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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: 15 June 2026 | Viewed by 10293

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Dr. Alessio Martucci

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Guest Editor

Ophthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: glaucoma; clinical research; neuro-ophthalmology; artificial intelligence; ophthalmology; anterior segment

Special Issue Information

Dear Colleagues,

This Special Issue focuses on the latest innovations and emerging strategies in the diagnosis and treatment of glaucoma, a leading cause of irreversible blindness worldwide. With the advent of advanced imaging modalities, such as optical coherence tomography (OCT) and OCT angiography, clinicians are now better equipped to detect glaucoma at its earliest stages. Artificial intelligence and machine learning algorithms are further enhancing diagnostic precision and disease monitoring. On the therapeutic front, the issue highlights novel pharmacologic agents, sustained-release drug delivery systems, and the growing role of minimally invasive glaucoma surgeries (MIGS). It also explores personalized medicine approaches, including genetic profiling, neurodegeneration, and neuroprotective therapies, aimed at preserving vision beyond intraocular pressure control. By bringing together cutting-edge research and clinical perspectives, this issue aims to inform and inspire advancements in glaucoma management, improve patient outcomes, and encourage continued innovation in ophthalmology.

Dr. Alessio Martucci
Guest Editor

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Keywords

OCT
glaucoma
MIGS
neuroprotection
drug delivery systems
artificial intelligence
pharmacologic agents
per-sonalized medicine

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Published Papers (8 papers)

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Research

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10 pages, 1398 KB

Open AccessArticle

Quantitative Ultrasound Biomicroscopy Assessment of Anterior Chamber Angle Changes One Year After Laser Peripheral Iridotomy in Primary Angle Closure Suspects

by Juliette Buffault, Paul Bastelica, Erwan Benouaghrem, Nassima Benhatchi, Christophe Baudouin and Antoine Labbé

J. Clin. Med. 2026, 15(7), 2544; https://doi.org/10.3390/jcm15072544 - 26 Mar 2026

Viewed by 305

Abstract

Background: Laser peripheral iridotomy (LPI) is the first-line treatment for eyes with primary angle closure suspect (PACS), but the extent and durability of anterior chamber angle widening over time remain variable. Ultrasound biomicroscopy (UBM) allows detailed quantitative assessment of angle anatomy and underlying mechanisms of residual angle closure. Methods: In this prospective cohort study, 39 eyes of 20 PACS patients underwent UBM examination before LPI and at 1 month and 1 year post-procedure. Angle opening distance at 500 µm from the scleral spur (AOD500) and trabecular–ciliary process distance (TCPD) were measured in four quadrants under standardized light conditions. Paired comparisons and linear regression analyses were performed. Results: Mean AOD500 increased significantly from baseline (90.1 ± 52.5 µm) to 1 month (146.2 ± 58.2 µm, p < 0.001) and remained greater at 1 year (128.4 ± 48.8 µm, p < 0.001), with the largest changes observed in the superior quadrant. TCPD remained unchanged over time. Despite a patent iridotomy, iridotrabecular contact (ITC) persisted in 12.8% of eyes at 1 year. Plateau iris configuration was identified in 35.9% of eyes. Eyes with smaller baseline AOD500 showed a more limited anatomical response to LPI, although interaction testing did not reach statistical significance. Conclusions: LPI induces significant but partially attenuated anterior chamber angle widening at one year in PACS eyes. A substantial subset exhibits persistent angle closure, frequently associated with plateau iris configuration, underscoring the need for continued post-LPI anatomical surveillance and mechanism-based management. Full article

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

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13 pages, 357 KB

Open AccessFeature PaperArticle

Visual Field Progression in Childhood Glaucoma Versus Open-Angle Glaucoma: A Retrospective Comparative Study

by Ainhoa Colina-Jareno, Ruben Sanchez-Jean, Irene Serrano-Garcia, Julian Garcia-Feijoo and Carmen Mendez-Hernandez

