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Blaser F, Meneau I, Wiedler J, Lamprecht O, Barthelmes D, Zweifel S, Perschak P, Wiest MRJ, Fierz F, Said S, Bajka A. Sterility Assessment of Reclosable Ophtioles with Unpreserved Autologous Serum during Single-Day Use. Klin Monbl Augenheilkd 2025; 242:304-309. [PMID: 40239671 DOI: 10.1055/a-2496-7289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
BACKGROUND According to the European Pharmacopoeia, multidose containers for eye drops must either contain antimicrobial agents, preservatives, or be fitted with filters or non-return valves to prevent microbial contamination after opening. Vials for single-day use do not have filters or non-return valves. The aim of this study is to demonstrate the safety of reclosable vials (ophtioles) containing unpreserved autologous serum eye drops (ASEDs) by evaluating their sterility during single-day use. MATERIAL AND METHODS Two types of reclosable ophtioles were evaluated, one with a screw cap (Meise System, Heinz Meise GmbH, Schalksmühle, Germany) and the other one with a plug cap (COL System, BIOMED DEVICE S. R. L., Modena, Italy). Drop application over 12 hours was simulated in the laboratory following the manufacturer's instructions. For the Meise System, drops were applied at 2-hour intervals, while for the COL System, drops were applied at 1-hour intervals. Each application involved inoculating a chocolate-agar PolyViteX plate (PolyViteX, bioMérieux SA, Marcy-l'Étoile, France) with two drops spaced apart on the same plate and then incubating the plate. After 24 hours, a final inoculation was performed to check for sterility, and the plates were scored after 24 and 48 hours of incubation. RESULTS In the Meise System test series, 12 vials were tested, providing 192 measurements over 12 hours with a 2-hour application interval. With the COL System, 16 vials were tested, resulting in 448 measurements with a 1-hour application interval over 12 hours. Neither the Meise nor the COL System showed contamination of any application after 24 hours of incubation. After 48 hours of incubation, two vials of the Meise System showed a contamination in one measurement, but subsequent applications were sterile again. In the COL System, nine measurements in seven vials were positive. In three of these vials, the last application at 24 hours showed contamination after 48 hours of incubation, where no further drops were applied. CONCLUSION The study confirms the sterility of ASEDs in two reclosable types of ophtiole systems during single-day use in laboratory-simulated conditions within 12 hours of application and 24 hours of incubation time. This is consistent with our several years of clinical experience of the absence of ocular infections caused by the use of ASEDs in the described ophtioles.
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Affiliation(s)
- Frank Blaser
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Isabelle Meneau
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Jürg Wiedler
- Blutspendezentrum Zürich, Schweizerisches Rotes Kreuz, Zurich, Switzerland
| | - Olga Lamprecht
- Blutspendezentrum Zürich, Schweizerisches Rotes Kreuz, Zurich, Switzerland
| | - Daniel Barthelmes
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Sandrine Zweifel
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Philip Perschak
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | | | - Fabienne Fierz
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Sadiq Said
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Anahita Bajka
- Department of Ophthalmology, University Hospital Zurich, Switzerland
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Wu KY, Kearn N, Truong D, Choulakian MY, Tran SD. Advances in Regenerative Medicine, Cell Therapy, and 3D Bioprinting for Corneal, Oculoplastic, and Orbital Surgery. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025. [PMID: 40131704 DOI: 10.1007/5584_2025_855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
Advances in regenerative medicine, cell therapy, and 3D bioprinting are reshaping the landscape of ocular surgery, offering innovative approaches to address complex conditions affecting the cornea, ocular adnexal structures, and the orbit. These technologies hold the potential to enhance treatment precision, improve functional outcomes, and address limitations in traditional surgical and therapeutic interventions.The cornea, as the eye's primary refractive and protective barrier, is particularly well-suited for regenerative approaches due to its avascular and immune-privileged nature. Cell-based therapies, including limbal stem cell transplantation as well as stromal keratocyte and corneal endothelial cell regeneration, are being investigated for their potential to restore corneal clarity and function in conditions such as limbal stem cell deficiency, keratoconus, and endothelial dysfunction. Simultaneously, 3D bioprinting technologies are enabling the development of biomimetic corneal constructs, potentially addressing the global shortage of donor tissues and facilitating personalized surgical solutions.In oculoplastic and orbital surgery, regenerative strategies and cell therapies are emerging as possible alternatives to conventional approaches for conditions such as eyelid defects, meibomian gland dysfunction, and Graves' orbitopathy. Stem cell-based therapies and bioengineered scaffolds are showing potential in restoring lacrimal glands' function as well as reconstructing complex ocular adnexal and orbital structures. Moreover, 3D-printed orbital implants and scaffolds offer innovative solutions for repairing traumatic, post-tumor resection, and congenital defects, with the potential for improved biocompatibility and precision.Molecular and gene-based therapies, including exosome delivery systems, nanoparticle-based interventions, and gene-editing techniques, are expanding the therapeutic arsenal for ophthalmic disorders. These approaches aim to enhance the efficacy of regenerative treatments by addressing underlying pathophysiological mechanisms of diseases. This chapter provides an overview of these advancements and the challenges of translating laboratory discoveries into effective therapies in clinical practice.
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Affiliation(s)
- Kevin Y Wu
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC, Canada
| | - Natalie Kearn
- Department of Medicine, School of Medicine, Queen's University, Kingston, ON, Canada
| | - Doanh Truong
- College of Arts & Science, Case Western Reserve University, Cleveland, OH, USA
| | - Mazen Y Choulakian
- Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC, Canada
| | - Simon D Tran
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada.
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Ziafati M, Mirshahi R, Cicinelli MV, Nazari R. Persistent Corneal Epithelial Defect Following Pars Plana Vitrectomy: A Narrative Review. Semin Ophthalmol 2025:1-13. [PMID: 39989218 DOI: 10.1080/08820538.2025.2470253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 02/12/2025] [Accepted: 02/17/2025] [Indexed: 02/25/2025]
Abstract
PURPOSE Persistent corneal epithelial defects (PCEDs) following pars plana vitrectomy (PPV) represent a significant clinical challenge, potentially leading to corneal scarring, vision loss, and other severe complications. This review aims to summarize the prevalence, associated risk factors, and management strategies for PCEDs in the context of PPV, providing evidence-based guidance for clinicians. METHODS A comprehensive systematic review was conducted using PubMed and Embase databases, identifying English-language studies addressing PCEDs after PPV. RESULTS The prevalence of PCEDs post-PPV varied widely, from 0% to 78.37%, influenced by intrinsic factors such as diabetes mellitus, which impairs corneal nerve function and healing, and extrinsic factors like intraoperative tamponade with C3F8. Management strategies ranged from conservative options like bandage contact lenses to advanced treatments like topical insulin. CONCLUSION PCEDs after PPV are multifactorial and demand individualized management. Advanced therapies, particularly serum-based treatments, and topical insulin, show promising outcomes. Further prospective research is warranted to refine these treatments.
