Eye Disease Research Research Articles

Building a framework for public and patient involvement in dry eye disease research. A case study

Aims/Purpose: This study aims to improve bidirectional communication strategies between patients/public, preclinical researchers, and clinical experts to address the lack of effective public and patient involvement (PPI) in preclinical vision research, aiming to refocus research on actual patient needs.Methods: An international team conducted multiple PPI activities, including a critical review on PPI in preclinical ocular research1, World‐café workshops, patient interviews, structured surveys, and round‐table discussions. Dry Eye Disease's wide clinical presentation and impact on daily life were explored. Patient experiences were shared to better understand their needs, increase research value, awareness, and advocacy.Results: Activities highlighted the need for incorporating PPI in ocular research at the preclinical stage. Recurrent themes were identified across patients and researchers. From 20 patient interviews and 50 surveys, 82% responded that they received most information from clinical spaces and were unaware of current research.2 Patients did not know how to become involved in PPI. In a PPI Training Course, 19 preclinical researchers agreed on the need for clearer PPI guidelines and training.Conclusions: PPI activities emphasized DED's severe impact on QoL and the need for new treatments. Round‐table discussions fostered connections and deeper understanding of DED, shifting researchers' focus to unmet patient needs. Further integration of PPI into preclinical research will benefit both researchers and patients. This multimodal PPI approach can benchmark incorporating patient perspectives in preclinical ocular research. Next steps – with patients, create a tool kit for communications skills development for pre‐clinical researchers.References Ames T, Matthews E, Reynolds A et al. How patient/public involvement impacts the research journey – an overview of the visual impairment research field, Open Res Europe 2023, 3: 135. https://doi.org/10.12688/openreseurope.16057.1. Ames T, Matthews E, Reynolds A et al. ARVO. 2024. Dry Eye Disease as a case study to understand the public and patient involvement gap in lab‐based preclinical vision research using interdisciplinary approaches [Poster].

A Bibliometric Analysis of Pregnancy-Related Eye Disease from 1999 to 2022.

This systematic review and bibliometric analysis investigated the keywords appearing most in the pregnancy-related eye disease field to elucidate the current state and trends of pregnancy-related eye disease research. A systematic literature analysis of pregnancy-related eye disease was performed using the Web of Science Core Collection (WOS) databases. We used the keywords "ocular" OR "eye*" and "pregnancy" OR "pregnant" OR "gestation" to search for articles published from 1999 to 2022. Study data were analyzed and visualized using VOSviewer and CiteSpace. We analyzed 929 articles published from 1999 to 2022. From 1999 to 2012, the article number increased slowly, with a marked acceleration in publication frequency after 2013, original papers accounted for 780 (84%) of the total number of articles published. David A. Mackey was the most prolific writer, and Margaret A. Honein contributed the most citations. The American Journal of Ophthalmology, PLOS One, and the European Journal of Ophthalmology published the most articles. The American Journal of Ophthalmology, Ophthalmology, British Journal of Ophthalmology, Investigative Ophthalmology and Visual Science were the four most commonly cited journals. The University of Western Australia, the University of Sao Paulo, and the University of Melbourne were highly prolific institutions. Five co-cited references had a citation burst up to 2022, analyzed by CiteSpace. Keyword analysis (VOSviewer) yielded recent key themes (pregnancy, women, eye, risks and diagnosis) and suggested future research directions. The current results laid the foundation of bibliometrics for scholars and identified researchers, scientific journals, countries, keyword clustering, hot topics, and trends in the literature. High-impact-factor journals contain the most keyword-clustering research and open new horizons for research in the pregnancy-related eye disease nursing field, providing research inspiration for investigators in this field.

TraceEyeDisease: a web-based database for investigating trace elements and their imbalances in eye diseases

Eye diseases remain a significant global health concern, with trace elements crucial in maintaining ocular health and preventing ocular disorders. In ocular health, trace elements have been recognized as critical factors influencing the development and progression of multiple eye diseases. In this study, we conducted a thorough literature search through PubMed to acquire data concerning different eye diseases associated with trace elements. These diseases are essential in trace element imbalances or deficiencies in their progression. Our approach included a meticulous compilation of information from various databases, systematically integrated into a carefully curated database. In total, we identified 178 distinct genes that encode proteins linked to fourteen trace elements in this comprehensive list. A web-based database designed to formulate evidence-based hypotheses regarding the impact of trace element deficiency and imbalance on eye diseases was presented using Shiny R. This study underscores the vital role of trace elements in preserving ocular health. The Shiny R application facilitates subsequent investigations, fostering enhanced insights into public health, clinical practices, and eye disease research. The URL of TraceEyeDiseas is https://tredis.shinyapps.io/TraceEyeDisease/.

