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Gene Feb 2024Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle... (Review)
Review
Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle glaucoma with subtypes like POAG, ACG, XFG, PCG, PDG, and developmental glaucoma. The pathophysiological and genetic factors behind glaucoma remain partially understood, with past studies linking intraocular pressure (IOP) levels to retinal ganglion cell death. Open-angle glaucoma involves elevated resistance to aqueous outflow via the trabecular meshwork, while angle-closure glaucoma typically sees drainage pathways obstructed by the iris. Genes have been identified for POAG, ACG, XFG, PCG, PDG, and developmental glaucoma, allowing for early-onset detection and the emergence of gene therapy as an effective treatment. Nevertheless, diagnostic and treatment options have their constraints, necessitating large-scale, well-designed studies to deepen our grasp of genetics' role in glaucoma's pathogenesis. This review delves into glaucoma's risk factors, pathophysiology, genetics, diagnosis, and available treatment options, including gene therapy. Additionally, it suggests alternative therapies like yoga and meditation as adjunct treatments for glaucoma prevention. Overall, this review advances our comprehension of the pathophysiology and genetic associations of glaucoma while highlighting the potential of gene therapy as a treatment avenue. Further research is imperative to fully elucidate the genetic mechanisms underpinning glaucoma and to devise effective treatments.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma; Trabecular Meshwork; Optic Nerve; Intraocular Pressure
PubMed: 37952746
DOI: 10.1016/j.gene.2023.147983 -
Clinical Ophthalmology (Auckland, N.Z.) 2023To report the prevalence, clinical characteristics and risk factors for paracentral acute middle maculopathy (PAMM) following acute primary angle closure (APAC) and...
PURPOSE
To report the prevalence, clinical characteristics and risk factors for paracentral acute middle maculopathy (PAMM) following acute primary angle closure (APAC) and acute primary angle closure glaucoma (APACG).
METHODS
This retrospective study consecutively recruited patients diagnosed with APAC or APACG. Based on the spectral domain optical coherence tomography characteristics, PAMM eyes were divided into three stages. Characteristics of different stages such as the time from symptoms to treatment (TST), retinal thickness and BCVA improvement were analyzed. The risk factors of PAMM were evaluated by binary logistic regression models.
RESULTS
A total of 781 eyes of 781 APAC or APACG patients were included, and PAMM was found in 22 (2.9%) of them. Stage III eyes had a significantly longer TST than stage I eyes ( = 0.008) while exhibiting significantly thinner retinal thicknesses ( < 0.0001). The BCVA improvement was significantly worse in the eyes treated in stage III than in those treated in stage I ( = 0.008). Older age, longer axial length and without type 2 diabetes were associated with a lower risk of incident PAMM (OR = 0.95, = 0.028; OR = 0.52, = 0.019; OR = 3.92, = 0.022).
CONCLUSION
PAMM can be secondary to APAC or APACG at a rate of 2.9%. Different visual outcomes were observed in patients who received the intervention at different stages of PAMM. Younger patients with a shorter axial length and type 2 diabetes were found to be more susceptible to PAMM.
PubMed: 38026591
DOI: 10.2147/OPTH.S437075 -
Journal of Clinical Medicine Aug 2023We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).
BACKGROUND
We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).
METHODS
A retrospective analysis was performed on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM).
RESULTS
No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance, longer whole eye movement, and longer whole eye movement time than patients with POAG. The highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL.
CONCLUSIONS
The biomechanical properties of the cornea differed between POAG and PACG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.
PubMed: 37568510
DOI: 10.3390/jcm12155108 -
Die Ophthalmologie May 2024
PubMed: 38713218
DOI: 10.1007/s00347-024-02045-1 -
The Application of Clinical Genetics 2023Bilateral secondary angle closure glaucoma is a presenting symptom of microspherophakia and ectopia lentis. Characterizing the associated syndrome and confirmation by...
BACKGROUND
Bilateral secondary angle closure glaucoma is a presenting symptom of microspherophakia and ectopia lentis. Characterizing the associated syndrome and confirmation by genetic testing can identify associated systemic abnormalities and provide appropriate genetic counseling.
CASE PRESENTATION
A 42-year-old woman with severe intellectual disability presented with light perception visual acuity and glaucoma, with intraocular pressure (IOP) in her right and left eyes of 69 and 70 mmHg, respectively. She underwent two sessions of 270-degree laser diode transscleral cytophotocoagulation treatment at a 6-month interval and was prescribed topical anti-glaucoma medication. Her family noticed a progressive decrease in her vision while on treatment for 2 years. She was diagnosed with apparent Weill-Marchesani syndrome, accompanied by angle closure glaucoma and microspherophakia. Cataract surgery and intraocular lens implantation were successful in both eyes and post-operative IOP was controlled with anti-glaucoma medication but her vision did not improve from severe glaucomatous optic neuropathy. Her underlying syndrome was investigated genetically by whole exome sequencing.