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Affiliation(s)
- Makan Ziafati
- The Five Senses Institute, Rassoul Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Mirshahi
- The Five Senses Institute, Rassoul Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maria Vittoria Cicinelli
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Rezvaneh Nazari
- The Five Senses Institute, Rassoul Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Jongkhajornpong P, Lekhanont K, Rattanasiri S, Pisitkun P, Thakkinstian A. Comparison of Corneal Epitheliotrophic Factors of Undiluted Autologous Platelet-Rich Plasma and Autologous Serum Eye Drops for Dry Eye Disease. Ophthalmol Ther 2025; 14:363-377. [PMID: 39704778 PMCID: PMC11754550 DOI: 10.1007/s40123-024-01082-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 11/28/2024] [Indexed: 12/21/2024] Open
Abstract
INTRODUCTION The purpose of this study was to compare the growth factor concentrations in undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) eye drops. METHODS This was a single-center, prospective trial conducted in a tertiary university hospital in Bangkok, Thailand. Ninety-six patients with moderate-to-severe dry eye disease, who were randomly assigned to receive either 100% APRP or 100% AS, were enrolled in the study. Primary outcome measures were the concentrations of epitheliotrophic factors, including epithelial growth factor (EGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), β-nerve growth factor (β-NGF), platelet-derived growth factor (PDGF)-AA, PDGF-BB, transforming growth factor (TGF)-α, TGF-β1, and vascular endothelial growth factor (VEGF) in 100% APRP and 100% AS. Secondary outcome measures were the correlations between baseline patient characteristics and each growth factor concentration. RESULTS Undiluted APRP contained more EGF, bFGF, and β-NGF than undiluted AS (P < 0.001, P < 0.001, P = 0.018, respectively). Meanwhile, undiluted AS yielded higher concentrations of HGF, PDGF-AA, PDGF-BB, and VEGF compared with undiluted APRP (P < 0.001 all). There were no significant differences in TGF-α and TGF-β1 concentrations between the two groups. In the 100% APRP group, the platelet concentrations had positive correlations with the concentrations of EGF (P = 0.028) and VEGF (P = 0.020). In the 100% AS group, Sjögren's syndrome negatively correlated with the concentrations of PDGF-BB (P = 0.028) and VEGF (P = 0.023). Diabetes mellitus (DM) showed negative correlations with the concentrations of HGF (P = 0.001), TGF-α (P = 0.001), and VEGF (P = 0.002). CONCLUSIONS With our simple preparation protocols, 100% APRP contains higher concentrations of EGF, bFGF, and β-NGF, whereas 100% AS contains higher concentrations of HGF, PDGF-AA, PDGF-BB, and VEGF. This could allow ophthalmologists to tailor treatments to individual patients by targeting growth factor supply based on their underlying pathophysiology. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT04683796.
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Affiliation(s)
- Passara Jongkhajornpong
- Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, Thung Phaya Thai, Ratchathewi, Bangkok, 10400, Thailand
| | - Kaevalin Lekhanont
- Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd, Thung Phaya Thai, Ratchathewi, Bangkok, 10400, Thailand.
| | - Sasivimol Rattanasiri
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Prapaporn Pisitkun
- Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Ammarin Thakkinstian
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Suleman A, Aluyi-Osa G, Ashipa F, Spadea L, Gagliano C, D’Esposito F, Zeppieri M, Musa M. Autologous blood in the management of ocular surface disorders. World J Exp Med 2024; 14:96412. [PMID: 39713083 PMCID: PMC11551708 DOI: 10.5493/wjem.v14.i4.96412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/23/2024] [Accepted: 10/22/2024] [Indexed: 10/31/2024] Open
Abstract
Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders. This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders, encompassing its physiological basis, clinical applications, techniques, challenges, and future perspectives. The ocular surface, comprising the cornea, conjunctiva, and tear film, plays a critical role in maintaining visual function, and its disruption can lead to various pathological conditions. With its rich composition of growth factors, cytokines, and other bioactive molecules, autologous blood offers therapeutic potential in promoting corneal wound healing, reducing inflammation, and improving tear film stability. Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders, including persistent epithelial defects, neurotrophic keratopathy, and dry eye disease. However, challenges such as variability in treatment response, adverse effects, and optimal patient selection remain areas of concern. Further research is needed to elucidate the underlying mechanisms of action, refine treatment protocols, and explore synergistic approaches with other therapeutic modalities. Despite these challenges, autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders, offering new avenues for improving patient outcomes and quality of life. This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders. Current clinical trials are also summarized, and a comparison between autologous blood therapy and conventional eyedrops is attempted. Finally, safe techniques and protocols for autologous blood medicine are elucidated, and adverse effects and future perspectives of this novel therapy are reviewed.
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Affiliation(s)
- Ayuba Suleman
- Department of Ophthalmology, Africa Eye Laser Centre, Km 7, Benin 300105, Nigeria
| | - Gladness Aluyi-Osa
- Department of Ophthalmology, Africa Eye Laser Centre, Km 7, Benin 300105, Nigeria
| | | | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, “Sapienza” University of Rome, Rome 00142, Italy
| | - Caterina Gagliano
- Department of Medicine and Surgery, University of Enna “Kore”, Enna 94100, Italy
- Mediterranean Foundation “G.B. Morgagni”, Catania 95125, Italy
| | - Fabiana D’Esposito
- Imperial College Ophthalmic Research Group Unit, Imperial College, London NW1 5QH, United Kingdom
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| | - Mutali Musa
- Department of Optometry, University of Benin, Benin 3000283, Nigeria
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Jongkhajornpong P, Lekhanont K, Rattanasiri S, Numthavaj P, McKay G, Attia J, Thakkinstian A. Efficacy of 100% autologous platelet-rich plasma and 100% autologous serum in dry eye disease: a randomised controlled trial. BMJ Open Ophthalmol 2024; 9:e001857. [PMID: 39384222 PMCID: PMC11474780 DOI: 10.1136/bmjophth-2024-001857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 09/21/2024] [Indexed: 10/11/2024] Open
Abstract
OBJECTIVE The 0bjective is to compare treatment effects between undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) in patients with moderate-to-severe dry eye disease (DED). METHODS AND ANALYSIS A single-centre, randomised, double-masked, non-inferiority clinical trial was conducted. 96 adult DED patients with an Ocular Surface Disease Index (OSDI) Score of ≥23 and/or Oxford staining grade of ≥2 were randomised to receive either 100% APRP (n=48) or 100% AS (n=48) for 4 weeks. Primary outcomes included OSDI Score and ocular surface staining measured by Oxford grading scale at 4 weeks. Secondary outcomes included fluorescein tear break-up time, Schirmer's test, meibum quality and expressibility, and adverse events. The 95% CI for the mean difference in OSDI scores between groups was estimated to assess non-inferiority of the OSDI score at a prespecified margin of 4.18 points. RESULTS At week 4, there was no significant difference in decreased OSDI scores between groups, with the mean difference (100% APRP-100% AS) of 1.41 (95% CI -1.26, 4.08, p=0.299). The upper limit was less than the prespecified margin, indicating non-inferiority of 100% APRP vs 100% AS. The probabilities of achieving an Oxford grade 0-1 after treatment were not significantly different between groups, with an OR of 0.61 (95% CI 0.25, 1.52, p=0.288). No significant differences in secondary outcomes were observed between groups. CONCLUSION In the short-term, 100% APRP was not inferior to 100% AS in reducing dry eye symptoms and ocular surface staining in moderate-to-severe DED. TRIAL REGISTRATION NUMBER NCT04683796.
