Background and Objectives: Several studies suggest the complex relationship between Endothelin-1 (ET-1) levels with various types of glaucoma. This systematic review and meta-analysis explore ET-1 levels in plasma and aqueous humor among different types of glaucoma. Materials and Methods: A literature search (PubMed, ScienceDirect, Cochrane Library) was made up to April 2024 (PROSPERO: CRD42023430471). The results were synthesized according to PRISMA Guidelines. Results were presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 2597 subjects (1513 patients with glaucoma vs. 1084 healthy controls) from 23 studies were included in a meta-analysis. Notably, patients with glaucoma reported significantly higher plasma levels of ET-1 compared to controls (SMD: 1.21, 95% CI: 0.59-1.82, p < 0.001). Particularly, plasma ET-1 levels were higher in primary open-angle glaucoma (POAG) (SMD: 0.87, 95% CI: 0.09-1.65, p < 0.05), normal-tension glaucoma (SMD: 0.86, 95% CI: 0.27-1.46, p = 0.05), and angle-closure glaucoma patients (SMD: 1.03, 95% CI: 0.43-1.63, p < 0.001) compared to healthy controls. Moreover, ET-1 aqueous humor levels were significantly higher in patients with glaucoma compared to controls (SMD: 1.60, 95% CI: 1.04-2.15, p < 0.001). In particular, aqueous humor levels were higher in POAG patients (SMD: 2.03 95% CI: 1.00-3.14, p < 0.001), and pseudoexfoliative glaucoma patients (SMD: 2.03, 95% CI: 1.00-3.07, p < 0.001) compared to controls. Conclusions: This meta-analysis indicates that elevated levels of ET-1 plasma and aqueous humor are significantly associated with different types of glaucoma. The pathogenesis of ET-1-related mechanisms may vary across different glaucoma types, indicating that possible therapeutic approaches targeting ET-1 pathways should be tailored to each specific glaucoma type.

This article aims to provide a comprehensive review of the biochemical changes observed in the anterior chamber of the eye in diabetic patients. The increased levels of inflammatory markers, alterations in antioxidant defense mechanisms, and elevated levels of advanced glycation end products (AGEs) in the aqueous humor (AH) are explored. Additionally, the impact of these biochemical changes on diabetic retinopathy progression, increased intraocular pressure, and cataract formation is discussed. Furthermore, the diagnostic and therapeutic implications of these findings are presented. This study explores potential biomarkers for detecting diabetic eye disease at an early stage and monitoring its progression. An investigation of the targeting of inflammatory and angiogenic pathways as a potential treatment approach and the role of antioxidant agents in managing these biochemical changes is performed.

OBJECTIVE: To report a challenging Descemet Membrane Endothelial Keratoplasty (DMEK) case, complicated by intraoperative aqueous misdirection and spontaneous anterior chamber fibrin reaction.
METHODS: A 70-year-old female affected by corneal edema due to Fuchs endothelial dystrophy underwent a triple procedure (cataract extraction - IOL implantation - DMEK surgery) in her left eye. This report illustrates the management of the intraoperative complications of aqueous misdirection syndrome and anterior chamber fibrin reaction.
RESULTS: Despite the optimal management of the posterior pressure and the thorough removal of the fibrinous reaction during the case, the DMEK graft was not completely unfolded and centred at the end of the surgical procedure. Nonetheless, the patient showed good long-term anatomical and functional recovery: at the last follow-up (2 years after surgery), central corneal thickness was 526 µm with a best corrected visual acuity of 20/25 and an endothelial cell density of 1112 cell/mm2.
CONCLUSIONS: Early recognition and prompt management of intraoperative aqueous misdirection syndrome and anterior chamber fibrin reaction during DMEK surgery is essential to ensure good functional and anatomical outcomes.

OBJECTIVE: Myopia is one of the most common forms of refractive error. Most myopia manifests itself as a relative growth of the eye axis, resulting in a state in which light is projected in front of the retina after being refracted by the refractive system of the eyeball. So far, the specific pathogenesis of myopia is still not well explained, through the results of animal experiments, researchers have proposed various possible scenarios, but all these are based on animal models, and there may still be a certain gap with the mechanism of true myopia in humans. The most readily available in clinical work is aqueous humor obtained during cataract surgery, for which we reviewed these studies of aqueous humor samples from myopic patients.
METHODS: A systematic literature search was done on PubMed using key words including \"myopia,\" \"aqueous humor,\" and \"protein.\"
RESULTS: The results of existing aqueous humor studies have shown that the difference in substances in the aqueous humor of myopia is related to the degradation of the scleral matrix, chronic inflammation of the eye, pro-fibrosis, blood vessel production, and inhibition. There may be more than one reason associated with myopia progression.
CONCLUSIONS: The specific mechanism of myopia has not been fully elucidated. Therefore, the means of preventing and treating myopia should focus on inhibiting the degradation of the scleral matrix, promoting the proliferation of scleral collagen fibers, and alleviating chronic inflammation of the eyes. Further research into myopic aqueous humor may provide us with new insights.

