Research

16 pages, 2629 KiB

Open AccessArticle

Using Fused Data from Perimetry and Optical Coherence Tomography to Improve the Detection of Visual Field Progression in Glaucoma

by Leo Yan Li-Han, Moshe Eizenman, Runjie Bill Shi, Yvonne M. Buys, Graham E. Trope and Willy Wong

Bioengineering 2024, 11(3), 250; https://doi.org/10.3390/bioengineering11030250 - 03 Mar 2024

Viewed by 752

Abstract

Perimetry and optical coherence tomography (OCT) are both used to monitor glaucoma progression. However, combining these modalities can be a challenge due to differences in data types. To overcome this, we have developed an autoencoder data fusion (AEDF) model to learn compact encoding [...] Read more.

Perimetry and optical coherence tomography (OCT) are both used to monitor glaucoma progression. However, combining these modalities can be a challenge due to differences in data types. To overcome this, we have developed an autoencoder data fusion (AEDF) model to learn compact encoding (AE-fused data) from both perimetry and OCT. The AEDF model, optimized specifically for visual field (VF) progression detection, incorporates an encoding loss to ensure the interpretation of the AE-fused data is similar to VF data while capturing key features from OCT measurements. For model training and evaluation, our study included 2504 longitudinal VF and OCT tests from 140 glaucoma patients. VF progression was determined from linear regression slopes of longitudinal mean deviations. Progression detection with AE-fused data was compared to VF-only data (standard clinical method) as well as data from a Bayesian linear regression (BLR) model. In the initial 2-year follow-up period, AE-fused data achieved a detection F1 score of 0.60 (95% CI: 0.57 to 0.62), significantly outperforming (p < 0.001) the clinical method (0.45, 95% CI: 0.43 to 0.47) and the BLR model (0.48, 95% CI: 0.45 to 0.51). The capacity of the AEDF model to generate clinically interpretable fused data that improves VF progression detection makes it a promising data integration tool in glaucoma management. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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15 pages, 4503 KiB

Open AccessArticle

Development and Verification of a Novel Three-Dimensional Aqueous Outflow Model for High-Throughput Drug Screening

by Matthew Fung, James J. Armstrong, Richard Zhang, Anastasiya Vinokurtseva, Hong Liu and Cindy Hutnik

Bioengineering 2024, 11(2), 142; https://doi.org/10.3390/bioengineering11020142 - 31 Jan 2024

Viewed by 793

Abstract

Distal outflow bleb-forming procedures in ophthalmic surgery expose subconjunctival tissue to inflammatory cytokines present in the aqueous humor, resulting in impaired outflow and, consequently, increased intraocular pressure. Clinically, this manifests as an increased risk of surgical failure often necessitating revision. This study (1) [...] Read more.

Distal outflow bleb-forming procedures in ophthalmic surgery expose subconjunctival tissue to inflammatory cytokines present in the aqueous humor, resulting in impaired outflow and, consequently, increased intraocular pressure. Clinically, this manifests as an increased risk of surgical failure often necessitating revision. This study (1) introduces a novel high-throughput screening platform for testing potential anti-fibrotic compounds and (2) assesses the clinical viability of modulating the transforming growth factor beta-SMAD2/3 pathway as a key contributor to post-operative outflow reduction, using the signal transduction inhibitor verteporfin. Human Tenon’s capsule fibroblasts (HTCFs) were cultured within a 3D collagen matrix in a microfluidic system modelling aqueous humor drainage. The perfusate was augmented with transforming growth factor beta 1 (TGFβ1), and afferent pressure to the tissue-mimetic was continuously monitored to detect treatment-related pressure elevations. Co-treatment with verteporfin was employed to evaluate its capacity to counteract TGFβ1 induced pressure changes. Immunofluorescent studies were conducted on the tissue-mimetic to corroborate the pressure data with cellular changes. Introduction of TGFβ1 induced treatment-related afferent pressure increase in the tissue-mimetic. HTCFs treated with TGFβ1 displayed visibly enlarged cytoskeletons and stress fiber formation, consistent with myofibroblast transformation. Importantly, verteporfin effectively mitigated these changes, reducing both afferent pressure increases and cytoskeletal alterations. In summary, this study models the pathological filtration bleb response to TGFβ1, while demonstrating verteporfin’s effectiveness in ameliorating both functional and cellular changes caused by TGFβ1. These demonstrate modulation of the aforementioned pathway as a potential avenue for addressing post-operative changes and reductions in filtration bleb outflow capacity. Furthermore, the establishment of a high-throughput screening platform offers a valuable pre-animal testing tool for investigating potential compounds to facilitate surgical wound healing. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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13 pages, 2673 KiB