J. Clin. Med. 2026, 15(3), 1146; https://doi.org/10.3390/jcm15031146 - 2 Feb 2026

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Abstract

Background: Evidence on long-term visual field progression in childhood glaucoma compared with open-angle glaucoma (OAG) is limited. We compared the rate and timing of visual field progression and identified predictors of final visual field status. Methods: Single-center, retrospective, observational study including childhood glaucoma and OAG, with ≥3 reliable visual field tests and ≥2 years of follow-up. Visual fields were obtained with Octopus perimeter (Haag-Streit Diagnostics, Köniz, Switzerland) with the G grid and TOP strategy. Visual field progression was evaluated using the rate of change in mean defect (MD, dB/year). Rates were compared with the Mann–Whitney U test. Timing was evaluated with Kaplan–Meier and restricted mean survival time (RMST). Cox models assessed risk of progression. Secondary analysis used multiple linear regression to identify predictors of final MD. The mean follow-up duration was 5.7 ± 2.6 years. Results: 171 eyes (87 childhood glaucoma, 84 OAG) were analyzed. Childhood glaucoma had worse baseline MD (10.7 ± 7.5 dB) than OAG (5.1 ± 6.5 dB, p < 0.001), and underwent more surgeries, while OAG used more medications. The median MD progression rate was −2.3 dB/year [IQR: −5.6 to 0.1] in childhood glaucoma vs. 0.0 dB/year [IQR: −1.2 to 1.3] in OAG (p < 0.001), a value consistent with functional stability under treatment, with some eyes showing negative slopes indicating relative improvement. In Octopus perimetry, MD is expressed on a positive scale, so a negative slope reflects absence of visual field worsening, suggesting comparatively greater deterioration in OAG. Kaplan–Meier curves showed similar progression-free survival between groups (Log-Rank p = 0.284). RMST at 12 years was 10.93 years in childhood glaucoma and 10.56 years in OAG (difference ≈ 4.4 months, not clinically relevant). These survival results should be interpreted cautiously due to the low number of progression events and the high censoring rate. In regression, baseline MD was the strongest predictor of final MD; a higher number of medications was associated with worse final MD; number of surgeries and follow-up duration were not significant predictors. Conclusions: MD slopes suggested faster deterioration in OAG than in childhood glaucoma, whereas the timing to first progression was similar between groups. Baseline differences and treatment patterns were consistent with functional stability in childhood glaucoma under current management strategies. These findings support individualized follow-up and timely intervention, especially in pediatric patients. Full article

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

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10 pages, 782 KB

Open AccessArticle

Development of an Algorithm to Assist in the Diagnosis of Combined Retinal Vein Occlusion and Glaucoma

by Hiroshi Kasai, Kazuyoshi Kitamura, Yuka Hasebe, Junya Mizutani, Kengo Utsunomiya, Shiori Sato, Kohei Murao, Yoichiro Ninomiya, Kensaku Mori, Kazuhide Kawase, Masaki Tanito, Toru Nakazawa, Atsuya Miki, Kazuhiko Mori, Takeshi Yoshitomi and Kenji Kashiwagi

J. Clin. Med. 2025, 14(23), 8547; https://doi.org/10.3390/jcm14238547 - 2 Dec 2025

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Abstract

Objectives: To develop an algorithm to assist in the diagnosis of glaucoma with concomitant retinal vein occlusion (RVO) and to compare its diagnostic accuracy with that of ophthalmology residents and specialists. Methods: Fundus photographs of eyes with RVO and those with both RVO and glaucoma were obtained from patients who visited the University of Yamanashi Hospital. All images were preprocessed through normalization and resized to 512 × 512 pixels to ensure uniformity before model training. The diagnostic accuracy of two algorithms—the Comprehensive Fundus Disease Diagnostic Artificial Intelligence Algorithm (CD-AI) and the Glaucoma Concomitant RVO Artificial Intelligence Algorithm (RVO-GLA AI)—was evaluated. CD-AI is a clinical decision support algorithm originally developed to detect eleven common fundus diseases, including glaucoma and RVO. RVO-GLA AI is a fine-tuned version of CD-AI that is specifically adapted to detect glaucoma with or without RVO. Fine-tuning was performed using 1234 images of glaucoma, 1233 images of nonglaucomatous conditions, including RVO, and 15 images of cases with both glaucoma and RVO. The number of comorbid cases was determined empirically by gradually adding glaucomatous eyes with concomitant RVO to the training set, and 15 images provided the best balance between sensitivity and specificity. Because the available number of such cases was limited, this small sample size may have influenced the stability of the performance estimates. For the final evaluation, both algorithms and all ophthalmologists assessed the same independent test dataset comprising 66 fundus images (16 eyes with glaucoma and RVO and 50 eyes with RVO alone). The diagnostic performance of both algorithms was compared with that of three first-year ophthalmology residents and three board-certified ophthalmologists. Results: CD-AI demonstrated high diagnostic accuracy (92.5%) in eyes with glaucoma alone. However, its sensitivity and specificity decreased to 0.375 and 1.0, respectively, in patients with concomitant RVO. In contrast, the RVO-GLA AI achieved an area under the curve (AUC) of 0.875, with a sensitivity of 0.87 and a specificity of 0.71. Across all the ophthalmologists, the average sensitivity was 0.63, and the specificity was 0.87. Specialists achieved a sensitivity of 0.80 and a specificity of 0.89, while residents had a sensitivity of 0.46 and a specificity of 0.85. Conclusions: An AI-based clinical decision support system specifically designed for glaucoma detection significantly improved diagnostic performance in eyes with combined RVO and glaucoma, achieving an accuracy comparable to that of ophthalmologists, even with a limited number of training cases. Full article