Current Advances in Single-Cell RNA Sequencing in Diabetic Retinopathy

With the development of high-throughput sequencing technology, humans have been able to conduct large-scale analysis of DNA sequence, chromatin structure, RNA transcripts, proteins, metabolites and other genomes and their products. Traditional high-throughput transcriptome sequencing techniques based on tissue samples (RNA Seq) are used to centrally sequence thousands of cells, each of which varies in size, protein levels, and mRNA expression transcription. Measuring the average of multiple cells grouped together can mask significant differences in gene expression between cells. Single-cell RNA sequencing is a technique for high-throughput sequencing of the genome, transcriptome, and epigenome at the single-cell level. Based on the single cell RNA transcription map, the intraocular cells can be distinguished from other subtypes, and the different subtypes are found to have significant differences in morphology, physiology and specific expression genes. In recent years, the application of single-cell RNA sequencing technology in the field of ophthalmology has increased, mainly including cell type and cell subtype identification, retinal development process, and eye disease research. This paper systematically summarized the latest application of single-cell sequencing technology in the field of diabetic retinopathy, and summarized marker genes and potential therapeutic targets. It has guiding significance for the clinical treatment of diabetic retinopathy.

Global trends in diabetic eye disease research from 2012 to 2021.

JOURNAL/nrgr/04.03/01300535-202410000-00032/figure1/v/2024-02-06T055622Z/r/image-tiff Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries--the United States, China, Japan, the United Kingdom, Spain, Germany, and France--by searching for all global diabetic eye disease journal articles in the Web of Science and PubMed databases, all global registered clinical trials in the ClinicalTrials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority (89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema (9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development (58.19%). Approximately half of the trials (49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic (40 out of 1830; 2.19%) and diabetic eye disease (3 out of 1830; 0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

Dry eye disease knowledge deficit

Lucy Patchett summarises recent dry eye disease research that spotlights lack of public awareness and knowledge

Impact of Lacrimal Gland Extraction on the Contralateral Eye in an Animal Model for Dry Eye Disease.

PurposeAlthough there is still no consensus on the best animal model for dry eye disease research, a model based on lacrimal gland extraction (LGE) model is widely used. In this study, we aimed to investigate the histopathological changes taking place on the contralateral eye after unilateral LGE to determine whether it is useful as a control.MethodsSeven-week-old male C57BL/6 mice were divided into naive control, environmental chamber model, and LGE groups. Corneal fluorescein staining was scored to quantify the severity of damage. Morphological changes in the cornea, conjunctiva, and lacrimal gland (LG) were determined by hematoxylin and eosin staining and compared to those on naive control animals.ResultsCompared to naive subjects, the unilateral LGE model showed enhanced corneal erosion scores and loss of conjunctival goblet cells, not only on the ipsilateral but also on the contralateral side. These changes in the ocular surface became more pronounced in a time-dependent manner. Furthermore, loss of LG acinar cells and leukocyte infiltration were detected in the contralateral LGs of the LGE model.ConclusionsConsidering the changes observed in the ocular surface and LGs, the contralateral side of the LGE model may not offer proper control conditions for the experimental comparison of the effects of dry eye disease in vivo. There may be regulatory feedback or crosstalk system between both eyes activated in response to LGE.

An Exploratory Study to Investigate the Utility of Clinical Screening for Neurodegenerative Disease in Age-Related Eye Disease Research.

