Open research questions in Corneal surgery and disorders

What the literature leaves open

• Slit-lamp examination revealed bilateral grayish-white stromal deposits with poorly defined borders and diffuse stromal haze of variable severity, while AS-OCT demonstrated subepithelial hyperreflective deposits associated with diffuse stromal hyperreflectivity and reduced central corneal thickness.

  Clinical and tomographic features of a presumed macular corneal dystrophy in a Moroccan sibling cohort · 2026 · DOI

• This analysis is cross-sectional; it defines risk at a single time point rather than tracking progression. The per-diopter odds increment (OR 1.83) describes association, not trajectory. Longitudinal cohort studies are needed to establish rates of change in this population and to determine whether age modifies the astigmatism-KC relationship. Such designs would also clarify which normal-appearing corneas progress to ectasia over time. Measurement repeatability may be reduced in advanced KC due to corneal irregularity, introducing variability that could affect classification. We did not control for ocular surface disease, which may influence keratometry and introduce measurement bias. Higher-order aberrations, integrated with tomographic data, may improve sensitivity for subclinical disease in future models.

  Deciphering the Astigmatic Code in Libyan Keratoconus: From Epidemiological Trends to Clinical Precision · 2026 · DOI

• The application of artificial intelligence (AI) in the diagnosis and management of RCES is a promising yet underexplored area of research. While AI has demonstrated significant utility in the detection and monitoring of other corneal diseases such as keratoconus and infectious keratitis, its use in RCES-related imaging remains in its infancy. Future research should prioritize the development and validation of artificial intelligence (AI)-driven algorithms capable of synthesizing complex data from multimodal imaging platforms. By leveraging deep learning to analyze high-resolution imaging, these systems can identify discrete microstructural corneal changes that serve as biomarkers of disease recurrence, thus aiding in lowering disease morbidity.

  Seeing Through the Layers: Imaging Innovations in Recurrent Corneal Erosion Syndrome · 2026 · DOI

• As a single case study, this report features several key limitations. The nature of the alternative proposed mechanisms for CECL remains highly speculative and theoretical. The relationship between irradiation and polyimide biocompatibility, as well as the presence of foreign body reactions, represents areas that require further in vivo research to establish whether any relationship is present. In addition, the lack of any chronic inflammatory reaction to be observed in our patient makes it less likely for this to be a significant feature of our case. Although the geometry of the CyPass® stent in the anterior chamber angle minimizes the likelihood that device-cornea touch is a key contributor to CECL, no dynamic imaging was performed to definitively exclude this potential. Lastly, while ripasudil may have a corneal endothelial protective effect, larger-scale observational or randomized controlled trials are required to determine whether it has a role in managing MIGS-associated CECL.

  Delayed Corneal Endothelial Cell Loss Following CyPass Stent Insertion: A Case Report · 2026 · DOI

• Ghadeer Mohammed 1*, Muhammad Abbas Tayyab 2, Jaffer Hussain 2, Renad AlDhib 3, Mifrah Rahat Khan Sherwani 4, Johar Abbas 5, Zahra Arsalan 5 and Carolina Mercado 6* 1University of Kufa College of Medicine, Najaf, Iraq, 2King Edward Medical University, Lahore, Pakistan, 3MAHSA University, Selangor, Malaysia, 4Duke University Hospital, Durham, NC, United States, 5Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, 6Bascom Palmer Eye Institute, Naples, FL, United States Introduction: Corneal endothelial dysfunction, most commonly caused by Fuchs endothelial corneal dystrophy (FECD) or pseudophakic bullous keratopathy (PBK), leads to stromal edema and corneal decompensation when endothelial cell density (ECD) falls below 500–700cells/mm². Standard treatment via corneal transplantation, including Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK), is limited by the need to standardize corneal endothelial cell culture, donor shortages, immune rejection, and technical complications.This review aims to summarize recent advances in injectable corneal endothelial cell (CEC) therapy, critically appraise translational challenges, and discuss future directions for establishing this regenerative approach as a global treatment. Design: Narrative review of pre-clinical and clinical studies examining CEC injection therapy. Methods: Relevant literature was analyzed to evaluate innovations in Human corneal endothelial cells (HCEC) preparation, culture techniques, delivery methods, and strategies to enhance cell adhesion and survival. Studies reporting preclinical models and human clinical trials were included to assess safety, efficacy, and translational feasibility. Results: Corneal endothelial cells (CEC) injections have achieved significant advancement since their development. Simple cultured CEC injections showed poor efficacy due to limited cell adhesion and survival, but the introduction of ROCK inhibitors along with cultured CECs demonstrated improvement in corneal transparency up to 5 years. Advancements in cell delivery techniques like hydrogel, carrier-assisted injections, magnetically guided injections, as well as alternative cell sources have shown promising results in pre-clinical studies, but human studies are still ongoing. Despite advancements, persisting challenges include phenotypic stability, and longterm safety and efficacy.

  Injectable corneal endothelial cell therapy: recent progress, translational barriers, and future directions · 2026 · DOI

• This work addresses a known limitation of traditional Goldmann applanation tonometry (GAT), which assumes a structurally uni- form cornea and does not account for individual variations in FIGURE 7 Boxplot comparing Young’s modulus (E) between two age groups: 20–39 years and ≥40 years.

