Comparative analysis of human tear fluid and aqueous humor proteomes.

PURPOSE: Technological advancements allowing for the analysis of low-volume samples have led to the investigation of human tear fluid and aqueous humor (AH) as potential biomarker sources. However, acquiring AH samples poses significant challenges, making human tear fluid a more accessible alternative. This study aims to compare the protein compositions of these two biofluids to evaluate their suitability for biomarker discovery. METHODS: Paired tear and AH samples were collected from 20 patients undergoing cataract surgery. Tear samples were collected using Schirmer strips prior to surgery, and AH samples were collected from the anterior chamber immediately after corneal incision. Proteins were extracted and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 481 proteins were identified in greater than 50% of the tear samples, and 191 proteins were detected in greater than 50% of the AH samples. Of these proteins, 82 were found to be common between the two biofluids, with ALB, LTF, TF, LCN1, and IGKC being the most abundant. CONCLUSION: Although tear fluid and the AH are functionally independent and physically separated, many of the proteins detected in AH were also detected in tears. This direct comparison of the proteomic content of tear fluid and AH may aid in further investigation of tear fluid as a source of readily accessible biomarkers for various human diseases.

Swiss Multicenter Ab Interno XEN45 Gel Stent Study: 2-Year Real-World Data.

INTRODUCTION: The aim of this study was to investigate the 2-year postoperative efficacy of the XEN45 Gel Stent by evaluating the reduction of intraocular pressure (IOP) and the need for eye pressure-lowering medications in a multicenter setting in Switzerland. METHODS: Patients with various types of glaucoma who received a XEN45 Gel Stent with or without combined phacoemulsification cataract surgery at five hospitals in Switzerland were retrospectively enrolled. Pre- and postoperative IOP, the number of antiglaucoma medications, and the need of subsequent interventions to control IOP were assessed. The success rate was defined as a ≥ 20% reduction of IOP 2 years postoperatively without the need for subsequent glaucoma surgery. RESULTS: A total of 345 eyes were included: 44.3% with primary open-angle, 42.0% pseudoexfoliation, and 13.7% with other types of glaucoma. Of these, 206 patients were followed for 2 years. Preoperatively, the mean IOP was 26.3 ± 8.9 mmHg and the mean number of antiglaucoma medications administered was 3.0 ± 1.3. Two years postoperatively, the success rate was 66.0% (95% confidence interval 59.3-72.1%), the IOP had dropped by 43.8% to 14.8 ± 5.7 mmHg, and the number of medications was reduced by a mean of 2.0 ± 1.7 per day. Postoperative complications and the need for interventions remained low. CONCLUSION: The XEN45 Gel Stent successfully reduced IOP and the number of antiglaucoma drugs in most patients at 2 years postoperatively.

AHP DB: a reference database of proteins in the human aqueous humor.

The aqueous humor (AH) is a low-viscosity biofluid that continuously circulates from the posterior chamber to the anterior chamber of the eye. Recent advances in high-resolution mass-spectrometry workflows have facilitated the study of proteomic content in small-volume biofluids like AH, highlighting the potential clinical implications of the AH proteome. Nevertheless, in-depth investigations into the role of AH proteins in ocular diseases have encountered challenges due to limited accessibility to these workflows, difficulties in large-scale AH sample collection and the absence of a reference AH proteomic database. In response to these obstacles, and to promote further research on the involvement of AH proteins in ocular physiology and pathology, we have developed the web-based Aqueous Humor Proteomics Database (AHP DB). The current version of AHP DB contains proteomic data from 307 human AH samples, which were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The database offers comprehensive information on 1683 proteins identified in the AH samples. Furthermore, relevant clinical data are provided for each analyzed sample. Researchers also have the option to download these datasets individually for offline use, rendering it a valuable resource for the scientific community. Database URL: https://ahp.augusta.edu/.

Minimally Invasive Glaucoma Surgery: Latest Developments and Future Challenges.

The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.

Complement System Proteins in the Human Aqueous Humor and Their Association with Primary Open-Angle Glaucoma.