BACKGROUND: Generally, there is no lipoprotein in aqueous humor, and chyle usually exists transiently in the body. Therefore, persistent chylous aqueous humor is rare.
METHODS: We report a case of a 39-year-old man with persistent milky white appearance over the right eye.
METHODS: The patient had a history of poorly controlled diabetes for the past 2 years and central retinal vein occlusion of the same eye for the past 2 weeks. The patient\'s right eye had a uniform milky appearance in the anterior chamber, transparent cornea, and no keratic precipitate in the posterior cornea. Color Doppler ultrasound of the affected eye showed no obvious inflammation in the vitreous cavity. Laboratory tests revealed severe chylemia. The patient was finally diagnosed as chylous aqueous humor.
RESULTS: After conventional hypolipidemia and hypoglycemia treatment and locally glucocorticoid treatment. The milky white changes in the anterior chamber improved considerably and finally disappeared.
CONCLUSIONS: Although the impact of hyperlipidemia on the cardiovascular system and digestive system is well known, its impact on the eyes is often overlooked. We report a rare case of unilateral chylous aqueous humor caused by hyperlipidemia. Through the analysis of this special case, we recommend that ophthalmologists should pay attention to the impact of blood lipid change on eyes.

OBJECTIVE: This scoping review summarizes the applications of artificial intelligence (AI) and bioinformatics methodologies in analysis of ocular biofluid markers. The secondary objective was to explore supervised and unsupervised AI techniques and their predictive accuracies. We also evaluate the integration of bioinformatics with AI tools.
METHODS: This scoping review was conducted across five electronic databases including EMBASE, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception to July 14, 2021. Studies pertaining to biofluid marker analysis using AI or bioinformatics were included.
RESULTS: A total of 10,262 articles were retrieved from all databases and 177 studies met the inclusion criteria. The most commonly studied ocular diseases were diabetic eye diseases, with 50 papers (28%), while glaucoma was explored in 25 studies (14%), age-related macular degeneration in 20 (11%), dry eye disease in 10 (6%), and uveitis in 9 (5%). Supervised learning was used in 91 papers (51%), unsupervised AI in 83 (46%), and bioinformatics in 85 (48%). Ninety-eight papers (55%) used more than one class of AI (e.g. > 1 of supervised, unsupervised, bioinformatics, or statistical techniques), while 79 (45%) used only one. Supervised learning techniques were often used to predict disease status or prognosis, and demonstrated strong accuracy. Unsupervised AI algorithms were used to bolster the accuracy of other algorithms, identify molecularly distinct subgroups, or cluster cases into distinct subgroups that are useful for prediction of the disease course. Finally, bioinformatic tools were used to translate complex biomarker profiles or findings into interpretable data.
CONCLUSIONS: AI analysis of biofluid markers displayed diagnostic accuracy, provided insight into mechanisms of molecular etiologies, and had the ability to provide individualized targeted therapeutic treatment for patients. Given the progression of AI towards use in both research and the clinic, ophthalmologists should be broadly aware of the commonly used algorithms and their applications. Future research may be aimed at validating algorithms and integrating them in clinical practice.

OBJECTIVE: To compare the VEGF levels in the aqueous humor of patients with Primary Open Angle Glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically significant correlations.
METHODS: We searched PubMed, from inception to December 31, 2021. Key search terms included VEGF and Glaucoma. All relevant studies that evaluated the VEGF levels in patients with POAG and in the control group were included in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Data were extracted independently by 2 authors. Heterogeneity was statistically quantified by Q, H, and I2 statistics, and a meta-analysis was performed using the random-effects model.
RESULTS: Seven cross-sectional studies were included in the meta-analysis. 144 eyes were enrolled in the POAG group and 162 eyes in the control group. The random effect model showed no statistically significant difference between the two groups (SMD =0.284, 95% CI = -0.173 to 0.741; P = 0.223), but we noticed a trend towards elevated VEGF levels in the aqueous humor of POAG patients. Significant heterogeneity was detected (I2 = 74.1%, P = 0.001).
CONCLUSIONS: This systematic review and meta-analysis indicates a trend towards elevated VEGF-A levels in the aqueous humor of patients with POAG and suggests a potential neuroprotective role of VEGF in patients with POAG. Future studies are required to evaluate the exact role of VEGF in POAG.