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

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10 pages, 455 KB

Open AccessArticle

Retinal Nerve Fiber Layer Changes Following Cataract Surgery in Patients with and Without Preperimetric Glaucoma

by Feliciana Menna, Laura De Luca, Mattia Calabro, Alessandro Meduri, Stefano Lupo and Enzo Maria Vingolo

J. Clin. Med. 2025, 14(20), 7255; https://doi.org/10.3390/jcm14207255 - 14 Oct 2025

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Abstract

Background: Preperimetric glaucoma (PPG) is characterized by structural optic nerve damage without detectable functional impairment. Optical coherence tomography (OCT) is increasingly utilized to monitor glaucoma, though its reliability can be compromised by lens opacities. This study investigates retinal nerve fiber layer (RNFL) thickness changes after cataract surgery in patients with and without PPG, aiming to assess potential diagnostic inaccuracies due to cataract-induced imaging artifacts. Methods: Thirty eyes from 30 patients undergoing cataract surgery were analyzed, divided into two groups: Group 1 (n = 15) without glaucoma and Group 2 (n = 15) with PPG diagnosed using the Global Glaucoma Staging System. RNFL thickness was measured using Spectral-Domain OCT before and one month after phacoemulsification. Statistical analysis was performed using SPSS v23.0. Results: Postoperative RNFL thickness increased significantly in both groups, with a greater mean change in the PPG group (mean increase: 13 µm vs. 7 µm in controls; p < 0.00001). The greatest changes were observed in the inferior quadrants (p < 0.001). Image quality improved by approximately 34% post-surgery (p < 0.001). Despite higher postoperative RNFL values, none of the PPG eyes were reclassified as normal. Conclusions: In eyes with mild nuclear cataract, lens-related signal attenuation reduces absolute RNFL values but, in this cohort, had negligible impact on structural diagnostic classification. OCT-based structural findings in early glaucoma should therefore be interpreted with caution in the presence of cataract—recognizing that measurement bias may alter thickness values without changing PPG classification. Cataract surgery improves OCT reliability and can refine subsequent glaucoma assessment. Full article

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

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12 pages, 1571 KB

Open AccessArticle

Retinal Vascular Density and Vessel Diameter in Sturge–Weber Syndrome Assessed by OCT-Angiography

by Rosa Longo, Elena Gusson, Erika Lorenzetto, Luca Polinelli, Mariaelena Malvasi, Giacomo Panozzo and Giorgio Marchini

J. Clin. Med. 2025, 14(19), 7061; https://doi.org/10.3390/jcm14197061 - 6 Oct 2025

Viewed by 1065

Abstract

Background: Sturge–Weber syndrome (SWS) typically presents with a port-wine stain on the face, accompanied by leptomeningeal capillary malformations and ocular vascular anomalies. The aim of our study was to evaluate retinal vascular density and vessel diameter to better characterize the presence of vascular alterations. Methods: 15 patients diagnosed with Sturge–Weber syndrome and 15 healthy controls underwent comprehensive ophthalmologic evaluation, Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), to evaluate the microvascular architecture of the retina and choroid. Results: Analysis of the processed images revealed a significant increase (p < 0.05 *) in the density of the deep capillary plexus in patients with SWS compared to healthy controls. Vascular diameter was found to be increased overall in several retinal vascular plexuses in SWS patients compared to controls, reaching statistical significance (p < 0.05 *) in the deep vascular complex. Conclusions: The findings from our analysis highlight the potential role of OCTA in predicting the progression or worsening of ocular diseases over time. The introduction of new assessment parameters offers additional perspectives in evaluating ocular health. Since this examination allows for the detection of changes in the morphology and density of blood vessels as revealed by OCTA, these changes can be correlated with disease progression and the effectiveness of therapies. Full article