This study discovers the complement protein profile in the aqueous humor (AH) of human subjects and investigates its association with primary open-angle glaucoma (POAG) pathogenesis. Among the 32 complement proteins identified, 22 were highly abundant and detected in more than 50% of AH samples. The most predominant active complement proteins in the AH are C3, C4B, C4A, CFB, CFD, and C9. Additionally, the most prevalent complement regulators and receptors include CLU, SERPING1, F2, CFH, CFI, and VTN. Significant alterations in complement proteins were observed in individuals with POAG compared to those with cataracts. Specifically, complement protein F2 was upregulated, while C8G, C6, and CFH were downregulated in POAG samples. Stratification of the samples by race and sex revealed distinct alterations of complement proteins in patients with POAG. In the African American cohort, five complement proteins (C4A, C4B, F2, C7, and C3) were upregulated in POAG compared to cataract patients. In the Caucasian cohort, eight complement proteins (C3, SERPING1, CFI, CLU, CFHR1, C8G, C6, and CFH) were downregulated in the POAG samples compared to the cataract samples. Within the male cohort, three complement proteins (CLU, C6, and CFH) were downregulated in POAG patients compared to those with cataracts. Whereas, within the female cohort, two complement proteins (C4B and F2) were upregulated and one (C8G) downregulated in the POAG samples when compared to cataracts. Discerning these changes in the AH complement protein profile will assist in the development of tailored therapies to modulate the complement system for managing ocular disorders. These insights may also lead to novel biomarkers for diagnosing and monitoring disease progression.

Follow-up studies of the classical landmark studies in Glaucoma.

PURPOSE OF REVIEW: It was not until the nineteen nineties that there was scientific evidence for the primary treatment concept of glaucoma, lowering intraocular pressure. The treatment concept of lowering intraocular pressure is now proven by randomized controlled clinical trials (landmark studies). This review provides an overview of the follow-up studies to these landmark studies from the last 18 months. RECENT FINDINGS: The 20-year data of the ocular hypertension treatment study showed a 49% incidence of primary open-angle glaucoma. The data of this landmark study was used for developing different machine learning algorithms. Bilateral disease, disc hemorrhages, and higher intraocular pressure (IOP) were risk factors for visual field deterioration in the United Kingdom Glaucoma Treatment Study. The Advanced Glaucoma Intervention Trial and the Collaborative Initial Glaucoma Treatment Study identified demographic factors, comorbidity, and clinical variables associated with visual field damage. Analysis was performed on Chinese subsets from the Laser in Glaucoma and Ocular Hypertension Study (LiGHT). Looking at all the follow-up studies to the tube shunt landmark studies, preoperative IOP, neovascular glaucoma, Ahmed implantation, and younger age were predictors of failure. A follow-up study to the Effectiveness in Angle-Closure Glaucoma in Lens Extraction Study showed that patients were ten times more likely to maintain a drop-free target IOP after lens extraction than after laser iridotomy. A superior location for iridotomy results in significantly more significant angle widening than temporal or nasal locations, as shown by a follow-up study to the Zhongshan Angle Closure Prevention Trial using OCT and gonioscopy. SUMMARY: The number of published follow-up studies to the landmark studies in glaucoma show the ongoing development of clinical questions in management of glaucoma.

Evidence-Based Consensus Guidelines Series for MicroPulse Transscleral Laser Therapy - Surgical Technique, Post-Operative Care, Expected Outcomes and Retreatment/Enhancements.

Purpose: To provide expert consensus and evidence-based current guidelines on treatment technique, postoperative care, expected outcomes and retreatment for MicroPulse Transscleral Laser Treatment (TLT). Methods: A comprehensive search of PubMed led to the identification and analysis of 61 studies on MicroPulse TLT. To provide guidance in areas where there was not enough available literature, a three-round Delphi method was conducted involving 10 international experts in MicroPulse TLT. Results: The response rate was 70% in the first round, 70% in the second round, and 80% in the third round of the Delphi method. Once all responses were aggregated, a live meeting was held with 90% attendance, and consensus was achieved on each of the findings detailed in this manuscript. Conclusion: Used within appropriate treatment parameters, with proper technique and patient selection, MicroPulse TLT is a safe and effective treatment for many types and severities of glaucoma. MicroPulse TLT represents a useful addition to the glaucoma armamentarium.

Topical Anesthesia Offers Sufficient Pain Control for MicroPulse Transscleral Laser Therapy for Glaucoma.