Recently, the quest for novel glaucoma surgical techniques and devices has been underway. Trabeculectomy remains the gold standard, but it requires the implantation of glaucoma drainage devices and frequent follow-ups, and it also carries a high risk of serious complications. The need for less invasive and safer procedures has led to the development of minimally invasive glaucoma surgery (MIGS), particularly for patients with mild-to-moderate disease. Among them, minimally invasive bleb surgery seems to be effective in classical glaucoma surgery, while maintaining MIGS benefits. The relatively new PreserFlo® MicroShunt (Santen, Osaka, Japan) is registered in Europe. It was released in 2019 for the treatment of patients with early-to-advanced open-angle glaucoma, where intraocular pressure (IOP) remains uncontrolled while on maximum tolerated medication and/or where glaucoma progression warrants surgery. This review focuses on the place of the PreserFlo MicroShunt, characterized by ab externo implantation, among MIGS procedures, discussing its advantages and disadvantages. The mechanisms of action, technical aspects, efficacy, and safety issues are summarized. The surgical technique, its efficacy, and safety profile are described, and directions for future studies are indicated. The PreserFlo MicroShunt ensures a high safety profile, minimal anatomical disruption, meaningful IOP-lowering effect, and ease of use for patients and physicians.

Cataracts are one of the most common causes of effective vision loss. Although most cases of cataracts are related to the ageing process, identifying modifiable risk factors can prevent their onset or progression. Many studies have suggested that micro and macroelement levels, not only in blood serum but also in the lens and aqueous humour, may affect the risk of the occurrence and severity of cataracts. This systematic review aims to summarise existing scientific reports concerning the importance of trace elements in cataractogenesis. Many authors have pointed out elevated or decreased levels of particular elements in distinct ocular compartments. However, it is not known if these alterations directly affect the increased risk of cataract occurrence. Further studies are needed to show whether changes in the levels of these elements are correlated with cataract severity and type. Such information would be useful for determining specific recommendations for micronutrient supplementation in preventing cataractogenesis.

UNASSIGNED: Retinoblastoma (RB) is the most common intraocular malignancy in children. The diagnosis of RB is mainly based on clinical features and imaging characteristics. Prognosis is based on stage of disease and response to treatment. In salvaged globes, direct tumor biopsy for genetic analysis and prognostication is an absolute contraindication at this point of time for the fear of extraocular tumor spread. Currently, there is a search for surrogate markers to allow accurate diagnosis and for prognostication, to predict the chances of globe salvage in RB. Therefore, biofluids such as plasma or aqueous humor have been studied to detect circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA), respectively, to allow for treatment decision making, monitoring treatment response, and prognostic counselling.
UNASSIGNED: A search of electronic databases (PubMed, Google Scholar and MEDLINE) of all articles on liquid biopsy in retinoblastoma published in English was performed. The keywords used for the search included \"retinoblastoma\", \"liquid biopsy\", \"aqueous humor\" \"circulating tumor cells\", \"cell-free DNA\", \"cfDNA\", \"circulating tumor DNA\", \"ctDNA\", \"tumor fraction\", \"RB1 mutation\" and \"SNCA\". Additionally, historic articles on the advent of liquid biopsy in medicine were also reviewed. Pertinent cross-references from the studies were reviewed. Retrospective interventional and observational case series, observational case series, prospective cohort studies, reviews, case reports, surgical techniques, invited commentary and letters were included.
UNASSIGNED: A total of 40 relevant articles were selected. Biomarkers in aqueous humor, serum and cerebrospinal fluid and their clinical applications are discussed.
UNASSIGNED: Harvesting aqueous humor from eyes with retinoblastoma has been found safe and superior to blood for the detection of chromosomal changes. cfDNA from aqueous can be a surrogate marker to detect somatic copy number alterations and other genetic alterations in RB. ctDNA in plasma also has potential to help in diagnosis and prognosis of RB. Liquid biopsy in RB is an emerging topic, which could pave way for a better understanding of mechanisms for treatment response, resistance and recurrence in RB as well as possibly provide specific therapeutic targets to improve globe salvage.