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Advances in Corneal Management
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Advances in Corneal Management

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (20 April 2026) | Viewed by 11903

Special Issue Editors

Dr. Sanja Masnec

E-Mail Website
Guest Editor
Department of Ophthalmology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Interests: cornea; crosslinking; corneal transplantations; anterior segment diseases; cataract surgeries; dry eye disease; ophthalmic plastic and reconstructive surgeries
Prof. Dr. Rafael I. Barraquer

E-Mail Website
Guest Editor
Institut Universitari Barraquer, Autonomous University of Barcelona, Barcelona, Spain
Interests: keratoconus; corneal topography; cataract surgery; refractive surgery; laser corneal surgery; corneal diseases; astigmatism; refractive eye surgery; intraocular lens; presbyopia

Special Issue Information

Dear Colleagues,

Corneal disease and transplantation have represented prominent topics of interest since ancient times, with the first methods for corneal transplantation dating back to the ancient Greek physician Galen. The first successful human corneal transplantation was performed in 1905 by Eduard Zinn, and, since then, progress in this field has been remarkable. However, in some cases, the management and treatment of numerous corneal conditions/illnesses, such as keratoconus, Fuchs’ dystrophy, corneal ulcers, infections, and various traumas, remains a challenge. As these disorders affect millions of people globally and frequently result in severe visual impairment, novel therapeutic strategies are required.

In addition to the above, this Special Issue will also focus on novelties in the field of refractive surgery, which has revolutionized vision correction. While advancements in corneal remodeling techniques continue to evolve, together with new possibilities, they also bring with them many challenges.

Our aim in launching this Special Issue is to present novel and original research, reviews, and clinical studies in the field of corneal diseases/conditions, corneal transplantation, and refractive surgery in order to provide an overview of current knowledge, therapeutic options, and future research directions in this field. We are eager to publish not only clinical work but also pre-clinical and laboratory research that can help us understand the mechanisms responsible for corneal pathology and its treatment. Studies exploring novel diagnostic tools and therapeutic approaches are particularly welcome.

We look forward to advancing and developing research on corneal illness and transplantation, in addition to refractive surgery, by bringing together innovative studies and a range of viewpoints.

Dr. Sanja Masnec
Prof. Dr. Rafael I. Barraquer
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cornea
  • corneal disease
  • corneal transplantation
  • keratoconus
  • keratoplasty
  • penetrating keratoplasty
  • descemet stripping automated endothelial keratoplasty
  • deep anterior lamellar keratoplasty
  • descemet membrane endothelial keratoplasty
  • cross-linking
  • corneal infections
  • refractive surgery
  • photorefractive keratectomy
  • laser-assisted in situ keratomileusis
  • kerato–lenticule extraction
  • corneal imaging

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Published Papers (8 papers)