RESULTS
Sequencing showed a pathogenic variant in , c.3955dupC (p.Gln1319Profs*14), diagnostic of Coffin-Siris syndrome. This is the first report of Coffin-Siris syndrome associated with microspherophakia and angle closure glaucoma.
CONCLUSION
Bilateral angle closure glaucoma from ectopia lentis in patients with genetic syndromes could be an indicator of microspherophakia in adulthood. Ophthalmological surveillance is important in patients with Coffin-Siris syndrome.
PubMed: 37663124
DOI: 10.2147/TACG.S422312 -
ELife Feb 2024Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used...
BACKGROUND
Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.
METHODS
Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.
RESULTS
Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression.
CONCLUSIONS
Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.
FUNDING
This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).
Topics: Humans; Androstenedione; Bayes Theorem; Biomarkers; China; Cross-Sectional Studies; Glaucoma, Angle-Closure; Prospective Studies; Visual Fields
PubMed: 38358793
DOI: 10.7554/eLife.91407 -
Journal of Clinical Medicine Feb 2024To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). : A systematic literature search following PRISMA guidelines was conducted... (Review)
Review
To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). : A systematic literature search following PRISMA guidelines was conducted using the PubMed, Embase, Scopus and Cochrane databases from 1995 up to 28 August 2023. : Thirty studies out of the 520 records screened met the inclusion criteria and were included. Most articles (n = 20) analysed the association between pseudoexfoliation syndrome (XFS) and HL, showing XFS patients to have higher prevalence of sensorineural hearing loss (SNHL) at both speech frequencies (0.25, 0.5, 1 and 2 kHz), and higher frequencies (4 and 8 kHz) compared to controls in most cases. No significant differences in prevalence or level of HL between XFS and pseudoexfoliative glaucoma (XFG) were detected in most studies. Eight articles analysed the relationship between primary open-angle glaucoma (POAG) and HL. Overall, a positive association between the two conditions was highlighted across all studies except for two cases. Similarly, articles focusing on NTG and HL (n = 4) showed a positive association in most cases. The role of autoimmunity and, in particular, the presence of antiphosphatidylserine antibodies (APSA) in patients with NTG and HL suggested an underlying autoimmune or vascular mechanism contributing to their pathogenesis. Only one study analysed the relationship between angle-closure glaucoma (ACG) and HL, showing higher incidence of ACG in patients with SNHL compared to normal hearing controls. : Most studies detected an association between XFS and HL as well as POAG/NTG/ACG and HL, suggesting the presence of a similar pathophysiology of neurodegeneration. However, given the strength of the association of XFS with HL, it remains unclear whether the presence of XFG is further associated with SNHL. Further research specifically targeted to assess the correlation between glaucoma, XFS and HL is warranted to provide a more comprehensive understanding of this association.
PubMed: 38592217
DOI: 10.3390/jcm13051379 -
BMC Ophthalmology Nov 2023To report the ocular characteristics and management of three cases of retinitis pigmentosa (RP) concurrent primary angle closure glaucoma (PACG).
BACKGROUND
To report the ocular characteristics and management of three cases of retinitis pigmentosa (RP) concurrent primary angle closure glaucoma (PACG).
CASE PRESENTATION
Three middle-aged patients presenting with diminished vision, high intraocular pressure (IOP), and typical fundus manifestations of RP were clinically evaluated. The individualized treatment was based on the ocular conditions of each case. A novel genetic alteration in ZNF408 was identified in one patient. Two patients with short-axial eyes received unilateral combined trabeculectomy, cataract surgery, and Irido-zonulo-hyaloid-vitrectomy. One of them had a subluxated lens, managed with a capsular tension ring implantation. Their contralateral eyes, respectively, underwent laser peripheral iridotomy (LPI) and transscleral cyclophotocoagulation. The third patient underwent bilaterally combined laser peripheral iridoplasty, LPI, and medication. Ultimately, all patients achieved the target IOP during a two-year follow-up.
CONCLUSION
Young patients with RP may have a risk of developing angle closure glaucoma, and conversely, patients with angle closure glaucoma at younger age should be aware of the presence of RP. Therefore, routine gonioscopy and IOP monitoring are required for RP patients, and detailed fundus examinations are warranted for young PACG patients.