Open AccessArticle

Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data

by Mark Christopher, Ruben Gonzalez, Justin Huynh, Evan Walker, Bharanidharan Radha Saseendrakumar, Christopher Bowd, Akram Belghith, Michael H. Goldbaum, Massimo A. Fazio, Christopher A. Girkin, Carlos Gustavo De Moraes, Jeffrey M. Liebmann, Robert N. Weinreb, Sally L. Baxter and Linda M. Zangwill

Bioengineering 2024, 11(2), 140; https://doi.org/10.3390/bioengineering11020140 - 30 Jan 2024

Viewed by 906

Abstract

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery [...] Read more.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging. The ML models were trained to predict surgical interventions and evaluated on independent data collected at a separate study site. The models were evaluated based on their ability to predict surgeries at varying lengths of time prior to surgical intervention. The highest performing predictions achieved an AUC of 0.93, 0.92, and 0.93 in predicting surgical intervention at 1 year, 2 years, and 3 years, respectively. The models were also able to achieve high sensitivity (0.89, 0.77, 0.86 at 1, 2, and 3 years, respectively) and specificity (0.85, 0.90, and 0.91 at 1, 2, and 3 years, respectively) at an 0.80 level of precision. The multi-modal models trained on a combination of data types predicted surgical interventions with high accuracy up to three years prior to surgery and could provide an important tool to predict the need for glaucoma intervention. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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13 pages, 5038 KiB

Open AccessArticle

Swept-Source Anterior Segment Optical Coherence Tomography Imaging and Quantification of Bleb Parameters in Glaucoma Filtration Surgery

by Jeremy C.K. Tan, Hussameddin Muntasser, Anshoo Choudhary, Mark Batterbury and Neeru A. Vallabh

Bioengineering 2023, 10(10), 1186; https://doi.org/10.3390/bioengineering10101186 - 13 Oct 2023

Cited by 1 | Viewed by 1169

Abstract

This paper describes a technique for using swept-source anterior segment optical coherence tomography (AS-OCT) to visualize internal bleb microstructure and objectively quantify dimensions of the scleral flap and trabeculo-Descemet window (TDW) in non-penetrating glaucoma filtration surgery (GFS). This was a cross-sectional study of [...] Read more.

This paper describes a technique for using swept-source anterior segment optical coherence tomography (AS-OCT) to visualize internal bleb microstructure and objectively quantify dimensions of the scleral flap and trabeculo-Descemet window (TDW) in non-penetrating glaucoma filtration surgery (GFS). This was a cross-sectional study of 107 filtering blebs of 67 patients who had undergone deep sclerectomy surgery at least 12 months prior. The mean post-operative follow-up duration was 6.5 years +/− 4.1 [standard deviation (SD)]. The maximal bleb height was significantly greater in the complete success (CS) blebs compared to the qualified success (QS) and failed (F) blebs (1.48 vs. 1.17 vs. 1.10 mm in CS vs. QS vs. F, one-way ANOVA, p < 0.0001). In a subcohort of deep sclerectomy blebs augmented by intraoperative Mitomycin-C, the trabeculo-Descemet window was significantly longer in the complete success compared to the qualified success group (613.7 vs. 378.1 vs. 450.8 µm in CS vs. QS vs. F, p = 0.004). The scleral flap length, thickness, and width were otherwise similar across the three outcome groups. The quantification of surgical parameters that influence aqueous outflow in non-penetrating GFS can help surgeons better understand the influence of these structures on aqueous outflow and improve surgical outcomes. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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27 pages, 9882 KiB

Open AccessArticle

Exploring New Therapeutic Avenues for Ophthalmic Disorders: Glaucoma-Related Molecular Docking Evaluation and Bibliometric Analysis for Improved Management of Ocular Diseases

by Flaviu Bodea, Simona Gabriela Bungau, Andrei Paul Negru, Ada Radu, Alexandra Georgiana Tarce, Delia Mirela Tit, Alexa Florina Bungau, Cristian Bustea, Tapan Behl and Andrei-Flavius Radu

Bioengineering 2023, 10(8), 983; https://doi.org/10.3390/bioengineering10080983 - 20 Aug 2023

Cited by 4 | Viewed by 1173

Abstract

Ophthalmic disorders consist of a broad spectrum of ailments that impact the structures and functions of the eye. Due to the crucial function of the retina in the vision process, the management of eye ailments is of the utmost importance, but several unmet [...] Read more.

