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      Keratoconus Diagnosis and Treatment: Recent Advances and Future Directions

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          Abstract

          Keratoconus is a disorder characterized by progressive corneal thinning and steepening that may result in significant visual impairment secondary to high astigmatism, corneal scarring, or even corneal perforation. Early detection and screening of keratoconus are essential for effective management and treatment. Several screening methods, such as corneal topography and tomography, corneal biomechanics, and genetic testing, are being developed to detect keratoconus at an early stage. Once detected, prevention of progression is the mainstay of keratoconus management. Corneal collagen cross-linking is a minimally invasive treatment option that can slow or halt the progression of keratoconus. Additionally, recent studies have investigated the potential use of copper sulfate eye drops (IVMED-80) and extracellular vesicles to prevent the progression of keratoconus as non-invasive treatment options. For visual rehabilitation, currently available treatments include scleral lenses, intracorneal ring segments, corneal allogenic intrastromal ring segments, and deep anterior lamellar keratoplasty. The safety and efficacy of these emerging treatment options for keratoconus are currently being investigated.

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          Exosomes in cancer development, metastasis, and immunity

          Lin Zhang, Dihua Yu (2019)
          Exosomes play essential roles in intercellular communications. The exosome was discovered in 1983, when it was found that reticulocytes release 50-nm small vesicles carrying transferrin receptors into the extracellular space. Since then, our understanding of the mechanism and function of the exosome has expanded exponentially that has transformed our perspective of inter-cellular exchanges and the molecular mechanisms that underlie disease progression. Cancer cells generally produce more exosomes than normal cells, and exosomes derived from cancer cells have a strong capacity to modify both local and distant microenvironments. In this review, we summarize the functions of exosomes in cancer development, metastasis, and anti-tumor or pro-tumor immunity, plus their application in cancer treatment and diagnosis/prognosis. Although the exosome field has rapidly advanced, we still do not fully understand the regulation and function of exosomes in detail and still face many challenges in their clinical application. Continued discoveries in this field will bring novel insights on intercellular communications involved in various biological functions and disease progression, thus empowering us to effectively tackle accompanying clinical challenges.
          Article 0 comments Cited 395 times – based on 0 reviews     Review now
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            Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9

            Mathilde Mathieu, Nathalie Nevo, Mabel Jouve … (2021)
            Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and their secretion mechanisms are not fully characterized: how and to what extent EVs form as intraluminal vesicles of endocytic compartments (exosomes), or at the plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking of the EV markers CD9 and CD63 from the endoplasmic reticulum to their residency compartment, respectively PM and late endosomes. We observe transient co-localization at both places, before they finally segregate. CD9 and a mutant CD63 stabilized at the PM are more abundantly released in EVs than CD63. Thus, in HeLa cells, ectosomes are more prominent than exosomes. By comparative proteomic analysis and differential response to neutralization of endosomal pH, we identify a few surface proteins likely specific of either exosomes (LAMP1) or ectosomes (BSG, SLC3A2). Our work sets the path for molecular and functional discrimination of exosomes and small ectosomes in any cell type. Extracellular vesicles (EVs) play a role in intercellular communication, however the precise biogenesis of different populations of EVs are not clear. Here, the authors follow the intracellular trafficking of two proteins before their secretion in EVs and report the biogenesis and protein markers of EV subtypes: ectosomes budding from the plasma membrane as well as exosomes from late endosomes.
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              Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus.

              Gregor Wollensak, Eberhard Spoerl, Theo Seiler (2003)
              In animal eyes, a significant increase in corneal biomechanical stiffness has been found after collagen crosslinking by combined riboflavin/ultraviolet-A (UVA) treatment. The aim of the present study was to evaluate the clinical usefulness of riboflavin/UVA-induced collagen crosslinking for bringing the progression of keratoconus to a halt. Prospective, nonrandomized clinical pilot study. Twenty-three eyes of 22 patients with moderate or advanced progressive keratoconus (maximum K value, 48-72 diopters) were included. After central corneal abrasion, photosensitizing riboflavin drops were applied and the eyes exposed to UVA (370 nm, 3 mW/cm(2)) in a 1-cm distance for 30 minutes. Postoperative examinations were performed in 6-month intervals, including visual acuity testing, corneal topography, slit-lamp examination, measurement of endothelial cell density, and photographic documentation. The follow-up time was between 3 months and 4 years. In all treated eyes, the progression of keratoconus was at least stopped. In 16 eyes (70%) regression with a reduction of the maximal keratometry readings by 2.01 diopters and of the refractive error by 1.14 diopters was found. Corneal and lens transparency, endothelial cell density, and intraocular pressure remained unchanged. Visual acuity improved slightly in 15 eyes (65%). Collagen crosslinking may be a new way for stopping the progression of keratectasia in patients with keratoconus. The need for penetrating keratoplasty might then be significantly reduced in keratoconus. Given the simplicity and minimal costs of the treatment, it might also be well-suited for developing countries. Long-term results are necessary to evaluate the duration of the stiffening effect and to exclude long term side-effects.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Ophthalmol
                Journal ID (iso-abbrev): Clin Ophthalmol
                Journal ID (publisher-id): opth
                Title: Clinical Ophthalmology (Auckland, N.Z.)
                Publisher: Dove
                ISSN (Print): 1177-5467
                ISSN (Electronic): 1177-5483
                Publication date (Electronic): 16 September 2023
                Publication date Collection: 2023
                Volume: 17
                Pages: 2705-2718
                Affiliations
                [1 ]Department of Ophthalmology, University of California San Francisco , San Francisco, CA, USA
                [2 ]School of Medicine, University of California San Francisco , San Francisco, CA, USA
                [3 ]Francis I. Proctor Foundation, University of California San Francisco , San Francisco, CA, USA
                Author notes
                Correspondence: Maanasa Indaram, Wayne and Gladys Valley Center for Vision, UCSF Department of Ophthalmology , 490 Illinois Street, San Francisco, CA, 94158, Tel +1 415 476-2896, Email Maanasa.Indaram@ucsf.edu
                Author information
                http://orcid.org/0000-0002-2327-5221
                http://orcid.org/0000-0001-6228-3307
                Article
                Publisher ID: 392665
                DOI: 10.2147/OPTH.S392665
                PMC ID: 10511017
                PubMed ID: 37736107
                SO-VID: 01219106-1126-4203-a177-192424607928
                Copyright © © 2023 Bui et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 06 June 2023
                Date accepted : 07 September 2023
                Page count
                Figures: 5, References: 101, Pages: 14
                Categories
                Subject: Review

                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: keratoconus,corneal cross-linking,intracorneal ring segments,deep anterior lamellar keratoplasty,ivmed-80,extracellular vesicles
                Data availability:
                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: keratoconus, corneal cross-linking, intracorneal ring segments, deep anterior lamellar keratoplasty, ivmed-80, extracellular vesicles

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