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Research

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12 pages, 1646 KB  
Article
Deferoxamine Modulates Corneal Endothelial Cell Biological Properties Associated with Increased VEGF Expression
by Barbara Sophie Brunner, Paul Emesz, Nikolaus Luft, Siegfried Georg Priglinger, Andreas Ohlmann and Stefan Kassumeh
Medicina 2026, 62(5), 808; https://doi.org/10.3390/medicina62050808 - 23 Apr 2026
Viewed by 326
Abstract
Background and Objectives: The objective of this study is to evaluate whether deferoxamine modulates cell biological properties, such as proliferation and wound closure of porcine corneal endothelial cells (CECs) in vitro, and whether the treatment of CECs with deferoxamine results in an enhanced [...] Read more.
Background and Objectives: The objective of this study is to evaluate whether deferoxamine modulates cell biological properties, such as proliferation and wound closure of porcine corneal endothelial cells (CECs) in vitro, and whether the treatment of CECs with deferoxamine results in an enhanced expression of vascular endothelial growth factor (VEGF). Materials and Methods: Corneal endothelial cells were extracted from porcine globes within 24 h postmortem. Immunohistochemistry for the endothelial Na+/K+-ATPase was performed to confirm the cells’ endothelial origin. To assess CEC viability and proliferation, a water-soluble tetrazolium salt (WST-1) and 5-bromo-2′-deoxyuridine (BrdU) assay were performed. Corneal endothelial wound closure was evaluated using a wound closure assay. VEGF mRNA expression was evaluated using real-time polymerase chain reaction (rt-PCR). Results: The extracted corneal endothelial cells showed a typical hexagonal morphology with Na+/K+-ATPase staining of the cell membrane. The treatment with 200 µM deferoxamine significantly increased CEC viability to 121 ± 24% compared to the control group (p = 0.0024). Corneal endothelial cell proliferation did not show any significant changes under the treatment with deferoxamine (p > 0.05). Both 100 µM and 200 µM deferoxamine led to a significantly smaller remaining wound area of 82.4 ± 6.7% and 78.7 ± 6.2% (p < 0.0001) in comparison to the control group after 24 h of treatment in the wound closure assay. Treatment with 200 µM deferoxamine significantly induced VEGF mRNA expression to 1.67- ± 0.57-fold from 1.00- ± 0.03-fold in the control group (p = 0.0006). Conclusions: Deferoxamine effectively enhances corneal endothelial cell viability and wound healing associated with an overexpression of VEGF. Thus, deferoxamine is a potent modulator of cell biological properties of corneal endothelial cells and maintains their integrity in vitro. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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9 pages, 266 KB  
Article
Serum Markers of Oxidative Stress and Antioxidant Status in Keratoconus: Ischemia-Modified Albumin, Malondialdehyde, and Total Thiol Levels
by Serek Tekin, Erbil Seven, Canan Demir, Halit Demir, Muhammed Batur, Muhammet Derda Özer and Tekin Yaşar
Medicina 2026, 62(4), 682; https://doi.org/10.3390/medicina62040682 - 2 Apr 2026
Viewed by 496
Abstract
Background and Objectives: Keratoconus (KC) is a progressive corneal ectatic disorder characterized by stromal thinning, irregular astigmatism, and visual impairment. Increasing evidence suggests that oxidative stress plays a significant role in the pathogenesis of KC. Biomarkers such as ischemia-modified albumin (IMA), malondialdehyde (MDA) [...] Read more.
Background and Objectives: Keratoconus (KC) is a progressive corneal ectatic disorder characterized by stromal thinning, irregular astigmatism, and visual impairment. Increasing evidence suggests that oxidative stress plays a significant role in the pathogenesis of KC. Biomarkers such as ischemia-modified albumin (IMA), malondialdehyde (MDA) and total thiol (TT) have been widely used to assess oxidative status. This study aims to evaluate the role of oxidative stress in KC disease by comparing serum levels of IMA, MDA, and TT between KC patients and healthy controls. Material and Methods: Forty patients diagnosed with KC and 43 healthy individuals of similar age and gender were included in the study. Patients with KC were classified in 4 stages according to the modified Krumeich KC classification system. IMA, MDA, and TT levels were compared in serum samples from patient and control groups. Results: Serum IMA levels were 2.52 ± 0.07 in the KC group and 1.2 ± 0.03 in the control group. The difference was statistically significant (p < 0.001). While serum MDA levels were 1.68 ± 0.05 in the KC group, they were 0.74 ± 0.04 in the control group. The difference was statistically significant (p < 0.001). Serum TT levels were 0.82 ± 0.41 in the KC group and 2.23 ± 0.04 in the control group. The difference was statistically significant (p < 0.001). Conclusions: Elevated serum IMA and MDA levels, together with decreased TT levels, in patients with KC are likely associated with increased oxidative stress. These parameters may serve as auxiliary biomarkers for evaluating disease pathophysiology and may represent potential targets for future diagnostic and therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
15 pages, 4800 KB  
Article
Impact of Dry Eye Disease and Lipid-Containing Artificial Tears on Keratometric Reproducibility and Intraocular Lens Calculation in Cataract Patients
by Valentina Lacmanović Lončar, Danijel Mikulić, Vedrana Aljinović-Vučić, Zoran Vatavuk and Ivanka Petric Vicković
Medicina 2026, 62(1), 179; https://doi.org/10.3390/medicina62010179 - 15 Jan 2026
Viewed by 952
Abstract
Background and Objectives: Tear film instability and corneal surface irregularity are important sources of variability in keratometric and corneal topographic measurements, particularly affecting astigmatic magnitude and axis. Accurate preoperative biometry is crucial for optimal refractive outcomes in cataract surgery. Dry eye disease [...] Read more.