Ophthalmic disorders consist of a broad spectrum of ailments that impact the structures and functions of the eye. Due to the crucial function of the retina in the vision process, the management of eye ailments is of the utmost importance, but several unmet needs have been identified in terms of the outcome measures in clinical trials, more proven minimally invasive glaucoma surgery, and a lack of comprehensive bibliometric assessments, among others. The current evaluation seeks to fulfill several of these unmet needs via a dual approach consisting of a molecular docking analysis based on the potential of ripasudil and fasudil to inhibit Rho-associated protein kinases (ROCKs), virtual screening of ligands, and pharmacokinetic predictions, emphasizing the identification of new compounds potentially active in the management of glaucoma, and a comprehensive bibliometric analysis of the most recent publications indexed in the Web of Science evaluating the management of several of the most common eye conditions. This method resulted in the finding of ligands (i.e., ZINC000000022706 with the most elevated binding potential for ROCK1 and ZINC000034800307 in the case of ROCK2) that are not presently utilized in any therapeutic regimen but may represent a future option to be successfully applied in the therapeutic scheme of glaucoma following further comprehensive testing validations. In addition, this research also analyzed multiple papers listed in the Web of Science collection of databases via the VOSviewer application to deliver, through descriptive analysis of the results, an in-depth overview of publications contributing to the present level of comprehension in therapeutic approaches to ocular diseases in terms of scientific impact, citation analyses, most productive authors, journals, and countries, as well as collaborative networks. Based on the molecular docking study’s preliminary findings, the most promising candidates must be thoroughly studied to determine their efficacy and risk profiles. Bibliometric analysis may also help researchers set targets to improve ocular disease outcomes. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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Review

Jump to: Research, Other

18 pages, 3412 KiB

Open AccessReview

Advances and Challenges in Wearable Glaucoma Diagnostics and Therapeutics

by Ryan Shean, Ning Yu, Sourish Guntipally, Van Nguyen, Ximin He, Sidi Duan, Kimberly Gokoffski, Yangzhi Zhu and Benjamin Xu

Bioengineering 2024, 11(2), 138; https://doi.org/10.3390/bioengineering11020138 - 30 Jan 2024

Cited by 1 | Viewed by 1090

Abstract

Glaucoma is a leading cause of irreversible blindness, and early detection and treatment are crucial for preventing vision loss. This review aims to provide an overview of current diagnostic and treatment standards, recent medical and technological advances, and current challenges and future outlook [...] Read more.

Glaucoma is a leading cause of irreversible blindness, and early detection and treatment are crucial for preventing vision loss. This review aims to provide an overview of current diagnostic and treatment standards, recent medical and technological advances, and current challenges and future outlook for wearable glaucoma diagnostics and therapeutics. Conventional diagnostic techniques, including the rebound tonometer and Goldmann Applanation Tonometer, provide reliable intraocular pressure (IOP) measurement data at single-interval visits. The Sensimed Triggerfish and other emerging contact lenses provide continuous IOP tracking, which can improve diagnostic IOP monitoring for glaucoma. Conventional therapeutic techniques include eye drops and laser therapies, while emerging drug-eluting contact lenses can solve patient noncompliance with eye medications. Theranostic platforms combine diagnostic and therapeutic capabilities into a single device. Advantages of these platforms include real-time monitoring and personalized medication dosing. While there are many challenges to the development of wearable glaucoma diagnostics and therapeutics, wearable technologies hold great potential for enhancing glaucoma management by providing continuous monitoring, improving medication adherence, and reducing the disease burden on patients and healthcare systems. Further research and development of these technologies will be essential to optimizing patient outcomes. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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12 pages, 1076 KiB

Open AccessReview

Addressing Glaucoma in Myopic Eyes: Diagnostic and Surgical Challenges

by Kateki Vinod and Sarwat Salim

Bioengineering 2023, 10(11), 1260; https://doi.org/10.3390/bioengineering10111260 - 29 Oct 2023

Viewed by 1114

Abstract

Epidemiological and genetic studies provide strong evidence supporting an association between myopia and glaucoma. The accurate detection of glaucoma in myopic eyes, especially those with high myopia, remains clinically challenging due to characteristic morphologic features of the myopic optic nerve in addition to [...] Read more.