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Affiliation(s)
- Passara Jongkhajornpong
- Department of Ophthalmology, Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
| | - Kaevalin Lekhanont
- Department of Ophthalmology, Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
| | - Sasivimol Rattanasiri
- Department of Clinical Epidemiology and Biostatistics, Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
| | - Pawin Numthavaj
- Department of Clinical Epidemiology and Biostatistics, Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
| | | | - John Attia
- Centre for Clinical Ophthalmology and Biostatistics and School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
- Department of Medicine, John Hunter Hospital, University of Newcastle Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Ammarin Thakkinstian
- Department of Clinical Epidemiology and Biostatistics, Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
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Li S, Sun H, Chen L, Fu Y. Targeting limbal epithelial stem cells: master conductors of corneal epithelial regeneration from the bench to multilevel theranostics. J Transl Med 2024; 22:794. [PMID: 39198892 PMCID: PMC11350997 DOI: 10.1186/s12967-024-05603-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 08/10/2024] [Indexed: 09/01/2024] Open
Abstract
The cornea is the outermost layer of the eye and plays an essential role in our visual system. Limbal epithelial stem cells (LESCs), which are localized to a highly regulated limbal niche, are the master conductors of corneal epithelial regeneration. Damage to LESCs and their niche may result in limbal stem cell deficiency (LSCD), a disease confused ophthalmologists so many years and can lead to corneal conjunctivalization, neovascularization, and even blindness. How to restore the LESCs function is the hot topic for ocular scientists and clinicians around the world. This review introduced LESCs and the niche microenvironment, outlined various techniques for isolating and culturing LESCs used in LSCD research, presented common diseases that cause LSCD, and provided a comprehensive overview of both the diagnosis and multiple treatments for LSCD from basic research to clinical therapies, especially the emerging cell therapies based on various stem cell sources. In addition, we also innovatively concluded the latest strategies in recent years, including exogenous drugs, tissue engineering, nanotechnology, exosome and gene therapy, as well as the ongoing clinical trials for treating LSCD in recent five years. Finally, we highlighted challenges from bench to bedside in LSCD and discussed cutting-edge areas in LSCD therapeutic research. We hope that this review could pave the way for future research and translation on treating LSCD, a crucial step in the field of ocular health.
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Affiliation(s)
- Shiding Li
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai, 200011, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, 639 Zhizaoju Rd, Shanghai, 200011, China
| | - Hao Sun
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai, 200011, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, 639 Zhizaoju Rd, Shanghai, 200011, China
| | - Liangbo Chen
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai, 200011, China.
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, 639 Zhizaoju Rd, Shanghai, 200011, China.
| | - Yao Fu
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai, 200011, China.
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, 639 Zhizaoju Rd, Shanghai, 200011, China.
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Anam A, Liu C, Tong L, Liu YC. Blood-Derived Eye Drops for the Treatment of Corneal Neuropathic Pain. J Ocul Pharmacol Ther 2024; 40:281-292. [PMID: 38648544 PMCID: PMC11296151 DOI: 10.1089/jop.2023.0155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 03/18/2024] [Indexed: 04/25/2024] Open
Abstract
Blood-derived preparations, including autologous or allogenic serum, umbilical cord serum/plasma, and platelet-rich plasma eye drops, contain various growth factors, cytokines, and immunoglobulins that resemble natural tears. These components play important roles in corneal cell migration, proliferation, and wound healing. Blood-derived eye drops have demonstrated clinical effectiveness across a spectrum of ocular surface conditions, encompassing dry eye disease, Sjögren's syndrome, graft-versus-host disease, and neuropathic corneal pain (NCP). Currently, management of NCP remains challenging. The emergence of blood-derived eye drops represents a promising therapeutic approach. In this review, we discuss the benefits and limitations of different blood-derived eye drops, their mechanisms of action, and treatment efficacy in patients with NCP. Several studies have demonstrated the clinical efficacy of autologous serum eye drops in relieving pain and pain-like symptoms, such as allodynia and photoallodynia. Corneal nerve parameters were also significantly improved, as evidenced by increased nerve fiber density, length, nerve reflectivity, and tortuosity, as well as a decreased occurrence of beading and neuromas after the treatment. The extent of nerve regeneration correlated with improvement in patient-reported photoallodynia. Cord plasma eye drops also show potential for symptom alleviation and corneal nerve regeneration. Future directions for clinical practice and research involve standardizing preparation protocols, establishing treatment guidelines, elucidating underlying mechanisms, conducting long-term clinical trials, and implementing cost-effective measures such as scaling up manufacturing. With ongoing advancements, blood-derived eye drops hold promise as a valuable therapeutic option for patients suffering from NCP.
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Affiliation(s)
- Ansa Anam
- Department of Ophthalmology, MTI Khyber Teaching Hospital, Peshawar, Pakistan
| | - Chang Liu
- Cornea and Refractive Surgery Group, Singapore Eye Research Institute, Singapore, Singapore
| | - Louis Tong
- Department of Corneal and External Eye Disease, Singapore National Eye Centre, Singapore, Singapore
- Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Ocular Surface Group, Singapore Eye Research Institute, Singapore, Singapore
| | - Yu-Chi Liu
- Cornea and Refractive Surgery Group, Singapore Eye Research Institute, Singapore, Singapore
- Department of Corneal and External Eye Disease, Singapore National Eye Centre, Singapore, Singapore
- Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
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Abdi P, Ghaffari R, Azad N, Alshaheeb A, Latifi G, Soltani Shahgoli S, Fakhredin H. Topical insulin for refractory persistent corneal epithelial defects. Sci Rep 2024; 14:12459. [PMID: 38816428 PMCID: PMC11139959 DOI: 10.1038/s41598-024-63091-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 05/24/2024] [Indexed: 06/01/2024] Open
Abstract
The aim was clinical evaluation of the efficacy of topical insulin eye drops in patients with refractory persistent epithelial defects (PEDs). This prospective non-randomized investigation was conducted to examine the efficacy of insulin eye drops in treating patients with PEDs that did not respond to conventional therapy. A total of twenty-three patients were included in the study, and they were administered insulin eye drops formulated as 1 U/mL, four times a day. The rate of epithelial defect resolution and time to complete corneal re-epithelialization were considered primary outcome measures. The relative prognostic impact of initial wound size and other parameters, including age, sex, smoking, diabetes, and hypertension were also analyzed. The results showed that during follow-up (maximum 50 days), a total of 16 patients (69.6%) achieved improvement. Insulin eye drops significantly reduced the corneal wounding area in 75% of patients with small epithelial defects (5.5 mm2 or less) during 20 days. Only 61% of patients with moderate epithelial defects (5.51-16 mm2) showed a significant recovery in 20-30 days. Also, 71% of patients with a defect size greater than 16 mm2, demonstrated a significant improvement in the rate of corneal epithelial wound healing in about 50 days. In conclusion topical insulin reduces the PED area and accelerates the ocular surface epithelium wound healing.
