Abstract
Introduction
The prevalence of corneal diseases varies among different countries and populations. However, it can be leading cause of more than 6 million vision loss worldwide.1,2 Corneal diseases are the fifth cause of blindness, 3 and includes a wide range of eye inflammations and infections that may lead to corneal ulcers. 4
Factors such as aging, 5 infections, 6 genetic predispositions, 7 ocular traumas, 8 wearing contact lenses, 9 as well as systemic diseases like endocrine disorders, Graves’ disease, Addison's disease, hyperparathyroidism, viral and bacterial infections, autoimmune conditions, inflammatory disorders, and genetic abnormalities can lead to damage and dysfunction in cornea. 10 In fact, corneal diseases are among the most significant eye conditions that can lead to cloudiness, deviation, ulcers, and ultimately blindness. The most common corneal diseases are keratitis, dry eye, corneal ulcer, keratoconus, cataract, strabismus, and pterygium.11,12
Recently, healthcare organizations started using diverse information technologies and digital tools to provide high quality services. 12 In various medical fields, different information systems, such as clinical decision support systems (CDSS), have been used to facilitate data processing, data management, and disease diagnosis. CDSS are computer systems that influence physicians’ decision-making processes in various fields. These systems typically use various computer algorithms to process and analyze medical data, generate alternative decisions, and support diagnostic or therapeutic methods. 12
The use of CDSS in the field of ophthalmology has also increased. This approach has facilitated decision-making in complex diagnostic and therapeutic cases. Otherwise, the massive volume of generated data, especially in corneal diseases such as keratoconus, dry eye, corneal infection, cataracts, etc., makes the diagnostic process more challenging. 12 Given the importance of providing high quality eye care services and the high cost of potential errors, the necessity of using these systems to assist ophthalmologists is inevitable. Moreover, general practitioners (GPs) and primary eye care practitioners (like optometrists) can use these systems to improve early detection of anterior eye diseases, diagnose diseases quicker, and provide more precise treatment plans. Not only healthcare providers, but also patients can use this technology to monitor their own diseases. 13 Various studies showed that CDSSs have been used in many areas of ophthalmology14–23; however, only a few studies have focused on the development and evaluation of these systems for corneal diseases. Therefore, the aim of the present study was to conduct a systematic review of using CDSSs in corneal diseases. The results of this study can be used to identify gaps in the current knowledge and propose opportunities for future research in designing, implementation, and effective use of health information technology in ophthalmology, with a specific focus on corneal diseases.
Materials and methods
This systematic review was conducted in 2024. Before conducting the research, ethics approval was obtained from Iran University of Medical Sciences (IR.IUMS.REC.1402.192).
Eligibility criteria
In this study, all papers which focused on developing and using CDSS in corneal diseases were searched until end of September 2024. To include articles, they should be published in English with a full-text available and relevant to the aim of the study. Review articles, letters to the editor, protocols, articles in languages other than English, and articles whose full texts were not available were excluded from the study.
Information sources
To retrieve relevant articles, PubMed, Web of Knowledge, Scopus, the Cochrane Library, IEEE Xplore, ProQuest databases, as well as Google Scholar search engine were searched. In addition, the OpenGrey database was searched to find any relevant grey literature. The search process was carried out with reference checking and citation tracking, and all relevant articles were examined.
Search strategy
In order to develop a search strategy, MeSH Terms (Medical Subject Headings) such as clinical decision support system, computer assisted diagnosis, clinical decision-making, computer assisted decision making, anterior eye segments, and cornea were used. Search strategies in different databases are presented in Appendix I.
Selection process
The screening process was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. After retrieving relevant articles, reference management was conducted using EndNote software (version X7), and duplicate items were removed. Titles, abstracts, and full texts of the retrieved studies were screened. The initial search and screening processes were conducted by one of the authors (FE). Then, the remaining articles were independently screened and evaluated by other authors (HA). Any discrepancies were resolved via discussion with the third author (KZ).
Data collection process
Data were extracted using a data extraction form that included the name(s) of author(s), year of publication, country, research objective, research methodology, system characteristics, evaluation criteria, and a summary of the findings. The first author (FE) initially collected the data, and the reports were independently reviewed by other researchers. In case of any disagreement, researchers discussed the issue and resolved it through consensus.