Epidemiological and genetic studies provide strong evidence supporting an association between myopia and glaucoma. The accurate detection of glaucoma in myopic eyes, especially those with high myopia, remains clinically challenging due to characteristic morphologic features of the myopic optic nerve in addition to limitations of current optic nerve imaging modalities. Distinguishing glaucoma from myopia is further complicated by overlapping perimetric findings. Therefore, longitudinal follow-up is essential to differentiate progressive structural and functional abnormalities indicative of glaucoma from defects that may result from myopia alone. Highly myopic eyes are at increased risk of complications from traditional incisional glaucoma surgery and may benefit from newer microinvasive glaucoma surgeries in select cases. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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26 pages, 1095 KiB

Open AccessReview

Corneal Biomechanical Measures for Glaucoma: A Clinical Approach

by Abdelrahman M. Elhusseiny, Giuliano Scarcelli and Osamah J. Saeedi

Bioengineering 2023, 10(10), 1108; https://doi.org/10.3390/bioengineering10101108 - 22 Sep 2023

Viewed by 1077

Abstract

Over the last two decades, there has been growing interest in assessing corneal biomechanics in different diseases, such as keratoconus, glaucoma, and corneal disorders. Given the interaction and structural continuity between the cornea and sclera, evaluating corneal biomechanics may give us further insights [...] Read more.

Over the last two decades, there has been growing interest in assessing corneal biomechanics in different diseases, such as keratoconus, glaucoma, and corneal disorders. Given the interaction and structural continuity between the cornea and sclera, evaluating corneal biomechanics may give us further insights into the pathogenesis, diagnosis, progression, and management of glaucoma. Therefore, some authorities have recommended baseline evaluations of corneal biomechanics in all glaucoma and glaucoma suspects patients. Currently, two devices (Ocular Response Analyzer and Corneal Visualization Schiempflug Technology) are commercially available for evaluating corneal biomechanics; however, each device reports different parameters, and there is a weak to moderate agreement between the reported parameters. Studies are further limited by the inclusion of glaucoma subjects taking topical prostaglandin analogues, which may alter corneal biomechanics and contribute to contradicting results, lack of proper stratification of patients, and misinterpretation of the results based on factors that are confounded by intraocular pressure changes. This review aims to summarize the recent evidence on corneal biomechanics in glaucoma patients and insights for future studies to address the current limitations of the literature studying corneal biomechanics. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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27 pages, 3159 KiB

Open AccessReview

Recent Advancements in Glaucoma Surgery—A Review

by Bryan Chin Hou Ang, Sheng Yang Lim, Bjorn Kaijun Betzler, Hon Jen Wong, Michael W. Stewart and Syril Dorairaj

Bioengineering 2023, 10(9), 1096; https://doi.org/10.3390/bioengineering10091096 - 19 Sep 2023

Cited by 1 | Viewed by 2236

Abstract

Surgery has long been an important treatment for limiting optic nerve damage and minimising visual loss in patients with glaucoma. Numerous improvements, modifications, and innovations in glaucoma surgery over recent decades have improved surgical safety, and have led to earlier and more frequent [...] Read more.

Surgery has long been an important treatment for limiting optic nerve damage and minimising visual loss in patients with glaucoma. Numerous improvements, modifications, and innovations in glaucoma surgery over recent decades have improved surgical safety, and have led to earlier and more frequent surgical intervention in glaucoma patients at risk of vision loss. This review summarises the latest advancements in trabeculectomy surgery, glaucoma drainage device (GDD) implantation, and minimally invasive glaucoma surgery (MIGS). A comprehensive search of MEDLINE, EMBASE, and CENTRAL databases, alongside subsequent hand searches—limited to the past 10 years for trabeculectomy and GDDs, and the past 5 years for MIGS—yielded 2283 results, 58 of which were included in the final review (8 trabeculectomy, 27 GDD, and 23 MIGS). Advancements in trabeculectomy are described in terms of adjunctive incisions, Tenon’s layer management, and novel suturing techniques. Advancements in GDD implantation pertain to modifications of surgical techniques and devices, novel methods to deal with postoperative complications and surgical failure, and the invention of new GDDs. Finally, the popularity of MIGS has recently promoted modifications to current surgical techniques and the development of novel MIGS devices. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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Other