Introduction: The aim of this study was to evaluate patient pain during and after MicroPulse Transscleral Laser Therapy (TLT) and vision-related quality of life using two different anesthesia protocols: "Topical Plus" anesthesia without standby anesthesia (study group), and analgosedation with standby anesthesia (control group). Methods: A retrospective, comparative chart review was conducted to evaluate patient pain between the two groups based on an analog pain scale at baseline and postoperatively (1 hour, 6 hours, 1 day, 1 week, and 1 month). Furthermore, vision-related quality of life at baseline was compared at 1 month postoperatively. Results: Four eyes underwent MicroPulse TLT under Topical Plus anesthesia and 4 eyes underwent analgosedation. The mean age at the time of the MicroPulse TLT was 78.3 ± 6.4 years. In the study group, the reported pain level increased significantly immediately after the treatment (from 0.5 to 2.8, p=0.003; mild pain); however, no difference was found at any later time point compared to baseline. The vision-related quality of life was similar in both groups and was not negatively impacted by the MicroPulse TLT at 1 month after the treatment. Discussion/Conclusion. The Topical Plus anesthesia protocol provides adequate pain control for the patient to remain comfortable during and post-MicroPulse TLT treatment, with no changes in vision-related quality of life. Although the sample size was small and, thus, the results cannot be generalized, this case series showed that it is possible to perform MicroPulse TLT under topical anesthesia.

[Angle-closure glaucoma]. / Winkelblockglaukome.

Angle-closure glaucoma is a rare form of glaucoma characterized by a narrow or an occlusion of the anterior chamber angle and subsequently an obstruction of the outflow of aqueous humor resulting in an increase in intraocular pressure. Symptoms can include severe eye pain and/or headache, blurred vision, a medium-sized and rigid pupil, conjunctival hyperemia, and nausea. Treatment options include pressure-lowering topical and systemic medications as well as surgical interventions, especially cataract surgery and laser iridotomy. Besides parasympathomimetics (pilocarpine), all topical antiglaucoma medications can principally be used (beta-receptor antagonists, carbonic anhydrase inhibitors, alpha­2 selective adrenergic antagonists, prostaglandins and prostaglandin analogues). Carbonic anhydrase inhibitors and osmotic agents (e.g., mannitol) can be systemically used.

Expert Consensus on the Use of the PRESERFLO™ MicroShunt Device in the Treatment of Glaucoma: A Modified Delphi Panel.

INTRODUCTION: The implantation of the PRESERFLO™ MicroShunt (PMS) device has been shown to significantly lower increased intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG). However, guidelines on best practice for patient selection and pre-/peri-/postoperative care management are lacking. The aim of this modified Delphi panel was to achieve expert consensus on the role of the PMS to treat patients with glaucoma in Europe. METHODS: Twelve European glaucoma surgeons experienced with the PMS procedure participated in a three-round modified Delphi panel. A targeted literature review and expert steering committee guided round 1 questionnaire development. Consensus was set at a pre-defined threshold of at least 70% of panellists selecting 'Strongly disagree'/'Disagree' or 'Strongly agree'/'Agree' for six-point Likert scale questions, or at least 70% selecting the same option for multiple-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions. RESULTS: Consensus was achieved for 60.3% (n = 38/63), 60.0% (n = 18/30), and 100.0% (n = 11/11) of Likert/multiple-choice questions in rounds 1, 2, and 3, respectively. There was agreement that the PMS procedure is effective at reducing IOP in patients with high-tension POAG (greater than 21 mmHg). Although surgical techniques may vary slightly, consensus was reached on several points, including the importance of posterior application of mitomycin C (MMC). Panellists agreed that the PMS postoperative follow-up appointment schedule is reasonably predictable and mostly characterised by fewer visits than with trabeculectomy, particularly in the early phase. Although panellists agreed that combined cataract/PMS surgery and the use of non-MMC wound-healing modulators/antifibrotics during the procedure are possible, further data are needed to determine efficacy. CONCLUSION: The expert consensus reached in this panel will help inform best practice guidelines in the treatment of patients with glaucoma in Europe. Panellists also highlighted key areas for future research to improve understanding of the PMS in the treatment algorithm of glaucoma.