Background and Objectives: Tear film instability and corneal surface irregularity are important sources of variability in keratometric and corneal topographic measurements, particularly affecting astigmatic magnitude and axis. Accurate preoperative biometry is crucial for optimal refractive outcomes in cataract surgery. Dry eye disease (DED) may compromise the reproducibility of keratometric parameters, leading to errors in intraocular lens (IOL) power calculation. This study aimed to evaluate the impact of DED on the reproducibility of keratometric measurements and to assess the effect of a four-week treatment with lipid-containing artificial tears on these parameters in cataract patients. Materials and Methods: This cross-sectional study included 116 patients scheduled for cataract surgery, of whom 65 (56.0%) had DED and 51 (44.0%) served as controls. All patients underwent two preoperative keratometric measurements 10–20 min apart (IOL1 and IOL2). The control group proceeded to surgery the next day, while surgery in the DED group was postponed. Patients with DED received preoperative therapy with lipid-containing artificial tears. Follow-up assessments occurred one month after therapy (keratometric measurement named IOL3) and eight weeks postoperatively. Clinical evaluation included slit-lamp examination, dry eye testing according to Dry eye Workshop II (DEWS II) criteria: Ocular surface Disease Index (OSDI), Tear Break-Up Time (TBUT), Schirmer I, Oxford staining, and meibomian gland assessment), ocular biometry, and postoperative spherical equivalent measurement using an auto ref-keratometer. Nonparametric statistical analyses were applied to evaluate associations between parameters. Results: In the DED group, corneal astigmatism showed a significant difference between IOL1 and IOL2 (Wilcoxon signed-rank test {Z = 2.43; p = 0.015}). Significant changes in predicted IOL power were observed between pretreatment and posttreatment values (t = 2.57; p = 0.013) and between IOL2 and IOL3 (t = 2.23; p = 0.029), indicating improved keratometric stability following tear film therapy. No additional significant correlations were identified. Conclusions: DED adversely affects the reproducibility of keratometric measurements and may compromise IOL power selection. Preoperative identification and treatment of DED, followed by repeated biometry after tear film stabilization, are strongly recommended to enhance refractive accuracy and optimize surgical outcomes in cataract patients. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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13 pages, 977 KB  
Article
Can Insulin Drops Accelerate Corneal Healing After Corneal Cross-Linking? A Preliminary Case Series
by Freja Bagatin, Ante Vukojević, Karla Ranđelović, Ivana Radman, Renata Iveković, Valentina Lacmanović Lončar, Ivanka Petric Vicković and Zoran Vatavuk
Medicina 2025, 61(12), 2101; https://doi.org/10.3390/medicina61122101 - 26 Nov 2025
Viewed by 1035
Abstract
Background and Objectives: Corneal cross-linking (CXL) is the standard treatment for progressive keratoconus, but delayed epithelial healing remains a concern, increasing infection risk and patient discomfort. Studies suggest that insulin may promote corneal epithelial cell migration and proliferation, potentially accelerating wound healing. Its [...] Read more.
Background and Objectives: Corneal cross-linking (CXL) is the standard treatment for progressive keratoconus, but delayed epithelial healing remains a concern, increasing infection risk and patient discomfort. Studies suggest that insulin may promote corneal epithelial cell migration and proliferation, potentially accelerating wound healing. Its benefit has been observed in neurotrophic keratitis and diabetic epithelial defects, and it may offer similar effects post-CXL. Our objective is to evaluate the effect of topical insulin on epithelial healing after CXL in a small case series. Materials and Methods: Eight patients undergoing CXL for keratoconus were divided into two groups (n = 4 each). The insulin group received topical insulin eye drops (1 IU/mL in Systane®) five times daily, in addition to standard postoperative care. The control group received Systane® alone with the same regimen. Daily follow-up included slit-lamp exam, anterior segment OCT, and photodocumentation until epithelial defect closure. Results: Baseline parameters (central corneal thickness, keratoconus stage, Schirmer test, tear break up test) were comparable. While not statistically significant, the insulin group showed numerically smaller epithelial defects on day 2, suggesting a possible trend toward faster healing. By day 3, re-epithelialization was complete in all patients. Pain decreased over time in both groups without significant differences. No adverse effects were noted. Conclusions: Topical insulin may modestly accelerate epithelial healing after CXL, as suggested by smaller defects on day 2 in the insulin group. Although results were not statistically significant, the trend warrants further investigation in larger studies. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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9 pages, 555 KB  
Article
Efficacy of Insulin Eye Drops in the Treatment of Corneal Ulcers in Patients with Facial Nerve Palsy and Lagophthalmos: A Retrospective Case–Control Study
by Marija Jelić Vuković, Suzana Matić, Dubravka Biuk, Miro Kalauz, Andrijana Kopić, Vedran Nemet, Ivana Strunje, Ivanka Maduna, Stipe Vidović and Ena Kolak
Medicina 2025, 61(11), 1991; https://doi.org/10.3390/medicina61111991 - 6 Nov 2025
Viewed by 1199
Abstract
Background and Objectives: Corneal ulcers in patients with lagophthalmos due to facial nerve palsy pose a significant therapeutic challenge. Topical insulin has emerged as a promising adjuvant therapy for enhancing corneal re-epithelialization. The aim of this study is to evaluate the efficacy of [...] Read more.
Background and Objectives: Corneal ulcers in patients with lagophthalmos due to facial nerve palsy pose a significant therapeutic challenge. Topical insulin has emerged as a promising adjuvant therapy for enhancing corneal re-epithelialization. The aim of this study is to evaluate the efficacy of insulin drops compared with lipid-based artificial tears, and to compare the corneal healing rate in achieving complete epithelialization within 30 days in diabetic patients. Materials and Methods: This retrospective case–control study included 32 patients with facial nerve palsy and lagophthalmos who developed an exposed corneal ulcer, of whom 20 received topical insulin and 12 received lipid-based artificial tears. The primary outcome was complete epithelialization at day 30. Additional variables included age, sex, and baseline defect characteristics. Results: By day 30, complete epithelialization was achieved in 18 of 20 patients (90%) in the insulin group compared with 5 of 12 (41.7%) in the control group. Binary logistic regression analysis confirmed significantly higher odds of healing with insulin treatment (OR = 10.8; 95% CI 1.8–63.9). No systemic adverse events or signs of hypoglycemia were observed. Conclusions: Topical insulin significantly accelerates corneal epithelialization in patients with facial nerve palsy and exposed ulcers, offering safe and effective adjuvant therapy for a high-risk population. Despite promising results, the study’s limitations—including small sample size, single-center design, and retrospective nature—highlight the need for larger, multicenter prospective studies to confirm efficacy, optimize dosing, and further evaluate long-term safety. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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10 pages, 265 KB  