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Affiliation(s)
- Parisa Abdi
- Translational ophthalmology Research center, Farabi Eye Hospital, School of medicine, Tehran University of Medical Sciences, Tehran, Iran.
- Ophthalmology Department, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Reza Ghaffari
- Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA
| | - Nikoo Azad
- Department of Plant Sciences, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Ahmed Alshaheeb
- Translational ophthalmology Research center, Farabi Eye Hospital, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Golshan Latifi
- Translational ophthalmology Research center, Farabi Eye Hospital, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
- Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA
| | - Sahel Soltani Shahgoli
- Translational ophthalmology Research center, Farabi Eye Hospital, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanieh Fakhredin
- Translational ophthalmology Research center, Farabi Eye Hospital, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
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Vicario-de-la-Torre M, Puebla-García V, Ybañez-García L, López-Cano JJ, González-Cela-Casamayor MA, Brugnera M, Burgos-Blasco B, Díaz-Valle D, Gegúndez-Fernández JA, Benítez-del-Castillo JM, Herrero-Vanrell R. Topical Insulin Eye Drops: Stability and Safety of Two Compounded Formulations for Treating Persistent Corneal Epithelial Defects. Pharmaceutics 2024; 16:580. [PMID: 38794241 PMCID: PMC11124528 DOI: 10.3390/pharmaceutics16050580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/12/2024] [Accepted: 04/19/2024] [Indexed: 05/26/2024] Open
Abstract
Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280-300 mOsm/L), had a pH close to neutral (7-8), medium surface-tension values (<56 MN/m-1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90-110% range in the compounded formulations containing normal saline solution when stored at 2-8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.
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Affiliation(s)
- Marta Vicario-de-la-Torre
- Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain (R.H.-V.)
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
| | | | | | - José Javier López-Cano
- Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain (R.H.-V.)
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
| | - Miriam Ana González-Cela-Casamayor
- Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain (R.H.-V.)
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
| | - Marco Brugnera
- Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain (R.H.-V.)
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
| | - Bárbara Burgos-Blasco
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
- Ocular Surface and Inflammation Unit, Department of Ophthalmology, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain
| | - David Díaz-Valle
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
- Ocular Surface and Inflammation Unit, Department of Ophthalmology, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain
| | - José Antonio Gegúndez-Fernández
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
- Ocular Surface and Inflammation Unit, Department of Ophthalmology, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain
| | - José Manuel Benítez-del-Castillo
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
- Ocular Surface and Inflammation Unit, Department of Ophthalmology, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain
| | - Rocío Herrero-Vanrell
- Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy (UCM), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain (R.H.-V.)
- National Ocular Pathology Network (OFTARED), Carlos III Institute of Health, San Carlos Clinical Hospital Institute of Health Research (IdISSC), 28040 Madrid, Spain (D.D.-V.)
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11
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Blaser F, Meneau I, Mihic-Probst D, Muth DR, Barthelmes D, Zweifel S, Said S, Bajka A. A Novel Technique of Aseptic Manufacture of Autologous Serum Eye Drops (ASEDs) and Sterility Analysis of the Bottled Ophtioles. Klin Monbl Augenheilkd 2024; 241:392-397. [PMID: 38653293 DOI: 10.1055/a-2249-0056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
PURPOSE To introduce a novel technique of the aseptic manufacture of autologous serum eye drops (ASEDs) with a prefiltered closed system and to analyze the sterility of the produced ophtioles between 2018 and 2022. METHODS This is a prospective single-center study conducted at the Department of Ophthalmology at a Swiss University Hospital between 2018 and 2022. For regulatory reasons, closed systems for manufacturing ASEDs are strongly recommended. We attached an upstream sterile filter (Sterivex PES0.22 µm Burlington, USA) to a commercially available closed system (COL System Modena, Italy) for manufacturing ASEDs. The goal of this novel approach was to reduce the microbiological contamination of the donated autologous blood. Using the presented manufacturing method, we are able to produce, on average, 56 ophtioles per batch, containing either 1.45 mL or 2.5 mL of autologous serum per ophtiole. For each batch of ASEDs, we performed a microbiological analysis by automated blood culture testing (BACTEC). This system examines the presence of bacteria and fungi. RESULTS We analyzed all manufactured batches between 2018 and 2022. None of the 2297 batches and the resulting 129 060 ophtioles showed bacterial or mycotic contamination. During the analyzed period, two batches were discarded: one due to fibrin-lipid aggregations, further microbiological and histological work-up excluded any contamination; another due to false-positive HIV in serological testing. Overall, the contamination rate was 0%, and the batch discharge rate was 0.09%. CONCLUSIONS The combination of upstream sterile filtration with a commercial closed system for manufacturing ASEDs proved to be effective in ensuring sterility without any contamination over the past 4 years. This is becoming crucial, as the demand for autologous blood products for treating ocular surface disorders, such as refractory dry eyes or nonhealing defects of the corneal epithelium, is on the rise.
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Affiliation(s)
- Frank Blaser
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
| | - Isabelle Meneau
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
| | - Daniela Mihic-Probst
- Department of Pathology and Molecular Pathology, UniversitätsSpital Zürich, Switzerland
| | - Daniel Rudolf Muth
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
- Department of Clinical Neuro Science, Karolinska Institutet, Stockholm, Sweden
| | - Daniel Barthelmes
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
- Save Sight Institute, University of Sydney CAR, Glebe, Australia
| | - Sandrine Zweifel
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
| | - Sadiq Said
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
| | - Anahita Bajka
- Department of Ophthalmology, UniversitätsSpital Zürich, Switzerland
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12
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Kwaku Akowuah P, Junior Obinwanne C, Owusu E, Kyeremeh S, Bonsu K, Karikari LAA, Akyaa Akomeah F, Kyei Nkansah E, Kobia-Acquah E. Platelet-rich plasma for treating dry eye disease - A systematic review and meta-analysis. Cont Lens Anterior Eye 2024; 47:102091. [PMID: 37951738 DOI: 10.1016/j.clae.2023.102091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 10/20/2023] [Accepted: 11/04/2023] [Indexed: 11/14/2023]
Abstract
PURPOSE Dry eye disease has public health and economic significance. Platelet-rich plasma is rich in anti-inflammatory agents and growth factors, both beneficial for ocular surface repair. This study aimed to conduct a systematic review and meta-analysis to summarize the benefits of platelet-rich plasma for treating dry eye disease and its adverse effects. METHODS Prospective comparative studies using platelet-rich plasma as monotherapy for dry eye disease were included for efficacy assessment. Before-after studies were included for adverse events assessment. Data sources included PubMed, Google Scholar, Web of Science, and Scopus. A systematic review and meta-analysis protocol was pre-registered on PROSPERO (CRD42022347982). PRISMA guidelines were followed. The National Health Institute (NIH) quality assessment tool for before-after studies, the Cochrane risk of bias tool (RoB2), and the methodological index for non-randomized studies were used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. RESULTS 19 studies (10 comparative and 9 before-after) were included in the systematic review and meta-analysis. The occurrence rate of adverse effects was 2.6 % (95 % CI: 0.5 - 4.7). The pooled standardized mean difference (SMD) for dry eye symptoms was 0.81 (95 % CI: 0.25 - 1.37; I2 = 82 %; p < 0.00001; Z = 2.84, p = 0.004); tear quality was 0.44 (95 % CI: 0.06 - 0.81; I2 = 67 %; p = 0.003; Z = 2.26, p = 0.02); tear quantity was 0.45 (95 % CI: 0.03 - 0.88; I2 = 74 %; p = 0.0003; Z = 2.10, p = 0.04); and corneal staining 0.72 (95 % CI: 0.14 - 1.30; I2 = 85 %; p < 0.00001; Z = 2.43, p = 0.02). CONCLUSION The current study shows that platelet-rich plasma is efficacious in managing dry eye disease, significantly reducing dry eye signs and symptoms. Such significant improvements could translate to improved quality of life.