  Clinical evaluation of corneal elasticity and true IOP using a dual-applanation tonometer · 2026 · DOI

• Overall, the application of AI technology in the field of refractive surgery has made significant progress, with far-reaching impacts on improving surgical accuracy, formulating personalized surgical plans, and predicting postoperative complications. With the rapid development of big data and AI algorithms, the application of AI in refractive surgery will continue to deepen, advancing toward greater precision and intelligence. In the future, the application of AI will be in the following aspects: (1) AI-Driven primarily reflected Frontiers in Cell and Developmental Biology 08 frontiersin.org Ji et al. 10.3389/fcell.2026.1824307 surgical planning approaches will Preoperative Screening and Candidate Selection. In the future, with the accumulation of more high-quality clinical data, AI screening models will be continuously optimized. By integrating diverse examination data, such as corneal topography and corneal thickness, AI will form a more intelligent screening system. AI can not only improve screening accuracy but also significantly enhance diagnostic efficiency, enabling clinicians to identify highrisk patients more quickly and provide them with personalized treatment recommendations. As AI continues to advance in the field of medical image recognition, fully automated preoperative screening is expected to become a reality. This will allow clinicians to obtain comprehensive patient evaluation reports more efficiently, thereby optimizing clinical decision-making and improving the convenience and accuracy of screening. (2) AI- Assisted Surgical Planning and Individualized Treatment. In the future, AI will not only assist clinicians in surgical planning but also enhance the accuracy of surgical recommendations through continuous training and optimization. In complex cases, AI may even provide multiple surgical options. By learning the relationship between extensive preoperative examination data and postoperative refractive outcomes, AI models can accurately predict optimal surgical parameters. Furthermore, AI is expected to refine the calculation methods for surgical parameters and integrate realtime image analysis technology, enabling dynamic adjustments to surgical strategies during the procedure. This will further improve the precision and personalization of refractive surgery. Such intelligent enhance postoperative visual quality and reduce incidence of complications. (3) Application of AI in Predicting Postoperative Complications. The application of AI technology in postoperative management of refractive surgery is progressively deepening, offering new methods to improve postoperative safety and reduce complication rates.

  Artificial intelligence in refractive surgery: progress, challenges, and future directions · 2026 · DOI

• Yuke Ji 1†, Lu Xie 2†, Fangyan Liu 2, Yanwu Xu 3, Weihua Yang 2* and Shaochong Zhang 1,2* 1Shenzhen Eye Hospital, Jinan University, Shenzhen, Guangdong, China, 2Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, Guangdong, China, 3School of Future Technology, South China University of Technology, Guangzhou, China The rapid evolution of artificial intelligence (AI) has catalyzed significant advancements in ophthalmology. As refractive surgery necessitates increasing levels of precision and personalization, AI offers pivotal solutions for optimizing clinical outcomes. This review systematically summarizes recent progress in applying machine learning and deep learning models to corneal refractive surgery and implantable collamer lens (ICL) procedures. Specifically, we examine AI’s utility in preoperative candidate screening, personalized surgical planning, and the prediction of postoperative complications. Although AI demonstrates broad prospects for enhancing surgical decision-making, several challenges remain, including data standardization, algorithm interpretability, cross-device compatibility, and ethical considerations. Overall, AI-driven decision-support systems are accelerating the transition of refractive surgery from standardized protocols to data-driven, individualized management, with the potential to enable more intelligent, automated, and precise surgical correction in ophthalmology.

  Artificial intelligence in refractive surgery: progress, challenges, and future directions · 2026 · DOI

• Future research should focus on validating the proposed frame- work using larger multicenter datasets that include diverse populations and imaging platforms. Integration of additional diagnostic modali- ties, such as corneal tomography, biomechanical measurements, or anterior segment optical coherence tomography, may further enhance the robustness of early keratoconus detection. In addition, the neuro- symbolic reasoning architecture may be extended to other ophthalmic diagnostic tasks, including glaucoma risk assessment, corneal dystro- phy classification, and refractive surgery planning. From a broader perspective, combining symbolic clinical knowl- edge, deep learning representations, and explainable language models represents a promising direction for the development of transparent and trustworthy medical AI systems. Such hybrid approaches may help address one of the central challenges in clinical AI: balancing predictive performance with interpretability and clinical accountability.

  Explainable neuro-symbolic artificial intelligence for automated interpretation of corneal topography and early keratoconus detection · 2026 · DOI

• While previous studies identified predictors of successful surgical outcomes (younger age, lower SE, male gender) and factors influencing dominant eye selection, insights into personalized treatment strategies and their role in maximizing patient satisfaction remain areas for further investigation.

  Unveiling Common LASIK Complications: A Machine-Learning Based Analysis of FDA Reported Cases · 2026 · DOI

• Over half of the subjects could not be assessed with the standard Cochet-Bonnet filament and 11% could not be assessed with either filament, as their corneal sensitivity was outside of the range of the instrument.