Article
Comparative Analysis of Corneal Densitometry Changes Following Standard Versus Accelerated Corneal Cross-Linking Protocol
by Lorena Karla Šklebar, Sonja Jandroković, Miro Kalauz, Ivan Škegro, Dina Lešin Gaćina, Iva Bešlić, Ivana Gabrić, Niko Tomljanović, Božana Mrvelj and Sania Vidas Pauk
Medicina 2025, 61(11), 1928; https://doi.org/10.3390/medicina61111928 - 28 Oct 2025
Cited by 1 | Viewed by 792
Abstract
Background and Objectives: The aim of this study is to evaluate and compare changes in corneal densitometry after standard (30 min exposure time of 3 mW/cm2 UVA) and accelerated (10 min exposure time of 9 mW/cm2 UVA) protocols of corneal [...] Read more.
Background and Objectives: The aim of this study is to evaluate and compare changes in corneal densitometry after standard (30 min exposure time of 3 mW/cm2 UVA) and accelerated (10 min exposure time of 9 mW/cm2 UVA) protocols of corneal cross-linking (CXL) in patients with progressive keratoconus. Materials and Methods: This study included a total of 38 eyes of 38 patients divided into two equal-sized subgroups. CXL was performed in one group according to the standard epithelium-off protocol (30 min, 3 mW/cm2 UVA) and in the other group according to an accelerated epithelium-off protocol (10 min, 9 mW/cm2 UVA). Scheimpflug imaging was used to evaluate corneal densitometry in the anterior, central, and posterior corneal layers in three concentric zones (0–2 mm, 2–6 mm, and 6–10 mm) at baseline and 1, 3, and 9 months after surgery. Results: This study included 38 patients divided into two subgroups of 19. One group of patients underwent standard and the other accelerated CXL protocol. Participants in the accelerated group were significantly older (p < 0.001). 9 months after CXL treatment, the accelerated group showed higher central and posterior corneal densitometry values, but, after adjusting for age and baseline values, ANCOVA analysis revealed no significant intergroup differences. Both protocols led to overall reductions in corneal densitometry over time. Conclusions: Both the standard and accelerated CXL protocols induce transient corneal haze, which can be objectified by increased corneal densitometry values in first three months post-CXL. The dynamics of the onset and recovery of postoperative corneal haze are comparable and similar in both protocols. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
12 pages, 896 KB  
Article
Comparative Analysis of Corneal Morphological and Optical Parameters in Predicting DSAEK Surgery Outcome
by Antonela Geber, Sanja Masnec, Miro Kalauz, Iva Bešlić, Ivan Škegro, Dina Lešin Gaćina, Sonja Jandroković, Ana Meter and Tomislav Kuzman
Medicina 2025, 61(6), 1022; https://doi.org/10.3390/medicina61061022 - 31 May 2025
Cited by 1 | Viewed by 1165
Abstract
Background and Objectives: Descemet stripping automated endothelial keratoplasty (DSAEK) is a widely used surgical technique for treating corneal endothelial dysfunctions such as Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). This study aimed to investigate the association between postoperative visual [...] Read more.
Background and Objectives: Descemet stripping automated endothelial keratoplasty (DSAEK) is a widely used surgical technique for treating corneal endothelial dysfunctions such as Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). This study aimed to investigate the association between postoperative visual acuity and various corneal morphological and optical parameters, including corneal densitometry (CD) and higher-order aberrations (HOAs), measured using the Pentacam (OCULUS Optikgeräte GmbH, Wetzlar, Germany), as well as graft thickness, which was assessed by anterior segment optic coherence tomography (AS-OCT), (Optovue Inc., Fremont, CA, USA), and corneal thickness, assessed by both AS-OCT and Pentacam. Materials and Methods: This prospective, observational cohort study included 17 eyes from 13 patients who underwent DSAEK. Data on preoperative visual acuity were collected, while postoperative parameters were assessed during follow-up visits. Corneal measurements included the total corneal and corneal graft thickness, corneal densitometry in 20 defined subregions, and corneal higher-order aberrations. Associations between these parameters and postoperative visual acuity were evaluated using nonparametric statistical tests. Results: The postoperative visual acuity improved significantly (p < 0.001). Strong correlations were found between poorer visual acuity and higher CD values. The strongest correlations with visual acuity were found for CD 2–6 mm total (Rho = 0.795; p < 0.001), CD central 2–6 mm (Rho = 0.791; p < 0.001), and CD central 0–2 mm (Rho = 0.730; p < 0.001). Significant associations were also observed with anterior and posterior HOAs (Rho = 0.624, p = 0.01; and Rho = 0.556, p = 0.02, respectively). No correlation was found between visual outcomes and graft thickness measured by AS-OCT (Rho = 0.051; p = 0.85), nor with total corneal thickness measured by AS-OCT (Rho = −0.227; p = 0.38) or Pentacam (Rho = −0.369; p = 0.14). Conclusions: This study demonstrates that CD and HOAs are more strongly associated with postoperative visual acuity after DSAEK than traditionally monitored parameters such as graft or corneal thickness. The results highlight the value of detailed corneal imaging and support the use of advanced optical diagnostics in postoperative evaluation. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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Review