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Affiliation(s)
| | | | - Ebenezer Owusu
- College of Optometry, University of Houston, Houston, TX, USA.
| | - Sylvester Kyeremeh
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Kwaku Bonsu
- College of Optometry, University of Houston, Houston, TX, USA.
| | | | - Felicia Akyaa Akomeah
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Ernest Kyei Nkansah
- Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland
| | - Emmanuel Kobia-Acquah
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland.
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13
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Shome S, Kodieswaran M, Dadheech R, Chevella M, Sensharma S, Awasthi S, Bandyopadhyay A, Mandal BB. Recent advances in platelet-rich plasma and its derivatives: therapeutic agents for tissue engineering and regenerative medicine. PROGRESS IN BIOMEDICAL ENGINEERING (BRISTOL, ENGLAND) 2024; 6:012004. [PMID: 39655847 DOI: 10.1088/2516-1091/ad1338] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/07/2023] [Indexed: 12/18/2024]
Abstract
Platelet rich plasma (PRP) is a suspension of bioactive factors and chemokine enriched plasma. Platelets are a distinctive source of membrane bound and soluble proteins that are released upon their activation. The higher count of platelets renders PRP with an array of tissue regenerative abilities. PRP can be employed in the form of platelet containing plasma, platelet lysate plasma, or in the form of a pre-gelled fibrin matrix. PRP has been an essential alternative source of growth factors in the healing and regeneration of various tissues, such as musculoskeletal, cardiovascular, and dermal tissue, with additional applications in other tissues, such as hepatic and neural. A wide range of preparative and isolation strategies have been developed for various forms of PRP at laboratory and commercial scales. Concomitantly, PRP has found its applicability as an active component in several tissue regenerative approaches, including 3D printed/bioprinted constructs, injectable hydrogels, and crosslinked scaffolds. This review focuses on the various forms of PRP and their preparation methods, the latest tissue engineering applications of PRP, and the various tissue-specific clinical trials and findings conducted using PRP. We have further discussed the optimizations required in the methods of preparation, delivery, and long-term storage of PRP. Therefore, this review seeks to benefit the scope of research on PRP-based therapeutic agents in tissue engineering by providing comprehensive insights into the widespread application. We envisage PRP could be instrumental in future patient-specific tissue engineering applications in both pre-clinical and clinical settings.
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Affiliation(s)
- Sayanti Shome
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - M Kodieswaran
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Rajat Dadheech
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Maheshwari Chevella
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Sreemoyee Sensharma
- Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Sanu Awasthi
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Ashutosh Bandyopadhyay
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Biman B Mandal
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
- Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
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14
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Okumura Y, Inomata T, Fujimoto K, Fujio K, Zhu J, Yanagawa A, Shokirova H, Saita Y, Kobayashi Y, Nagao M, Nishio H, Sung J, Midorikawa-Inomata A, Eguchi A, Nagino K, Akasaki Y, Hirosawa K, Huang T, Kuwahara M, Murakami A. Biological effects of stored platelet-rich plasma eye-drops in corneal wound healing. Br J Ophthalmol 2023; 108:37-44. [PMID: 36162968 DOI: 10.1136/bjo-2022-322068] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 09/08/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND/AIMS This study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops. METHODS At our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-β1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours. RESULTS Higher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-β1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops. CONCLUSION PRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders.
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Affiliation(s)
- Yuichi Okumura
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Takenori Inomata
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Hospital Administration, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- AI Incubation Farm, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Keiichi Fujimoto
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Kenta Fujio
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Jun Zhu
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Ai Yanagawa
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Hurramhon Shokirova
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Yoshitomo Saita
- Department of Sports and Regenerative Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopedics, Juntendo University Faculty of Medicine, Bunkyo-ku, Japan
| | - Yohei Kobayashi
- Department of Sports and Regenerative Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopedics, Juntendo University Faculty of Medicine, Bunkyo-ku, Japan
| | - Masahi Nagao
- Department of Sports and Regenerative Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopedics, Juntendo University Faculty of Medicine, Bunkyo-ku, Japan
- Department of Medical Technology Innovation Center, Juntendo University, Bunkyo-ku, Japan
| | - Hirofumi Nishio
- Department of Sports and Regenerative Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Orthopedics, Juntendo University Faculty of Medicine, Bunkyo-ku, Japan
| | - Jaemyoung Sung
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- University of South Florida College of Medicine, Tampa, Florida, USA
| | - Akie Midorikawa-Inomata
- Department of Hospital Administration, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Atsuko Eguchi
- Department of Hospital Administration, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Ken Nagino
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Hospital Administration, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Yasutsugu Akasaki
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Kunihiko Hirosawa
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Tianxiang Huang
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Mizu Kuwahara
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
| | - Akira Murakami
- Department of Ophthalmology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
- Department of Digital Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
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15
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Kang MJ, Lee JH, Hwang J, Chung SH. Efficacy and safety of platelet-rich plasma and autologous-serum eye drops for dry eye in primary Sjögren's syndrome: a randomized trial. Sci Rep 2023; 13:19279. [PMID: 37935760 PMCID: PMC10630514 DOI: 10.1038/s41598-023-46671-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 11/03/2023] [Indexed: 11/09/2023] Open
Abstract
We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren's syndrome (SS). This prospective, randomized, double-blinded clinical study included patients diagnosed with primary SS DE. Thirty-eight participants were randomly assigned to the AS or PRP groups. Corneal and conjunctival staining scores, Schirmer I test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at 4 and 12 weeks. Conjunctival impression cytology (CIC) metaplasia grade and goblet cell density grade at 12 weeks were compared with those at baseline. Corneal and conjunctival staining scores and TBUT significantly improved at 4 and 12 weeks in both groups (all p < 0.005). No significant difference between the AS and PRP groups was observed at 4 and 12 weeks. The Schirmer I values, OSDI scores, CIC metaplasia grade, and goblet cell density grade did not significantly change at 4 and 12 weeks in either group. Both AS and PRP eye drops are effective for primary SS DE without a significant difference. Considering that the preparation time of PRP is shorter than that of AS, PRP can be a good alternative treatment for primary SS DE.