Topics: Middle Aged; Humans; Glaucoma, Angle-Closure; Iridectomy; Iris; Treatment Outcome; Laser Therapy; Retinitis Pigmentosa; Intraocular Pressure; DNA-Binding Proteins; Transcription Factors
PubMed: 37968604
DOI: 10.1186/s12886-023-03190-y -
American Journal of Ophthalmology Feb 2024To compare the effect of filtering surgery versus clear lens extraction in young patients with medically uncontrolled angle-closure glaucoma (ACG). (Comparative Study)
Comparative Study
PURPOSE
To compare the effect of filtering surgery versus clear lens extraction in young patients with medically uncontrolled angle-closure glaucoma (ACG).
DESIGN
Retrospective, nonrandomized, comparative, interventional study.
METHODS
We reviewed the medical charts of patients with the following scenarios: (1) age ≤40 years; (2) diagnosis of ACG without cataract, including primary angle-closure glaucoma (PACG), nanophthalmic ACG, and ACG combined with retinal dystrophies; and (3) ACG undergoing filtering surgery or clear lens extraction. The main outcomes including intraocular pressure (IOP), number of medications, best-corrected visual acuity, and severe complications were extracted at the postoperative early (within 1 week) and late stage (>3 months) follow-up.
RESULTS
Data from 160 eyes of 130 young patients with ACG were available. Eyes with 76 PACG, 12 nanophthalmic ACG, and 26 ACG with retinal diseases underwent filtering surgery, whereas eyes with 22 PACG, 12 nanophthalmic ACG, and 12 ACG with retinal diseases received clear lens extraction. Overall, filtering surgery and clear lens extraction resulted in significant but comparable IOP and drug reductions at the postoperative late stage in each ACG subgroup, with similar complete success rates between 2 treatments (all P > .05). Regarding the safety, filtering surgery and patients with retinal diseases were independent factors associated with postoperative malignant glaucoma (P < .05 in both multivariable logistic regression models).
CONCLUSIONS
This study highlights that the efficacy of clear lens extraction is comparable to that of filtering surgery in medically uncontrolled ACG in young patients, but clear lens extraction is safer, especially for young patients with ACG comorbid with retinal diseases.
Topics: Adult; Humans; Filtering Surgery; Glaucoma, Angle-Closure; Intraocular Pressure; Retinal Diseases; Retrospective Studies
PubMed: 37543298
DOI: 10.1016/j.ajo.2023.07.025 -
Translational Vision Science &... Sep 2023The purpose of this study was to investigate the classification of angle closure eyes based on hierarchical cluster analysis of ocular biometrics measured in the dark...
PURPOSE
The purpose of this study was to investigate the classification of angle closure eyes based on hierarchical cluster analysis of ocular biometrics measured in the dark and light using anterior segment optical coherence tomography (AS-OCT).
METHODS
Participants of the Chinese American Eye Study received complete eye examinations to identify primary angle closure suspects (PACS) and primary angle closure without/with glaucoma (PAC/G). AS-OCT was performed in the dark and light. Biometric parameters describing the angle, iris, lens, and anterior chamber were analyzed. Hierarchical clustering was performed using Ward's method. Post hoc logistic regression models were developed to identify biometric predictors of angle closure staging.
RESULTS
Analysis of 159 eyes with PACS (N = 120) or PAC/G (N = 39) produced 2 clusters in the dark and light. In both analyses, cluster 1 (N = 132 in the dark and N = 126 in the light) was characterized by smaller angle opening distance (AOD)750 and trabecular iris space area (TISA)750, greater iris curvature (IC), and greater lens vault (LV; P < 0.001) than cluster 2. The proportion of PAC/PACG to PACS eyes was significantly higher in cluster 1 than 2 in the light (36:90 and 3:30, respectively; P = 0.02), but not the dark (36:96 and 3:24, respectively; P = 0.08). On multivariable regression analyses, smaller TISA750 (odds ratio [OR] = 0.84 per 0.01 mm2) and AOD750 (OR = 0.93 per 0.01 mm) in the light and smaller TISA750 (OR = 0.86 per 0.01 mm2) in the dark conferred higher risk of PAC/G (P ≤ 0.02).
CONCLUSIONS
Unsupervised cluster analysis of ocular biometrics can classify angle closure eyes by severity. Static biometrics measured in the light and dark are both predictive of PAC/G.
TRANSLATIONAL RELEVANCE
Clustering of biometrics measured in the light could provide an alternative source of information to risk-stratify angle closure eyes for more severe disease.
Topics: Humans; Anterior Chamber; Glaucoma; Tomography, Optical Coherence; Biometry; Cluster Analysis
PubMed: 37672252
DOI: 10.1167/tvst.12.9.4