Data elements
In this study, the characteristics of the designed systems, as well as the methodologies used to evaluate these systems were examined and compared in various studies.
Quality and risk of bias assessment
Since the selected articles aimed at diagnosing diseases or addressing corneal problems in patients, and included various qualitative, quantitative, and mixed-methods studies, the Mixed Methods Appraisal Tool (MMAT) was used to assess quality of these articles. This checklist consists of two general questions and five sections, each containing five questions for qualitative studies, quantitative randomized controlled trials, quantitative nonrandomized studies, quantitative descriptive studies, and mixed-methods studies. The responses to the questions include Yes, No, Can't tell, and Comments. 24 The MMAT results were deemed acceptable, allowing inclusion of identified studies, as no articles presented low quality or high risk of bias. Moreover, a checklist from the Joanna Briggs Institute (JBI) was used to assess the risk of bias in the selected studies. This checklist consisted of eight questions, and each question had four options: Yes, Unclear, No, and Not Applicable. 25 The assessment was independently conducted by two researchers (FE and HA).
Synthesis methods
After extracting the necessary data using the data collection form, the results were categorized and reported descriptively. To summarize data, tables were developed based on the data extraction form, and the results were synthesized narratively. As different systems were developed and evaluated, it was not possible to conduct a meta-analysis. Therefore, the system characteristics and evaluation methodologies were described.
Results
Study selection
Initially, 279 articles were identified, and 39 duplicate records were removed. The remaining papers were 240 which were examined in terms of their title and abstract relevancy with the aim of the current study. In this process, 209 irrelevant papers were removed and 31 papers remained to get access to their full texts. There was no access to the full texts of three articles and they were excluded. Then, the full texts of 28 remaining articles were fully reviewed, and some papers were excluded. The main reasons for excluding papers were as follows: the CDSS was not developed (

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram.
Study characteristics
The findings indicated that the selected studies were conducted between 1994 and 2022 in Iran, 18 the United States,14,23 Ukraine, 12 India, 19 Lebanon, 15 Spain, 21 and Singapore. 22
The main objective of these studies was diagnosing and determining the severity of dry eye, 18 identifying patients for low vision rehabilitation, 14 identifying extraocular muscle pathology in patients with strabismus, 12 diagnosing anterior segment eye abnormalities, 19 grading and mapping corneal haze, 15 diagnosing red eye, 21 automatic grading of nuclear cataract, 22 and differentiating keratoconus patterns from other conditions. 23 A summary of the selected papers is presented in Table 1.
A summary of the selected papers.
Quality and risk of bias assessment in the studies
The results of quality and risk of bias assessment are presented in Tables 2 and 3. According to the results, most of the studies were acceptable in terms of quality and had a low risk of bias.
Quality assessment of articles using MMAT
Risk of bias assessment
Results of individual studies
System development
Two main approaches were used to develop CDSS. In the studies conducted by Ebrahimi et al., Guo et al., and López et al. the relationships between variables were first identified using If-Then rules (conditional statements used in logic and programming, and consist of two parts: the “if” part (antecedent) states a condition, and the “then” part (conclusion) specifies an action or result that follows if the condition is met). Subsequently, the coding was completed and the final system was developed.14,18,21 However, in other studies, an image processing methodology was used to develop the system.12,15,19,22,23 The designed systems were either passive (the system operated independently and there was no need for the user to wait) or active (the user directly interacted with the system and had to wait to get feedback to continue working with the system). The results showed that a passive system was used only in one study, 14 and other systems worked actively.12,15,18,19,21–23
In addition, three studies designed knowledge-based systems, as the relationships between variables (independent and dependent) were established according to the opinions of corneal specialists, 18 experts 14 and guidelines.14,18,21 The other five systems were not knowledge-based, but simply identified patterns based on the trained data.12,15,19,22,23
System evaluation
Except one study, 12 other studies evaluated the clinical decision support system. Evaluation was performed through investigating users’ opinion about usefulness and user interface14,21 or comparing final diagnoses, 18 images17,19 and videos 23 with the system performance. The accuracy, sensitivity, and specificity of the system developed for dry eye were 96.9%, 97.5%, and 93.7%, respectively. Moreover, the system's performance and the opinions of corneal specialists were compared using Kappa statistics, demonstrating very good agreement. 18 In Guo et al.'s study, the system performance, ease of use, and usefulness were evaluated. For performance evaluation, the focus was on the accuracy of alerts firing, and false positive (0.2%) and negative rates (5.6%) were calculated. Eight physicians found alerting and working with the system easy, and twelve were interested in using the system. 14 Mahesh Kumar and Gunasundari evaluated their system using 228 eye images, and reported system accuracy (96%), sensitivity (97%), and specificity (99%). 19