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9 pages, 731 KB  
Review
Rho-Kinase Inhibitors in the Management of Fuchs Endothelial Corneal Dystrophy: A Review
by Anđela Jukić, Ana Pupić Bakrač, Biljana Đapic Ivančić, Andrijana Kopić, Ana Meter, Rajka Kasalica Žužul, Josip Pavan and Tomislav Jukić
Medicina 2025, 61(5), 772; https://doi.org/10.3390/medicina61050772 - 22 Apr 2025
Cited by 4 | Viewed by 4748
Abstract
Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, [...] Read more.
Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, but it has limitations such as donor shortages, infection risk, and graft rejection. Rho-kinase (ROCK) inhibitors have emerged as a promising pharmacological alternative. These agents promote CEC proliferation, migration, and adhesion while inhibiting apoptosis and enhancing corneal endothelial wound healing. Several studies have demonstrated the efficacy of ROCK inhibitors in improving corneal clarity and endothelial function, particularly when used as an adjunct to Descemet Stripping Only (DSO) surgery. Additionally, they show potential in preventing corneal edema in FECD patients undergoing cataract surgery. The methodology involved a literature search through the PubMed and Medline databases using relevant keywords. Only peer-reviewed articles in English were included, with additional references from selected articles reviewed to ensure comprehensive coverage. ROCK inhibitors offer a novel pharmacological approach to managing FECD. They have shown potential in promoting endothelial cell regeneration and improving corneal functIion. Despite promising results, further research is required to determine ROCK inhibitors’ long-term safety, optimal dosing, and efficacy in surgical and non-surgical FECD patients. Their potential to delay or prevent corneal transplantation represents a significant advancement in FECD management. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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