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

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Review

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25 pages, 408 KB

Open AccessReview

Trabecular Meshwork-Based MIGS: Efficacy, Technique Variability, and Wound Healing—A Comprehensive Review

by Fahad R. Butt, Thanansayan Dhivagaran, Jacob Stasso, Kyran Sachdeva, Luckshann Arunasalam, Fatima Abid, Brendan K. Tao, Michael Balas and David J. Mathew

J. Clin. Med. 2026, 15(4), 1490; https://doi.org/10.3390/jcm15041490 - 13 Feb 2026

Viewed by 627

Abstract

Background: Glaucoma, a leading cause of blindness worldwide, can be managed surgically when medical treatments are insufficient. Trabecular meshwork (TM)-based micro-invasive glaucoma surgery (MIGS) has emerged as a less invasive surgical approach to lowering intraocular pressure (IOP) and managing glaucoma. Methods: This narrative review synthesizes the scientific literature and trials on TM-based MIGS techniques, including trabecular micro-bypass stents, goniotomy and trabeculotomy procedures, electrocautery and laser-based approaches, and ab interno canaloplasty. Among these techniques, efficacy, pivotal clinical trials, medication reduction, safety profiles, complications, and determinants of surgical success were examined. Results: While all TM-based MIGS devices assessed achieved meaningful IOP reduction compared with trabeculectomies, there was no consensus on which TM-based MIGS technique yielded the best outcomes. TM-based MIGS had a good safety profile compared with traditional glaucoma surgeries. Common postoperative complications included transient hyphema, corneal edema, and anterior chamber inflammation. Ultimately, the success of TM-based MIGS procedures depended on many factors, including surgical technique, device type, and patient-specific factors. Conclusions: TM-based MIGS are an effective and safe surgical management option for eligible glaucoma patients requiring moderate IOP reduction. Future research should focus on the long-term outcomes of MIGS procedures, compare MIS devices, and explore the mechanistic and histopathological changes induced by MIGS. Full article

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

13 pages, 625 KB

Open AccessReview

Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Clinical Gradation and Current Therapeutic Strategies

by Martyna Tomczyk-Socha, Artur Małyszczak and Anna Turno-Kręcicka

J. Clin. Med. 2026, 15(2), 591; https://doi.org/10.3390/jcm15020591 - 12 Jan 2026

Viewed by 823

Abstract

The classic triad of clinical findings in pigment dispersion syndrome was described decades ago. It consists of radial, spoke-like iris transillumination defects, pigment deposits on the corneal endothelium known as the Krukenberg spindle, and a densely and homogenously pigmented trabecular meshwork. PDS occurs approximately three times more frequently in young myopic men than in women and is most often identified between 30 and 50 years of age. The diagnostic evaluation does not differ from the standard examination performed in patients with suspected glaucomatous optic neuropathy. However, it must additionally incorporate examinations specific to PDS. The possible therapeutic approaches varying by disease stage will be discussed, including pharmacologic treatment, laser procedures (iridotomy and trabeculoplasty), and surgical approaches such as canaloplasty, trabeculectomy, and other glaucoma surgeries. In order to better identify patients requiring an optimal therapeutic strategy, we propose a division into five stages of PDS: (1) preclinical PDS, (2) visible PDS, (3) PDS converting to pigmentary glaucoma, (4) pigmentary glaucoma, and (5) inactive PDS. Therapeutic strategies of each stage are described below. Full article

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

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33 pages, 683 KB

Open AccessFeature PaperReview

Next-Gen Neuroprotection in Glaucoma: Synergistic Molecules for Targeted Therapy

by Alessio Martucci, Massimo Cesareo, Maria Dolores Pinazo-Durán, Francesco Aiello, Giulio Pocobelli, Raffaele Mancino and Carlo Nucci

J. Clin. Med. 2025, 14(17), 6145; https://doi.org/10.3390/jcm14176145 - 30 Aug 2025

Cited by 4 | Viewed by 4901

Abstract

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

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

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