted into the anterior chamber again from the original scleral tunnel for the female patient, while it was re-punctured into the anterior chamber with a 1-ml syringe needle at another site for the male patient. The follow-up examinations at 3 weeks and 6 months after surgery showed good results.

A 65-year-old male patient presented with "blurred vision in the right eye for 1 week". At the first visit, the best corrected visual acuity (BCVA) of both eyes was 0.8, no obvious abnormalities were observed in fundus examination, and optical coherence tomography (OCT) revealed the loss of outer retinal layers adjacent to the macula in the right eye. Ten days after the initial visit, the visual acuity of both eyes declined. OCT showed loss of outer retinal layers in both eyes except for the macular area, accompanied by short-term visual acuity decrease and binocular visual field defects. Electroretinography (ERG) demonstrated decreased amplitudes of a-waves and b-waves in both eyes under light and dark adaptation. Combined with imaging findings of lung squamous cell carcinoma and positive anti-recoverin antibody, the clinical diagnosis was lung squamous cell carcinoma-associated retinopathy.

The patient was a 25-year-old male. He went to the Department of Ophthalmology of Qingdao Municipal Hospital due to redness and pain in his right eye with visual acuity decrease for 1 week. Has a history of ankylosing spondylitis and has suffered from iritis. The specific condition is unknown. Eye examination: the naked eye visual acuity of the right eye was 0.5 and the corrected visual acuity was 0.6; The naked visual acuity of the left eye was 0.6 and the corrected visual acuity was 1.0; IOP was 43 mmHg (1 mmHg =0.133 kPa) in the right eye and 18 mmHg in the left eye; The conjunctiva of the right eye is mixed and congested (+ +), the cornea is transparent, the anterior chamber is shallow, the peripheral anterior chamber nearly disappears, the aqueous humor cells (+ + +), the aqueous humor flashes (+ +), the iris is obviously swollen, the pupil is round, about 2 mm in diameter, the posterior adhesion of the pupil margin, the lens is slightly opaque, and the iris pigment is visible on the surface; Fundus blurred. No obvious abnormalities were observed in the anterior segment of the left eye. Anterior segment coherence light tomography examination: the anterior chamber of the right eye is shallow, with scattered punctate weak echoes, the iris bulges arcuately toward the anterior chamber, showing hump-like changes, the root of the iris is in contact with the corneal endothelium, the angle of the chamber is closed, and the iris of the pupil margin is in contact with the anterior capsule of the lens (A in Quintessential Picture 1); No obvious abnormalities were observed in the left eye. Clinical ophthalmological diagnosis: Acute iridocyclitis of right eye; Secondary glaucoma of the right eye. Laser peripheral iridectomy of the right eye was performed with yttrium aluminum garnet. The intraocular pressure in the right eye decreased to 18 mmHg after operation; Mixed conjunctiva congestion (+ + +) in the right eye, local roughness of corneal epithelium, deepening of anterior chamber, visible tissue fragments and pigment particles, flat iris, elliptical laser hole in the peripheral iris at 2: 00, a small amount of bleeding below, and thin exudative membrane in the pupil area. Anterior segment coherence optical tomography examination: the depth of the anterior chamber of the right eye is moderate, with a large number of dense punctate weak echoes, flat iris, penetrating laser hole at 2: 00, open chamber angle, and membranous moderately strong echoes in the pupil area (B in Quintessential Picture 1).

Pathological myopia is one of the primary causes of irreversible visual loss in the population. Myopic maculopathy represents a key feature of pathological myopia, among which macular atrophy is the main contributor to severe visual impairment. The specific mechanism underlying the development of macular atrophy remains unclear. Studies have demonstrated that the formation and progression of choroidal neovascularization are closely linked to the onset of macular atrophy. To date, no effective therapeutic interventions have been identified to delay or reverse the progression of macular atrophy.

Angle closure glaucoma is one of the important types of glaucoma in China, and a considerable number of patients with secondary glaucoma and complex refractory glaucoma have extensive angle closure. The feasibility and effectiveness of modern minimally invasive glaucoma surgery in these angle-closure glaucomas still lacks clinical experience and high-level evidence-based evidence. This article summarizes the application of all kinds of minimally invasive glaucoma surgery in angle-closure glaucoma at present, and puts forward views and thinking combined with clinical practice, in order to provide ideas and support for clinical diagnosis and treatment.

Uveitis is a common and important extra-articular manifestation of juvenile idiopathic arthritis (JIA), primarily characterized by chronic anterior uveitis. It has an insidious clinical onset, and if not timely diagnosed and treated, it can lead to severe and irreversible visual impairment. This article reviews and summarizes the treatment strategies for JIA-associated uveitis, including local treatments (corticosteroid eye drops, local injection therapy), systemic treatments (corticosteroids, conventional immunosuppressive agents, biologics, and small molecule targeted drugs), and research progress in surgical treatment. It aims to provide a reference for clinical practice and thereby improve patient prognosis by optimizing treatment plans.