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13 pages, 1314 KiB

Open AccessBrief Report

Multi-Dataset Comparison of Vision Transformers and Convolutional Neural Networks for Detecting Glaucomatous Optic Neuropathy from Fundus Photographs

by Elizabeth E. Hwang, Dake Chen, Ying Han, Lin Jia and Jing Shan

Bioengineering 2023, 10(11), 1266; https://doi.org/10.3390/bioengineering10111266 - 30 Oct 2023

Viewed by 1046

Abstract

Glaucomatous optic neuropathy (GON) can be diagnosed and monitored using fundus photography, a widely available and low-cost approach already adopted for automated screening of ophthalmic diseases such as diabetic retinopathy. Despite this, the lack of validated early screening approaches remains a major obstacle [...] Read more.

Glaucomatous optic neuropathy (GON) can be diagnosed and monitored using fundus photography, a widely available and low-cost approach already adopted for automated screening of ophthalmic diseases such as diabetic retinopathy. Despite this, the lack of validated early screening approaches remains a major obstacle in the prevention of glaucoma-related blindness. Deep learning models have gained significant interest as potential solutions, as these models offer objective and high-throughput methods for processing image-based medical data. While convolutional neural networks (CNN) have been widely utilized for these purposes, more recent advances in the application of Transformer architectures have led to new models, including Vision Transformer (ViT,) that have shown promise in many domains of image analysis. However, previous comparisons of these two architectures have not sufficiently compared models side-by-side with more than a single dataset, making it unclear which model is more generalizable or performs better in different clinical contexts. Our purpose is to investigate comparable ViT and CNN models tasked with GON detection from fundus photos and highlight their respective strengths and weaknesses. We train CNN and ViT models on six unrelated, publicly available databases and compare their performance using well-established statistics including AUC, sensitivity, and specificity. Our results indicate that ViT models often show superior performance when compared with a similarly trained CNN model, particularly when non-glaucomatous images are over-represented in a given dataset. We discuss the clinical implications of these findings and suggest that ViT can further the development of accurate and scalable GON detection for this leading cause of irreversible blindness worldwide. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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25 pages, 732 KiB

Open AccessSystematic Review

Premium Intraocular Lenses in Glaucoma—A Systematic Review

by Ashley Shuen Ying Hong, Bryan Chin Hou Ang, Emily Dorairaj and Syril Dorairaj

Bioengineering 2023, 10(9), 993; https://doi.org/10.3390/bioengineering10090993 - 22 Aug 2023

Viewed by 1387

Abstract

The incidence of both cataract and glaucoma is increasing globally. With increasing patient expectation and improved technology, premium intraocular lenses (IOLs), including presbyopia-correcting and toric IOLs, are being increasingly implanted today. However, concerns remain regarding the use of premium IOLs, particularly presbyopia-correcting IOLs, [...] Read more.

The incidence of both cataract and glaucoma is increasing globally. With increasing patient expectation and improved technology, premium intraocular lenses (IOLs), including presbyopia-correcting and toric IOLs, are being increasingly implanted today. However, concerns remain regarding the use of premium IOLs, particularly presbyopia-correcting IOLs, in eyes with glaucoma. This systematic review evaluates the use of premium IOLs in glaucoma. A comprehensive search of the MEDLINE database was performed from inception until 1 June 2023. Initial search yielded 1404 records, of which 12 were included in the final review of post-operative outcomes. Studies demonstrated high spectacle independence for distance and good patient satisfaction in glaucomatous eyes, with positive outcomes also in post-operative visual acuity, residual astigmatism, and contrast sensitivity. Considerations in patient selection include anatomical and functional factors, such as the type and severity of glaucomatous visual field defects, glaucoma subtype, presence of ocular surface disease, ocular changes after glaucoma surgery, and the reliability of disease monitoring, all of which may be affected by, or influence, the outcomes of premium IOL implantation in glaucoma patients. Regular reviews on this topic are needed in order to keep up with the rapid advancements in IOL technology and glaucoma surgical treatments. Full article

(This article belongs to the Special Issue Meeting Challenges in the Diagnosis and Treatment of Glaucoma)

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