Unrecognized neurodegenerative diseases (NDD) in age-related eye disease research studies have the potential to confound vision-specific quality of life and retinal optical coherence tomography (OCT) outcome measures. The aim of this exploratory study was to investigate relationships between NDD screening tools and visual outcome measures in a small cohort of controls from the Colorado Age-Related Macular Degeneration Registry (CO-AMD), to consider the utility of future studies. Twenty-nine controls from the CO-AMD were screened using the Montreal Cognitive Assessment (MoCA), a Colorado Parkinsonian Checklist, and the Lewy Body Composite Risk Score. Univariate and multivariable linear regression modeling was used to assess associations between screening tools and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and macular OCT outcome measures, and t tests were used to evaluate outcome measure differences between those with normal vs abnormal MoCA scores. One patient withdrew. The average age was 72.8 years, and 68% were female patients. Ten participants (36%) had abnormal MoCA scores, and their VFQ-25 scores were only 1 point less and not statistically different than those with normal MoCA scores. Macular OCT volumes and thicknesses for retinal nerve fiber layer (RNFL) and retinal ganglion cell layer were consistently and moderately lower for those with abnormal MoCA scores, and a positive association between MoCA and macular RNFL volume was observed, although differences and regression were not significant. Parkinson screening tests were abnormal for only 4 participants and were not associated with OCT or VFQ-25 measures by regression modeling. Given the degree and direction of observed differences, further investigation is warranted regarding the relationship between cognitive screening tools and macular OCT measures in age-related eye disease research, but future investigations regarding the relationship between NDD screening tools and VFQ-25 seem unwarranted.

Blind Source Separation of Retinal Pulsatile Patterns in Optic Nerve Head Video-Recordings.

Dynamic optical imaging of retinal hemodynamics is a rapidly evolving technique in vision and eye-disease research. Video-recording, which may be readily accessible and affordable, captures several distinct functional phenomena such as the spontaneous venous pulsations (SVP) of central vein or local arterial blood supply etc. These phenomena display specific dynamic patterns that have been detected using manual or semi-automated methods. We propose a pioneering concept in retina video-imaging using blind source separation (BSS) serving as an automated localizer of distinct areas with temporally synchronized hemodynamics. The feasibility of BSS techniques (such as spatial principal component analysis and spatial independent component analysis) and K-means based post-processing method were successfully tested on the monocular and binocular video-ophthalmoscopic (VO) recordings of optic nerve head (ONH) in healthy subjects. BSSs automatically detected three spatially distinct reproducible areas, i.e. SVP, optic cup pulsations (OCP) that included areas of larger vessels in the nasal part of ONH, and "other" pulsations (OP). The K-means post-processing reduced a spike noise from the patterns' dynamics while high linear dependence between the non-filtered and post-processed signals was preserved. Although the dynamics of all patterns were heart rate related, the morphology analysis demonstrated significant phase shifts between SVP and OCP, and between SVP and OP. In addition, we detected low frequency oscillations that may represent respiratory-induced effects in time-courses of the VO recordings.

Update on the clinical assessment and management of thyroid eye disease.

To offer an update on advances and controversies in the assessment, investigation and treatment of thyroid eye disease (TED), a disfiguring orbital autoimmune disease, which can manifest with diplopia and threaten not only sight - but also life. Developments in biomarkers and imaging are helping to tailor the management of patients. Emerging therapies target different pathways in the disease and are informed by studies into TED pathogenesis: the last 2 years has, for example, seen the culmination of a two-decade long bench-to-bedside story in which an original focus on the IGF1 receptor has translated into an effective treatment for proptosis in thyroid eye disease. Whether this will result in a real-world reduction in TED-related morbidity will depend on access; commercial pricing decisions may preclude widespread adoption of novel therapies. Thyroid eye disease research is enjoying a renaissance with advances in both monitoring and treatment coupled with a renewed emphasis on a holisitic approach, which includes aesthetic care for patients; this is perhaps the most exciting time to be part of the international thyroid eye disease community in decades - for physicians, surgeons and patients. The commercial window for break-through drugs are narrowing with an array of new therapeutic agents in the pipeline over the coming decade.

Assessment of Orbital Computed Tomography (CT) Imaging Biomarkers in Patients with Thyroid Eye Disease.