For corneal haze detection system, a paired t-test was used to compare the haze intensity and area at different times. The overall corneal clarity significantly increased from 43.4% initially to 50.2% at 1 month, 47.9% at 3 months, and 46.4% at 6 months. 15 In the study conducted by López et al. OphthalDSS was able to diagnose more than 30 anterior segment eye diseases, and most students agreed that the developed system worked well, provided reliable information, was understandable, and had a suitable user interface. 21
Li et al. evaluated the AGNC system using 5850 slit-lamp images and compared the automatic AGNC system grades with the grader's grading results. The success rate was 96.9% for determining lens location and 95% for detecting lens structure. Furthermore, the result of a paired t-test between the automatic grading system and the human grader demonstrated a strong agreement between these two. 23
Maeda et al. used a videokeratoscope to evaluate their automated system against discriminant analysis on 100 corneas with various diagnoses. In discriminant analysis, the sensitivity, specificity, and accuracy of keratoconus detection system were 68%, 99%, and 90%, respectively. For the automated system, the sensitivity, specificity, and accuracy were 89%, 99%, and 96%, respectively. Sensitivity with the automated system classifier (89%) was significantly better than the sensitivity with discriminant analysis (68%). 23
Results of syntheses
Due to the importance of corneal diseases and the possibility of vision loss in case of the late intervention or misdiagnosis, the use of CDSS has been suggested to help ophthalmologists, optometrist, and other eye care professionals to diagnose diseases as soon as possible and prevent patients serious conditions at the later stages of disease progression. The evaluation results of several studies also showed that these systems were successful in accurate diagnosis. According to the results, in addition to several clinical parameters, the analysis of eye images can be helpful for accurate diagnosis. Therefore, it seems that future CDSSs can use the potentials of artificial intelligence (AI) and imaging informatics to analyze eye images and facilitate making decisions by eye care providers.
Discussion
In this research, articles related to the use of CDSS in corneal diseases were reviewed. Although the number of studies which met the inclusion criteria was limited, the results indicated that the system characteristics as well as the method of system development and evaluation were different. The designed systems were mainly developed to support clinical diagnosis, were either active or passive, and divided into the knowledge-based or non-knowledge-based systems. The input and output variables were also different based on the main purpose of system development. Apart from differences, using these systems could improve accuracy, sensitivity and specificity of diagnosis, and users were satisfied with using these systems in clinical decision making.
The results showed that most of the systems were designed to assist making the right diagnosis and screening patient condition. Moreover, in most studies, the system was developed to facilitate diagnosing one12,15,18,22,23 or multiple corneal diseases.19,21 However, in one study, the focus was on diagnosing and referring visually impaired individuals to the rehabilitation services. 14 It should be noted that different types of CDSS are responsible for various tasks, such as presenting clinical guideline, generating documentation templates, computerized alerts and reminders, diagnostic support, management support, and contextually relevant reference information. Many systems can be developed and used for each task in different areas of eye care to improve healthcare quality. 26 CDSSs are also effective in managing diseases that frequently lead to medical visits and directly impact quality of life, such as ocular morphological pathology. 21
In terms of active or passive performance, most studies designed an active system, and only one study developed a passive system. 14 In fact, active systems help users to be informed about doing the right things automatically, and this approach is much more effective than using passive systems, in which users need to inquire about the correct things to do. The active CDSS works in real-time and requires more accurate design with special focus on the details, which might be very essential. However, these systems may also generate too many false-positive alerts, which can be annoying. In addition, passive CDSS require more users’ effort, and users must make a specific query to request advice. 27
Moreover, some systems were knowledge-based,14,18,21 and some others were non-knowledge-based systems.12,15,19 In knowledge-based systems, IF-THEN rules are generated, and the system uses data to evaluate the rules, and producing an output or a recommendation. Rules can be made using literature, best practices, or evidence. Those CDSSs that are non-knowledge-based require a data source, but it is based on AI, machine learning (ML), or statistical pattern recognition. While the use of non-knowledge-based system is increasing, there are still concerns over the accuracy of decisions made by these systems. 26 However, due to the advancement of AI, it is expected that the future CDSSs do not use a knowledge base and rely on the computational analysis.