Evidence-Based Consensus Guidelines Series for MicroPulse Transscleral Laser Therapy: Dosimetry and Patient Selection.

Purpose: To provide consensus-based current guidelines on optimal dosimetry and patient selection for MicroPulse Transscleral Laser Therapy (TLT) based on a review of the literature and a Delphi method. Methods: A comprehensive search of Pub Med led to the identification and analysis of 61 studies on MicroPulse TLT that contained information on laser settings and patient selection. To determine consensus in areas where there was not enough available literature, a three-round Delphi method was conducted. Results: The response rate was 90% in the first round, 90% in the second round, and 80% in the third round of the Delphi technique. Once all responses were aggregated, a live meeting was held with 80% attendance, and consensus was achieved on each of the findings detailed in this manuscript. Conclusion: Micropulse TLT is a useful addition to the glaucoma armamentarium. When used with proper surgical technique at energy settings within the boundaries described in this manuscript, MicroPulse TLT is a safe and effective treatment for many types and stages of glaucoma. Based on current knowledge and experience, the consensus recommendation of this expert panel is that the standard MicroPulse TLT settings using the revised MicroPulse P3 Probe should be 2500 mW, 31.3% duty cycle, and 4 sweeps at a sweep velocity of 20 seconds each per hemisphere. Both hemispheres avoiding the 3 and 9 clock hours should be treated. The panel also reached consensus on patient selection for MicroPulse TLT providing guidance for the use of the procedure.

Selective laser trabeculoplasty following failed combined phacoemulsification cataract extraction and excimer laser trabeculotomy can control intraocular pressure for a limited time.

PURPOSE: To assess the efficacy of selective laser trabeculoplasty (SLT) following failed phacoemulsification cataract extraction combined with excimer laser trabeculotomy (phaco-ELT). METHODS: Retrospectively, the medical records of patients with primary or secondary open-angle glaucoma or ocular hypertension who underwent SLT between January 2001 and February 2015 by one surgeon at a single center after a failed phaco-ELT were evaluated. Exclusion criteria were: angle-closure glaucoma, optic nerve atrophy due to disease other than glaucoma, and additional glaucoma procedures between phaco-ELT and SLT. The main outcome measures were time to failure and Kaplan-Meier survival. Complete success was defined as a reduction of intraocular pressure (IOP) of > 3 mmHg and > 20% compared to baseline, and the number of AGM ≤ baseline. RESULTS: A total of 23 eyes of 21 subjects were included. Baseline IOP was 19.7 (range, 19.1-22.7) mmHg, and the number of AGM at baseline was 2.5 (range, 1.9-2.9). Median time to failure after SLT was 7.2 (range, 6.6-7.8) months. The number of antiglaucoma medications did not change during that time. CONCLUSIONS: In eyes in which the IOP is no longer controlled following phaco-ELT, SLT could be an option to slow disease progression or prolong time until incisional filtration surgery. However, time to failure after SLT is limited. Thus, close follow-up visits are necessary in order to not delay an incisional surgery.

First and second transscleral cyclophotocoagulation treatments provide similar intraocular pressure-lowering efficacy in patients with refractory glaucoma.

PURPOSE: The aim of this study is to address the safety and effectiveness of a second continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) treatment by comparing its outcome against a first CW-TSCPC treatment in the same patients with refractory glaucoma. METHODS: Twenty-one eyes with either primary or secondary glaucoma received a second CW-TSCPC laser session ≥ 3 months after the first treatment. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of topical or oral ophthalmic pressure-reducing medications were registered at every time point up to the last follow-up at 3 months. A complete slit-lamp examination was conducted to record for complications or other abnormal ocular findings. Success was defined as IOP between 6 and 21 mmHg and > 20% reduction in IOP with or without anti-glaucoma medications. RESULTS: At 3 months follow-up of the first CW-TSCPC treatment, a 24.8% decrease in IOP was observed, whereas a 45.6% IOP decrease was observed 3 months post the second CW-TSCPC treatment. Visual acuity did not decrease, and no major complications were observed post either treatment within the follow-up period. Time to failure was 79.5 ± 24.6 and 77.1 ± 29.4, respectively (P = 0.955). No serious complications were observed. CONCLUSION: A second CW-TSCPC treatment proved to be a safe and effective treatment option when the first CW-TSCPC treatment was insufficient in maintaining the desired IOP level for a prolonged time (mean time between both sessions 6.4 ± 8.0 months).