To understand potential orbital biomarkers generated from computed tomography (CT) imaging in patients with thyroid eye disease. This is a retrospective cohort study. From a database of an ongoing thyroid eye disease research study at our institution, we identified 85 subjects who had both clinical examination and laboratory records supporting the diagnosis of thyroid eye disease and concurrent imaging prior to any medical or surgical intervention. Patients were excluded if imaging quality or type was not amenable to segmentation. The images of 170 orbits were analyzed with the developed automated segmentation tool. The main outcome measure was to cross 25 CT structural metrics for each eye with nine clinical markers using a Kendall rank correlation test to identify significant relationships. The Kendall rank correlation test between automatically calculated CT metrics and clinical data demonstrated numerous correlations. Extraocular rectus muscle metrics, such as the average diameter of the superior, medial, and lateral rectus muscles, showed a strong correlation (p < 0.05) with loss of visual acuity and presence of ocular motility defects. Hertel measurements demonstrated a strong correlation (p < 0.05) with volumetric measurements of the optic nerve and other orbital metrics such as the crowding index and proptosis. Optic neuropathy was strongly correlated (p < 0.05) with an increase in the maximum diameter of the superior muscle. This novel method of automated imaging metrics may provide objective, rapid clinical information. This data may be useful for appreciation of severity of thyroid eye disease and recognition of risk factors of visual impairment from dysthyroid optic neuropathy from CT imaging.

Application of CRISPR/Cas9 genome editing technology in the research of eye diseases

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is an adaptive immune system against invasive viruses and exogenous DNA, which is developed by bacteria and archaer during long-term evolution.With advances in technology, researchers have found that CRISPR/Cas9 system can precisely edit the genomes of eukaryotic cells through insertion, replacement or deletion of target genes.Using CRISPR/Cas9 genome editing technology, researchers found that overexpression of paired box gene 6 (PAX6) in cornea can cause congenital corneal epithelial damage; this technology promoted the research on the pathogenic mechanism of keratin 12 (KRT12) mutation in Meesmann corneal epithelial dystrophy; it has also built congenital cataract animal models by knocking out the GJA8 gene and αA lens gene, which is beneficial to the application of the diagnosis and pathological analysis of congenital cataract.In addition, the researchers have used CRISPR/Cas9 genome editing technology to confirm the correlation of RHOS334 mutated RHO allele, P23H mutated RHO gene, Y347X mutated Pde6b gene, and mutant RP9 allele with retinitis pigmentosa.The application of this technology has provided evidence to support the association of KCNJ13 gene and mutant CEP290 gene with Leber congenital amaurosis.CRISPR/Cas9 can provide target spot of intraocular neovascular diseases the targeted therapy by editing of VEGFR2 gene and TXNIP gene, and it also playse an important role in the study of pathogenic genes and establishment of animal models for proliferative vitreoretinopathy and retinoblastoma.In this review, we introduced the evolutionary history, the molecular characteristics and the mechanism of CRISPR/Cas9, and summarized its current research advances in eye diseases. Key words: CRISPR/Cas9; Gene editing technology; Eye diseases; Animal disease models; Gene therapy

International publication trends in dry eye disease research: A bibliometric analysis

PurposeTo perform a bibliometric analysis in the field of dry eye disease (DED) research to characterize the current international status of DED research and to identify the most effective actors (journals, countries, authors) involved in this field. MethodsScientometric methods were used to evaluate global scientific production and development trends in DED research, using the Web of Science Core Collection. ResultsThe growth of the literature related to DED averaged 12.18% over the last 10 years. A total of 5522 original and review articles, published in 821 different journals, were identified. The USA was the most productive country with 34.53% of the overall articles studied and 46.10% of the overall citations. The Ocular Surface published a very high percentage of articles related to DED relative to the total number of articles published (31.87%). The most productive institutions and the most frequently cited articles were from the USA and Japan. A network visualization map for country collaboration revealed that most European countries developed most of their collaborations with countries belonging to their own continent, which was not the case for the USA or Japan. A total of 41,956 KeyWords Plus were found with an average of 7.6 (SD = 3.15) KeyWords Plus per article. ConclusionsThis study provides a broad view of the current status and trends in DED research and may help clinicians, researchers and policy makers better understand this research field and predict its dynamic directions.

Trends and topics in eye disease research in PubMed from 2010 to 2014.