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Affiliation(s)
- Min-Ji Kang
- Department of Ophthalmology, College of Medicine, Sanggye Paik Hospital, Inje University, Seoul, Republic of Korea
| | - Jee Hye Lee
- Department of Ophthalmology, College of Medicine, Sanggye Paik Hospital, Inje University, Seoul, Republic of Korea
| | - Jehyung Hwang
- Department of Ophthalmology, College of Medicine, Sanggye Paik Hospital, Inje University, Seoul, Republic of Korea
| | - So-Hyang Chung
- Department of Ophthalmology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, #222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
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16
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Thia ZZ, Ho YT, Shih KC, Tong L. New developments in the management of persistent corneal epithelial defects. Surv Ophthalmol 2023; 68:1093-1114. [PMID: 37301520 DOI: 10.1016/j.survophthal.2023.06.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 05/24/2023] [Accepted: 06/05/2023] [Indexed: 06/12/2023]
Abstract
A persistent epithelial defect (PED) is a corneal epithelial defect that failed to heal after 2weeks. It is a condition that carries much morbidity, and our understanding of PED remains poor, with current treatment methods often having unsatisfactory outcomes. With PEDs becoming more prevalent, more efforts are required to establish reliable treatment modalities. Our reviews describe the causes of PEDs and the different approaches developed to manage them, as well as their associated limitations. Emphasis is placed on understanding various advances in the development of new treatment modalities. We have also described a case of a woman with a background of graft-versus-host disease on long-term topical corticosteroids who developed complicated PED involving both eyes. The current approach to managing PEDs generally involves exclusion of an active infection, followed by treatment modalities that aim to encourage corneal epithelial healing. Success rates, however, remain far from desirable, as treatment remains challenging due to multiple underlying etiologies. In summary, advances in the development of new therapies may be able to facilitate progress in the understanding and treatment of PED.
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Affiliation(s)
- Zhang Zhe Thia
- Singapore Eye Research Institute, Singapore, Singapore; National University Hospital, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yik To Ho
- Hong Kong University, Pok Fu Lam, Hong Kong
| | | | - Louis Tong
- Singapore Eye Research Institute, Singapore, Singapore; Singapore National Eye Center, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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17
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Sharun K, Chandran D, Manjusha KM, Mankuzhy PD, Kumar R, Pawde AM, Dhama K, El-Husseiny HM, Amarpal. Advances and prospects of platelet-rich plasma therapy in veterinary ophthalmology. Vet Res Commun 2023; 47:1031-1045. [PMID: 36607500 DOI: 10.1007/s11259-022-10064-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 12/28/2022] [Indexed: 01/07/2023]
Abstract
In the recent decades, there has been a significant uptick on the use of platelet-rich plasma (PRP) as a better alternative for ophthalmologic therapies in pathologies, primarily of the ocular surface. PRP is a class of liquid platelet concentrate containing a supra-physiological concentration of platelets in a relatively small amount of plasma. Its potential to heal various tissues has piqued interest in its therapeutic application as a biomaterial in regenerative medicine. It is currently a popular therapeutic agent in plastic surgery, cardiothoracic surgery, reconstructive surgery, and even oral and maxillofacial surgery. Based on the data from in vitro and in vivo studies, it can be concluded that PRP possesses adequate therapeutic potential in ocular pathologies, especially those involving cornea. In addition, the high concentrations of growth factors (TGF-β, VEGF, EGF) present in the PRP accelerate the healing of the corneal epithelium. PRP has great therapeutic prospects in veterinary ophthalmology as a regenerative therapeutic modality. However, several variables are yet to be defined and standardized that can directly affect the efficacy of PRP application in different ophthalmic conditions. There is a shortage of research on the use of PRP in ocular surface defects compared to the number of studies and reports on the use of autologous and allogeneic serum eye drops. Therefore, a data-driven approach is required to generate consensus/guidelines for the preparation, characterization, and therapeutic use of PRP in veterinary ophthalmology. This review aims to inform readers of the latest research on PRP, including its preparation methods, physiological and biochemical properties, clinical applications in veterinary ophthalmology, and their safety and efficacy.
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Affiliation(s)
- Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India.
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore, Tamil Nadu, 642109, India
| | - K M Manjusha
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India
| | - Pratheesh D Mankuzhy
- Department of Physiology, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, India
| | - Rohit Kumar
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India
| | - Abhijit M Pawde
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India
| | - Hussein M El-Husseiny
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology (TUAT), Fuchu, Tokyo, 183-0054, Japan
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, 13736, Toukh, Egypt
| | - Amarpal
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India
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18
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Liu Y, Ding S, Sun JF, Li PP, Li XQ, Zeng LY, Xu KL, Qiao JL. [The effect of platelet infusion on the repair of bone marrow hematopoietic niche damage in mice induced by (60)Co radiation and hematopoietic reconstruction after bone marrow transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2023; 44:635-641. [PMID: 37803836 PMCID: PMC10520226 DOI: 10.3760/cma.j.issn.0253-2727.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Indexed: 10/08/2023]
Abstract
Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.
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Affiliation(s)
- Y Liu
- Department of Clinical Laboratory, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China
| | - S Ding
- Department of Clinical Laboratory, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China
| | - J F Sun
- Department of Clinical Laboratory, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China
| | - P P Li
- Department of Clinical Laboratory, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China
| | - X Q Li
- Blood Disease Institute, Xuzhou Medical University, Key Laboratory of Bone Marrow Stem Cell, Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China
| | - L Y Zeng
- Blood Disease Institute, Xuzhou Medical University, Key Laboratory of Bone Marrow Stem Cell, Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China
| | - K L Xu
- Blood Disease Institute, Xuzhou Medical University, Key Laboratory of Bone Marrow Stem Cell, Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China
| | - J L Qiao
- Blood Disease Institute, Xuzhou Medical University, Key Laboratory of Bone Marrow Stem Cell, Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China
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Balal S, Din N, Ashton C, Ahmad S. Healing of Chemical Injury-Related Persistent Corneal Epithelial Defects With Topical Insulin. Cornea 2023; 42:1000-1004. [PMID: 36729695 DOI: 10.1097/ico.0000000000003145] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/01/2022] [Indexed: 02/03/2023]
Abstract
PURPOSE The purpose of this study was to evaluate the effectiveness of insulin eye drops for treating refractory persistent epithelial defects (PEDs). METHODS A prospective, single-center, case series was performed from March 2020 to September 2021. All patients were prescribed insulin eye drops for refractory PEDs that failed on maximum standard medical treatment (including serum eye drops). The drops were used 4 times/day. Patients were followed up at 2 weekly intervals with full slitlamp examination and serial anterior segment photography. The primary end point was resolution of the epithelial defect. RESULTS Eleven eyes of 10 patients were treated with insulin eye drops. The mean age of the cohort was 45.4 + 25 years with a mean follow-up of 195.7 + 114.3 days after re-epithelization. The most common causative condition was chemical injury (n = 5, 60%). Mean baseline PED defect was 41.3 + 55.2 mm 2 . Nine of 11 eyes (82%) fully re-epithelized within a mean time of 62.3 + 34.6 days (range 14-112). In 2 patients who did not achieve re-epithelization, one had a reduction in size from 12.25 mm 2 to 4.5 mm 2 and the other had no response. No recurrence in defect was observed in the group that had fully re-epithelized. CONCLUSIONS This study showed that the use of topical insulin eye drops led to a successful resolution of PED in 9 of 11 cases. We demonstrate the use of insulin for closure of PEDs in chemical eye injury. Larger controlled studies are required to further evaluate this novel therapy.