  The Dawn Chorus: Children's Writing as a Transitional Art. · 1989 · DOI

• Although the reported results are encouraging, several barriers remain, including limited external validation, lack of standardized datasets, and concerns about model interpretability.

  Clinical application of artificial intelligence in corneal transplantation · 2026 · DOI

• Future studies incorporating a wider sampling area, including the inferior and inferotemporal quadrants, are warranted to comprehensively evaluate regional variations in corneal remodeling.

  Orthokeratology for stable mild-to-moderate keratoconus: a pilot study on safety and corneal remodeling via quantitative OCT analysis · 2026 · DOI

• The homogeneous and poorly defined hyperreflectivity of the iris pigment epithelium was attenuated or completely absent in the most clinically affected areas, allowing light transmission.

  Acute Unilateral Iris Transillumination Following Topical Moxifloxacin: A Case Report and Anterior Segment Optical Coherence Tomography Findings · 2026 · DOI

• The hemodynamic characteristics of individual ocular vessels in stromal herpetic keratitis (SHK) remain unknown.

  Hemodynamic changes in the ocular vessels in stromal herpetic keratitis according to ultrasound Doppler imaging · 2026 · DOI

• Despite high satisfaction rates, a subset of patients continues to experience unsatisfactory outcomes due to factors such as under or overcorrection, regression, or postoperative complications, indicating that success of refractive surgery is not universal.

  Unveiling Common LASIK Complications: A Machine-Learning Based Analysis of FDA Reported Cases · 2026 · DOI

• Future research should focus on investigating new local (ocular) and systemic (whole body) pathogenetic factors of diffuse lamellar keratitis following modern excimer laser methods for ametropia correction.

  On the issue of complications following excimer laser correction of ametropia · 2024 · DOI

• To date, many aspects of pathomorphological changes of the cornea in secondary dystrophies remain insufficiently studied due to the impossibility of conducting an intravital study of the cornea tissue.

  Pathomorphological Features of The Cornea in Secondary Posttraumatic Dystrophy (Clinical Case) · 2024 · DOI

Most-cited papers in Corneal surgery and disorders

• The Dawn Chorus: Children's Writing as a Transitional Art. · Use of English · 1989 · 123 citations
• IC3D Classification of Corneal Dystrophies—Edition 3 · Cornea · 2024 · 88 citations
• Descemet Stripping Endothelial Keratoplasty · Deutsches Ärzteblatt international · 2013 · 11 citations
• Corneal Biomechanics – an Emerging Ocular Property with a Significant Impact · MAEDICA – a Journal of Clinical Medicine · 2022 · 6 citations
• Evaluating the Influence of Eye Rubbing and Genetic Predisposition on Keratoconus in Bucaramanga (Colombia): A Case-control Study · Czech and Slovak Ophthalmology · 2025 · 4 citations
• Inter-eye asymmetry in manifest refraction, keratometry and pachymetry in eyes with keratoconus · Klinika Oczna · 2020 · 3 citations
• Determination of Corneal Power After Refractive Surgery with Excimer Laser: A Concise Review · Czech and Slovak Ophthalmology · 2023 · 3 citations
• Long-term results of Boston keratoprosthesis surgery in Polish patients · Postępy Higieny i Medycyny Doświadczalnej · 2022 · 2 citations
• Tomographic changes after corneal collagen cross-linking for progressive keratoconus - one-year follow-up study · Srpski arhiv za celokupno lekarstvo · 2022 · 2 citations
• Intraocular pressure and central corneal thickness in a healthy student population · Srpski arhiv za celokupno lekarstvo · 2024 · 2 citations

Most recent work

• Explainable neuro-symbolic artificial intelligence for automated interpretation of corneal topography and early keratoconus detection · Frontiers in Artificial Intelligence · 2026
• Dual-Zone Keratometry for Identifying Central Radius and Corneal Asphericity · Current Eye Research · 2026
• Device Selection Conundrum and Procedural Factors in the ROLLING STONE Registry · JACC: Cardiovascular Interventions · 2026
• Unveiling Common LASIK Complications: A Machine-Learning Based Analysis of FDA Reported Cases · CRO (Clinical & Refractive Optometry) Journal · 2026
• Neutrophil-to-Lymphocyte Ratio Is Associated with the Stability of Human Corneal Endothelial Cells · Journal of Clinical Medicine · 2026
• Sex differences in congenital hereditary endothelial dystrophy (CHED) and Slc4a11−/− mouse model of CHED · Biology of Sex Differences · 2026
• Gene expression and machine learning techniques uncover corneal biomarkers associated with oxidative stress in the myopia progression · Scientific Reports · 2026
• Epioxa: The First FDA-Approved epithelium-on-cross-linking therapy for keratoconus · Annals of Medicine & Surgery · 2026
• Orthokeratology for stable mild-to-moderate keratoconus: a pilot study on safety and corneal remodeling via quantitative OCT analysis · International Ophthalmology · 2026
• TGIF1-mediated corneal fibrosis inhibition: a gene-editing alternative to keratoplasty? · Annals of Medicine & Surgery · 2026

Related topics in Medicine