Background: The purpose of this study is to provide a report on scientific production during the period 2010–2014 in order to identify the major topics as well as the predominant actors (journals, countries, continents) involved in the field of eye disease. Methods: A PubMed search was carried out to extract articles related to eye diseases during the period 2010–2014. Data were downloaded and processed through developed PHP scripts for further analysis. Results: A total of 62,123 articles were retrieved. A total of 3,368 different journals were found, and 19 journals were identified as “core journals” according to Braford’s law. English was by far the predominant language. A total of 853,182 MeSH terms were found, representing an average of 13.73 (SD = 4.98) MeSH terms per article. Among these 853,182 MeSH terms, 14,689 different MeSH terms were identified. Vision Disorders, Glaucoma, Diabetic Retinopathy, Macular Degeneration, and Cataract were the most frequent five MeSH terms related to eye diseases. The analysis of the total number of publications showed that Europe and Asia were the most productive continents, and the USA and China the most productive countries. Interestingly, using the mean Five-Year Impact Factor, the two most productive continents were North America and Oceania. After adjustment for population, the overall ranking positions changed in favor of smaller countries (i.e. Iceland, Switzerland, Denmark, and New Zealand), while after adjustment for Gross Domestic Product (GDP), the overall ranking positions changed in favor of some developing countries (Malawi, Guatemala, Singapore). Conclusions: Due to the large number of articles included and the numerous parameters analyzed, this study provides a wide view of scientific productivity related to eye diseases during the period 2010–2014 and allows us to better understand this field.

Research of eye diseases associated with PERK mediated endoplasmic reticulum stress

Endoplasmic reticulum is the organelle where proteins get folded and assembled, and all kinds of damage factors can lead to the accumulation of unfolded proteins, therefore initiate endoplasmic reticulum stress (ERS) by activating the intracellular signal transduction pathways-cumulatively called the unfolded protein response, either to protect cells or to induce cell apoptosis. PERK pathway has been considered as a main signal transduction pathway of ERS, and a lot of eye diseases are correlated with PERK pathway mediated ERS. This article mainly summarize the progress of the eye diseases associated with PERK pathway mediated ERS.

Prevention of Age-Related Macular Degeneration–Like Retinopathy by Rapamycin in Rats

Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy.

Pediatric Eye Disease Investigator Group Amblyopia Treatment Review

IntroductionThe Pediatric Eye Disease Investigator Group (PEDIG), formed in 1997, has been dedicated to clinical research of eye diseases affecting children. Over the last three years, PEDIG has studied the efficacy of amblyopia treatment regimes, and has followed the long-term outcomes of these regimes. These studies are known as the Amblyopia Treatment Studies (ATS) and have been sorted into eight categories. Four of these have been published and four are still awaiting publication.MethodA survey of ophthalmologists and orthoptists attending a seminar in British Columbia, Canada. They were questioned as to how they treat amblyopia in light of the PEDIG studies.ResultsNinety percent continue to use patching as their first method of treatment in moderate amblyopia. Over 50% will patch four hours/day or more to begin treatment and 83% will use near exercises to augment the patching. Two thirds will begin patching six or more hours/day in patients with severe amblyopia. Those that use atropine, use it daily rather than on weekends. Most felt that amblyopia could be treated to age 12 years and some thought it could be treated to 14 years.ConclusionMost ophthalmologists and orthoptists taking the survey have not significantly changed their approach to amblyopia treatment in light of the recent PEDIG studies.

General Information &amp; Statistics

Funds for Glaucoma and Eye Disease Research. Diabetes Vaccine Development Center to Open in 2003. Access to Cochrane Online Library for all Australians. China Bans Liver Risk Diet Pill. China's Largest Experimental Animal Breeding Center On the Way. Beijing to Host International Bioscientists Conference. Indonesia and Singapore Join Hands in Vegetable Project. Japanese Survey Yields Vital Heart Attack Data. Japan Urges China to Tighten Control on Diet-pill. Malaysia Sees Rise in Dengue Fever. Eating More Seafood Good for NZ’s Mental Health. Conference on Legal and Business Perspectives in IT and Biotech. Singapore Introduces New Drug to Battle Sepsis. US Praises Singapore's Life Sciences Effort.

Diabetes and thyroid-related eye disease.

During the past year, the results of the Diabetes Control and Complications Trial became available. This event is expected to influence all future diabetes eye disease research. For this reason, this article starts with a discussion of these results.