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Affiliation(s)
- Shafi Balal
- Moorfields Eye Hospital, London, United Kingdom; and
- UCL Institute of Ophthalmology, London, United Kingdom
| | - Nizar Din
- Moorfields Eye Hospital, London, United Kingdom; and
| | | | - Sajjad Ahmad
- Moorfields Eye Hospital, London, United Kingdom; and
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20
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Ghalibafan S, Osei K, Amescua G, Sabater A. Efficacy of Plasma Rich in Growth Factors (PRGF) in Stage 1 Neurotrophic Keratitis. RESEARCH SQUARE 2023:rs.3.rs-3040369. [PMID: 37461454 PMCID: PMC10350222 DOI: 10.21203/rs.3.rs-3040369/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/24/2023]
Abstract
Background/Aims Neurotrophic keratitis (NK) is a neurodegenerative disease that can lead to corneal hypoesthesia, decreased tear production, and epitheliopathy. Based on the severity of ocular surface damage, NK is classified into 3 stages. Stage 1 NK is characterized by superficial punctate keratopathy, tear film instability, and reduced corneal sensation. The therapeutic efficacy of PRGF eye drops for NK stages 2 and 3 has been previously reported. In this study, we evaluated the efficacy and safety of autologous PRGF eye drops in improving corneal sensitivity and other ocular surface clinical signs in patients with stage 1 NK. Methods Retrospective chart review. Results 26 eyes of 15 stage 1 NK patients (seven males, eight females), aged 76.3 ± 12.1 years, were included in the study. The mean treatment duration was 2 ± 1.8 months. With PRGF treatment, corneal sensitivity increased from 2.8 to 4.5 cm in 53.8% (14/26) (p < 0.01), TBUT increased from 3.6 to 5.0 s in 69.2% (18/26) (p < 0.01), and Schirmer score increased from 13.7 to 16.8 mm in 80.7% (21/26) of treated eyes (p < 0.01). Similarly, an improvement in corneal staining (punctate epithelial erosions) and MMP-9 levels was seen in 80.7% (n = 21) and 65.4% (n = 17) of treated eyes, respectively. BCVA improvement was seen in 26.9% of treated eyes (n = 7). Conclusions This study demonstrates the effective role of PRGF therapy in recovering corneal sensation and tear film function and in the healing of corneal erosions in stage 1 NK patients.
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Affiliation(s)
| | - Kwaku Osei
- University of Miami Miller School of Medicine
| | - Guillermo Amescua
- Bascom Palmer Eye institute, University of Miami, Miller School of Medicine
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21
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Wróbel-Dudzińska D, Przekora A, Kazimierczak P, Ćwiklińska-Haszcz A, Kosior-Jarecka E, Żarnowski T. The Comparison between the Composition of 100% Autologous Serum and 100% Platelet-Rich Plasma Eye Drops and Their Impact on the Treatment Effectiveness of Dry Eye Disease in Primary Sjogren Syndrome. J Clin Med 2023; 12:jcm12093126. [PMID: 37176566 PMCID: PMC10179661 DOI: 10.3390/jcm12093126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 04/22/2023] [Accepted: 04/23/2023] [Indexed: 05/15/2023] Open
Abstract
PURPOSE The aim of the study was to compare the difference in composition between 100% autologous serum (AS) and 100% platelet-rich plasma (PRP) eye drops and assess their impact on the clinical outcomes after the treatment of severe dry eye (DE) in primary Sjogren Syndrome patients (pSS). MATERIALS AND METHODS This is an interventional, non-randomized, comparative, three-month study. 22 patients with severe DE in pSS were treated with 100% AS (22 eyes) and 100% PRP (22 eyes) eye drops 5 times per day in monotherapy mode. The quantifications of growth factors (GFs) such as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), transforming growth factor (TGF-b), insulin-like growth factor (IGF), fibronectin, and substance p in hemoderivates were done. The main outcome measures were: Ocular Surface Disease Index (OSDI), Best Corrected Visual Acuity (BCVA), the Schirmer test, tear break-up time (TBUT), corneal and conjunctival staining according to the Oxford scale, conjunctival hyperaemia, and Meibomian gland parameters. The results were compared at baseline, 1 month, and 3 months following the treatment. The clinical results were correlated with the concentration of GFs in the biological tear substitutes. RESULTS Significant differences were observed in the concentration of FGF (4.42 ± 0.86 vs. 15.96 ± 7.63, p < 0.0001), EGF (4.98 ± 0.97 vs. 39.06 ± 20.18, p < 0.0001), fibronectin (929.6 ± 111.5 vs. 823.64 ± 98.49, p = 0.0005), VEGF (175.45 ± 65.93 vs. 717.35 ± 488.15, p < 0.0001), PDGF AB (619.6 ± 117.30 vs. 349.66 ± 79.82, p < 0.0001), NGF (85.22 ± 23.49 vs. 8.29 ± 9.06, p < 0.0001), PDGF (935.38 ± 434.26 vs. 126.66 ± 54.41, p < 0.0001), substance p (112.58 ± 27.28 vs. 127.51 ± 26.56, p = 0.0125) in PRP compared to AS. The level of TGF-β was undoubtedly higher in AS than in PRP (1031.37 ± 330.23 vs. 726.03 ± 298.95, p = 0.0004). No significant differences between AS and PRP were observed in the concentration of IGF. Therapy with blood products relieved the signs and symptoms in pSS DE patients. There was a statistically significant improvement in BCVA, the Schirmer test, TBUT, Meibomian gland parameters, and the reduction of the OSDI scores, Oxford staining, and conjunctiva hyperaemia in each of the groups. However, the clinical changes were more significant in the PRP group. There were numerous correlations between the level of GFs and the mean change in clinical outcomes. No adverse events were reported. CONCLUSIONS Despite the fact that blood derivatives differ in composition, they seem to be effective and safe in the treatment of severe DE in pSS patients. The signs and symptoms of DE were reduced in both groups, but only the mean change in OSDI was statistically significant. A greater reduction in OSDI scores was observed in the PRP group. The obtained results and the composition of haemoderivates may indicate the superiority of PRP in relieving the symptoms of DE in pSS patients compared to AS.