The AIDA and the extra laser systems for excimer laser trabeculotomy proved comparable IOP lowering efficacy-12-month results.

PURPOSE: Cataract surgery combined with excimer laser trabeculotomy (phaco-ELT) leads to a significant reduction in intraocular pressure by enhancing trabecular outflow. The aim of this study is to compare two laser systems for ELT (AIDA vs. ExTra). METHODS: In this retrospective chart review, inclusion criteria were a diagnosis of glaucoma and phaco-ELT between 07/17/2010 and 07/17/2018. Data were collected preoperatively and postoperatively up to 1 year. Success was defined as IOP reduction of ≥ 20% compared to baseline plus an IOP of < 21 mmHg with no hypotony, no loss of light perception vision, and no subsequent glaucoma surgery. RESULTS: Three hundred and fourteen eyes (mean age 75.9 ± 8.6 years) were included. Baseline intraocular pressure (IOP) for the ExTra group (94 eyes) was 20.3 ± 5.9 mmHg on 2.0 ± 1.3 anti-glaucoma drugs (AGD) and a best-corrected visual acuity (BCVA, logMar) of 0.5 ± 0.4. For The AIDA group (220 eyes), baseline IOP was 18.7 ± 6.3 mmHg on 2.0 ± 1.3 AGD and a BCVA of 0.3 ± 0.3. In the ExTra group, IOP was reduced to 12.8 ± 2.5 mmHg (-37%) and in the AIDA group to 14.7 ± 3.9 (-21%, p = 0.14) at 1 year. AGD reduction in the ExTra group was 1.3 ± 1.5 and 1.8 ± 1.4 in the AIDA group (p = 0.14). Success rates were 80% (ExTra) and 70% (AIDA), respectively (p = 0.552). Thirty-one eyes (10.0%) required a subsequent glaucoma surgery during the follow-up. CONCLUSION: Both laser platforms, the ExTra and the AIDA laser, used for Phaco-ELT lead to a significant reduction in intraocular pressure and anti-glaucoma drugs with no statistically significant difference in success rates during the follow-up of 12 months. TRIAL REGISTRATION SWISSETHICS: 2018-01,791.

MicroPulse Transscleral Laser Therapy Demonstrates Similar Efficacy with a Superior and More Favorable Safety Profile Compared to Continuous-Wave Transscleral Cyclophotocoagulation.

PURPOSE: The aim of this study was to compare effectiveness and safety of MicroPulse transscleral laser therapy (MP-TLT) using the original MicroPulse P3® device and continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) using the G-Probe® device in glaucoma. METHODS: Spherical equivalent, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of topical or oral ophthalmic pressure-reducing medications were registered at every time point, up to the last follow-up at 12 months. A complete slit-lamp examination was conducted to record the following complications: corneal edema, persistent ocular hypotony (IOP ≤5 mmHg) on two consecutive follow-up visits, choroidal detachment, phthisis bulbi, sympathetic ophthalmia, cystoid macular edema, or other abnormal ocular findings. Success was defined as IOP between 6 and 21 mmHg and >20% reduction in IOP with or without antiglaucoma medications. RESULTS: 47 eyes underwent MP-TLT and 150 CW-TSCPC. At 12 months, success was achieved in 88.6% in the CW-TSCPC group and 87.5% in the MP-TLT group (p = 0.883). In the CW-TSCPC group, eyes achieved a 42.4% IOP reduction (from 28.3 ± 12.3 mmHg to 15.3 ± 6.0 mmHg) and a 31.1% reduction (from 22.0 ± 7.2 mmHg to 15.7 ± 4.8 mmHg) in the MP-TLT group. Visual acuity remained primarily unaltered in both groups. CONCLUSION: MP-TLT was as effective in lowering IOP as CW-TSCPC and achieved comparable success. Additionally, MP-TLT demonstrated consistent and effective outcomes at every time point. The improved safety profile of MP-TLT allows the therapeutic spectrum to be broadened, granting ophthalmologists' treatment of glaucoma in earlier stages of glaucoma than those typically treated with CW-TSCPC, i.e., early to moderate and to patients with good central-vision.