In three studies, the clinical decision support systems were developed using the MATLAB software environment,8,19,22 while in other studies, the systems were development using other languages and environments.12,14,15,21–23 In fact, a specific programming language is chosen based on the suitability of it for certain tasks or specific operating systems. 27
The system inputs included both numerical/textual data14,18,21 and images.12,15,19,22,23 A variety of data input indicated that there are many opportunities for system development in the future and AI can be used to facilitate this process. Clinical data in the form of unstructured text, images, or signals are remained unexplored and could be potentially used to develop effective CDSS. The use of multi-type clinical data in a CDSS is another area of research which is worth investigation. 28 Regarding the CDSS for corneal diseases, it seems that in addition to signs and symptoms, eye images are helpful for diagnosis and future systems can be developed by using different types of data.
In order to evaluate CDSSs, either the real data were used,15,18,19,22,23 the system results were compared to the physicians’ opinions in the patient records, or users’ perspectives were investigated. The evaluation results might be presented quantitatively and qualitatively. Overall, the system evaluation results were satisfactory, and users evaluated the system as useful, reliable, and effective tools.14,21 The evaluation of a CDSS should validate its efficacy, safety, usability, reliability and reproducibility. However, validation methods vary depending on the type of CDSS and its purpose. The value of a CDSS should also be considered in terms of its long-term implications and the need to improve it based on new research findings and discoveries. 24
Overall, it seems that the use of CDSS in corneal diseases may have received less attention compared to other eye diseases. Therefore, with respect to the advancement of technology, it seems that future research can be directed to use new technologies such as AI to examine the effectiveness of the new systems in terms of reducing the rates of misdiagnosis and improving patient outcomes.
Research limitations
Although a comprehensive search was conducted in six databases as well as Google Scholar, there might be papers that were not included in the current study. These papers might not be in English, their full texts were not available, were indexed in other databases, or were published after submitting the current study. Moreover, mobile-based applications were not considered in this research, as they may not be specifically developed for corneal diseases. Future research can focus on investigating the applications of other computer-aided tools for diagnosing different eye diseases.
Conclusion
In this study, the use of clinical decision support systems in corneal diseases was investigated. These systems were mainly developed to aid diagnosis and included active/passive, knowledge-based and non-knowledge based systems. In addition, different methodologies were used to evaluate their performance. The results showed that the use of CDSS in ophthalmology aided in disease diagnosis and improved quality of patient care services. As the number of the retrieved studies related to corneal diseases was quite limited, it seems that further research can contribute to improve the use of CDSS in teleophthalmology, referral refinement, and resource management especially in deprived geographical areas with a focus on corneal diseases. This can help patients and healthcare providers to make more efficient decisions, and can improve quality of care.
Supplemental Material
sj-docx-1-dhj-10.1177_20552076241303805 - Supplemental material for A systematic review of using clinical decision support systems in corneal diseases
Supplemental material, sj-docx-1-dhj-10.1177_20552076241303805 for A systematic review of using clinical decision support systems in corneal diseases by Farzad Ebrahimi, Haleh Ayatollahi and Kimia Zeraatkar in DIGITAL HEALTH
Supplemental Material
sj-docx-2-dhj-10.1177_20552076241303805 - Supplemental material for A systematic review of using clinical decision support systems in corneal diseases
Supplemental material, sj-docx-2-dhj-10.1177_20552076241303805 for A systematic review of using clinical decision support systems in corneal diseases by Farzad Ebrahimi, Haleh Ayatollahi and Kimia Zeraatkar in DIGITAL HEALTH
Footnotes
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