In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to those of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, as well as proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.

/pdf/in-vivo-confocal-microscopy-of-corneal-nerves-in-health-and-hnxunvo6by.pdf

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

Background
Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears.

Objectives
To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo.

Search methods
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches.

Selection criteria
This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy.

Data collection and analysis
We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text.

Main results
We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias.

Authors' conclusions
OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.

/pdf/over-the-counter-otc-artificial-tear-drops-for-dry-eye-48paxdm3x5.pdf

Over the counter (OTC) artificial tear drops for dry eye syndrome

Efron, N., Jones, L., Bron, A. J., Knop, E., Arita, R., Barabino, S., … Markoulli, M. (2013). The TFOS International Workshop on Contact Lens Discomfort: Report of the Contact Lens Interactions With the Ocular Surface and Adnexa Subcommittee. Investigative Opthalmology & Visual Science, 54(11), TFOS98. https://doi.org/10.1167/iovs.13-13187

/pdf/the-tfos-international-workshop-on-contact-lens-discomfort-5gf0zhoyjl.pdf

The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens interactions with the ocular surface and adnexa subcommittee.

Vital dye staining has been used for over a century to assess the severity of ocular surface disease. However, despite common usage, a universally accepted "gold standard" grading scale does not exist for corneal and conjunctival staining, which can impact the ability to diagnose and monitor ocular surface conditions such as dry eye. The Food and Drug Administration (FDA) and other international regulatory agencies rely on ocular surface staining as a primary endpoint for new drug approvals, so that absence of a "gold standard" scale may affect approval of new drug treatments. To begin to address this problem, we review existing, published grading scales in an integrated fashion, highlighting their differences and similarities to emphasize common themes and the methods and elements that are important in creating a standardized scale. Our goal is to aid the field in moving towards an accepted standardized grading scale for ocular surface staining that can be applied in clinic and research settings for a variety of ocular conditions.

Review and analysis of grading scales for ocular surface staining.

An objective, digital-imaging method of measuring corneal staining was evaluated in 24 subjects wearing soft contact lenses. The method was used to compare the clinical performance of common multipurpose care systems (MPS) for soft contact lens care. Subjects used three different MPS, one containing polyquaternium-1 (PQ) and two containing polyhexanide (PX1 and PX2), for 2 weeks in a randomised, single-masked (investigator) crossover study. Corneal staining induced with the three MPS was analysed using an image-processing program (ImageTool, UTHSCSA Version 2, University of Texas, USA). Conjunctival hyperaemia and papillae were also evaluated. The intraclass correlation coefficient was similar with image analysis to that of investigator grading (0.876, 0.879, respectively). Significant differences in staining response were detected using the objective method. There was significantly less staining area with polyquaternium-1 (PQ) than polyhexanide (PQ: 0.12 mm2, PX2: 0.91 mm2). Inferior palpebral papillae were significantly greater with PX2 than with PQ (1.0, 0.7 (0–4), respectively). The technique was shown to be an effective method of evaluating different corneal staining responses. Bilateral corneal staining in three or more quadrants is useful in the diagnosis of MPS-related staining.

Subjective and objective measures of corneal staining related to multipurpose care systems

Purpose. To compare live and photographic (still) grades of corneal staining of the same eyes and the repeatability ofgrading between two investigators.Methods. Thirtypatientswererecruitedtoparticipateinacontactlensstudy,andtheirlevelofcornealstainingwasgradedbytwoinvestigatorsinsitu(liveimages),usingslitlampbiomicroscopy.Digitalstillimagesofthecornealstainingwerealsocaptured during the study visits. An independent observer selected 105 of the still images graded by investigator 1 andanother 105 images graded by investigator 2 and presented them to the original investigator in a random order, on threeseparateoccasions.Gradingwasperformedatthetimeofthelivegradingandthethreestillimagesessions,usingtheCentreforContactLensResearchcornealstainingscalethatcombinesgradesofbothextentandtypetoprovideanoverall‘‘globalstaining score’’ from 0 to 10,000 for corneal staining. A comparison was made between live and still grades as well as theintrainvestigator repeatability for the multiple grading of the still images.Results. The mean (TSD) of corneal staining grades recorded for the same eyes examined live and then later on threeoccasionswas1795 (T1083) and714 (T974),respectively,forparticipantsexaminedbyinvestigator1(pG0.001)and1854(T1075) and 461 (T411) for those examined by investigator 2 (p G 0.001). There was a significant difference over the threerepeated still grading sessions for each investigator (p G 0.001), although there was a high degree of consistency among thethree still grading sessions for each of the investigators: the intraclass correlation for investigator 1 was 0.91 (confidenceinterval, 0.87 to 0.93) and that for investigator 2 was 0.82 (confidence interval, 0.77 to 0.87).Discussion. Digital still image grading of corneal staining significantly underrepresented the amount of corneal stainingobserved through a slit lamp. Clinical investigators graded corneal staining with a high degree of consistency.(Optom Vis Sci 2015;92:00Y00)Key Words: corneal staining, corneal grading, repeatability of grading, slit lamp grading, photographic grading

Comparison between Live and Photographed Slit Lamp Grading of Corneal Staining

Confocal microscopy and optical coherence tomography imaging of hereditary granular dystrophy

Purpose Corneal vasculature change in contact lens wearers has been linked to the level of hypoxia within the cornea.To assess the impact a treatment has on limbal vessels, a sensitive method of measurement and quantification is required. Methods A group of 21 highly myopic, hydrogel wearers, with preexisting signs of corneal hypoxia, were enrolled into a study where they wore sifilcon A penetrated hydrogel lenses (Dk/t ± 117), on a daily wear basis for 9 months. At all scheduled visits, photographs were taken of the superior, inferior, temporal, and nasal limbal regions which were then imported into Adobe Photoshop. A red-free filter was applied to enhance the contrast of the blood columns. In each quadrant, the length of the longest visible blood column was measured and the blood columns that penetrated 0.5 mm into the cornea were counted. A control group of 11 non-lens wearers was recruited. Their photographs were taken at the beginning of the study and 9 months later. An independent, masked observer assessed the photographs. Results There was a significant decrease in the maximum penetration of the blood column in all quadrants (p = 0.001) from baseline to the 9-month visit (e.g., superior: baseline 0.84 ± 0.39 mm; 9 months 0.63 ± 0.20 mm). There was also significant reduction in the number of visible blood columns longer than 0.5 mm in each quadrant (p = 0.001) from baseline to 9 months in all quadrants (e.g., superior: baseline 14.0 ± 8.2; 9 months 6.5 ± 6.0). The control group showed no change over time for the maximum blood column length (p = 0.638) or the number of columns 0.5 mm (p = 0.341). Conclusions A group of highly myopic subjects exhibited reduction in the maximum length and number of blood columns in the cornea when ref it with a highly permeable silicone hydrogel material. The use of photography, along with Adobe Photoshop software, provides a reliable way of measuring corneal vascular responses over time.

Use of a photographic manipulation tool to assess corneal vascular response.

Hyper-reflective cells observed by confocal microscopy as an indicator of lens and lens care interactions

Repeatability of Normalized Light Scatter of the Cornea Determined Using Optical Coherence Tomography (OCT)

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

S. Schneider

Author Tools

Chat about Author