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Affiliation(s)
- Dominika Wróbel-Dudzińska
- Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, 20-059 Lublin, Poland
| | - Agata Przekora
- Independent Unit of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, 20-059 Lublin, Poland
| | - Paulina Kazimierczak
- Independent Unit of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, 20-059 Lublin, Poland
| | | | - Ewa Kosior-Jarecka
- Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, 20-059 Lublin, Poland
| | - Tomasz Żarnowski
- Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, 20-059 Lublin, Poland
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22
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Allogeneic Solid Platelet-Rich Plasma for Persistent Epithelial Neurotrophic Defects: A Protocol and Pilot Study. Cornea 2023; 42:498-506. [PMID: 36729664 DOI: 10.1097/ico.0000000000003204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 10/27/2022] [Indexed: 02/03/2023]
Abstract
PURPOSE Here, we present the procedure to obtain allogeneic solid platelet-rich plasma (PRP) and its use in a pilot study of patients with persistent neurotrophic epithelial defects. METHODS We included 4 eyes of 4 patients with persistent neurotrophic epithelial defects unresponsive to other therapies from a single institution. PRP and thrombin were produced by the Department of Transfusion Medicine from healthy blood donors. PRP was activated in its solid form in the operating room with addition of thrombin and calcium gluconate 10% and applied on the cornea with fibrin glue and soft contact lens. Corneal healing time, corneal esthesiometry, visual acuity, Oxford staining score, Ocular Surface Disease Index questionnaire, and Schirmer I test were recorded. Anterior segment optical coherence tomography and in vivo confocal microscopy were also evaluated over the 4-month follow-up period. RESULTS The persistent epithelial defect healed in all patients in the first 10 days. During the follow-up, there was an absence of recurrences. For all patients, there was a reduction in Ocular Surface Disease Index questionnaire score (case 1: -55 points, -73.3%; case 2: -26.3 points, -58.4%; case 3: -56 points, -69.1%; case 4: -20 points, -26.6%; mean reduction: 39.3 points, 56.85%) and Oxford staining score (case 1, 2, and 3: 3 points decrease; case 4: 2 points decrease; mean reduction: -2.75 points). CONCLUSIONS Allogeneic solid PRP in combination with fibrin glue may facilitate wound healing in neurotrophic persistent epithelial defects. Further prospective studies are needed to quantify its efficacy.
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Troha K, Vozel D, Arko M, Bedina Zavec A, Dolinar D, Hočevar M, Jan Z, Kisovec M, Kocjančič B, Pađen L, Pajnič M, Penič S, Romolo A, Repar N, Spasovski V, Steiner N, Šuštar V, Iglič A, Drobne D, Kogej K, Battelino S, Kralj-Iglič V. Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review. Int J Mol Sci 2023; 24:3420. [PMID: 36834843 PMCID: PMC9959846 DOI: 10.3390/ijms24043420] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/24/2023] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
The preparation of autologous platelet and extracellular vesicle-rich plasma (PVRP) has been explored in many medical fields with the aim to benefit from its healing potential. In parallel, efforts are being invested to understand the function and dynamics of PVRP that is complex in its composition and interactions. Some clinical evidence reveals beneficial effects of PVRP, while some report that there were no effects. To optimize the preparation methods, functions and mechanisms of PVRP, its constituents should be better understood. With the intention to promote further studies of autologous therapeutic PVRP, we performed a review on some topics regarding PVRP composition, harvesting, assessment and preservation, and also on clinical experience following PVRP application in humans and animals. Besides the acknowledged actions of platelets, leukocytes and different molecules, we focus on extracellular vesicles that were found abundant in PVRP.
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Affiliation(s)
- Kaja Troha
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Domen Vozel
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Faculty of Medicine, SI-1000 Ljubljana, Slovenia
| | - Matevž Arko
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Apolonija Bedina Zavec
- Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, SI-1000 Ljubjana, Slovenia
| | - Drago Dolinar
- Department of Orthopedic Surgery, University Medical Centre, Zaloška 9, SI-1000 Ljubljana, Slovenia
- MD-RI Institute for Materials Research in Medicine, Bohoričeva 5, SI-1000 Ljubljana, Slovenia
| | - Matej Hočevar
- Department of Physics and Chemistry of Materials, Institute of Metals and Technology, SI-1000 Ljubljana, Slovenia
| | - Zala Jan
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Matic Kisovec
- Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, SI-1000 Ljubjana, Slovenia
| | - Boštjan Kocjančič
- Department of Orthopedic Surgery, University Medical Centre, Zaloška 9, SI-1000 Ljubljana, Slovenia
| | - Ljubiša Pađen
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Manca Pajnič
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Samo Penič
- University of Ljubljana, Laboratory of Physics, Faculty of Electrical Engineering, SI-1000 Ljubljana, Slovenia
| | - Anna Romolo
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Laboratory of Physics, Faculty of Electrical Engineering, SI-1000 Ljubljana, Slovenia
| | - Neža Repar
- University of Ljubljana, Research Group for Nanobiology and Nanotoxicology, Biotechnical Faculty, SI-1000 Ljubljana, Slovenia
| | - Vesna Spasovski
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
- Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia
| | - Nejc Steiner
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Vid Šuštar
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Aleš Iglič
- University of Ljubljana, Laboratory of Physics, Faculty of Electrical Engineering, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Medicine, SI-1000 Ljubljana, Slovenia
| | - Damjana Drobne
- University of Ljubljana, Research Group for Nanobiology and Nanotoxicology, Biotechnical Faculty, SI-1000 Ljubljana, Slovenia
| | - Ksenija Kogej
- University of Ljubljana, Chair of Physical Chemistry, Faculty of Chemistry and Chemical Technology, SI-1000 Ljubljana, Slovenia
| | - Saba Battelino
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Faculty of Medicine, SI-1000 Ljubljana, Slovenia
| | - Veronika Kralj-Iglič
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
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Akbari E, Imani R, Shokrollahi P, Jarchizadeh R, Heidari keshel S. Hydrogel-based formulations for drug delivery to the anterior segment of the eye. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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25
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Soleimani M, Cheraqpour K, Koganti R, Baharnoori SM, Djalilian AR. Concise Review: Bioengineering of Limbal Stem Cell Niche. Bioengineering (Basel) 2023; 10:111. [PMID: 36671683 PMCID: PMC9855097 DOI: 10.3390/bioengineering10010111] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/01/2023] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
The corneal epithelium is composed of nonkeratinized stratified squamous cells and has a significant turnover rate. Limbal integrity is vital to maintain the clarity and avascularity of the cornea as well as regeneration of the corneal epithelium. Limbal epithelial stem cells (LESCs) are located in the basal epithelial layer of the limbus and preserve this homeostasis. Proper functioning of LESCs is dependent on a specific microenvironment, known as the limbal stem cell niche (LSCN). This structure is made up of various cells, an extracellular matrix (ECM), and signaling molecules. Different etiologies may damage the LSCN, leading to limbal stem cell deficiency (LSCD), which is characterized by conjunctivalization of the cornea. In this review, we first summarize the basics of the LSCN and then focus on current and emerging bioengineering strategies for LSCN restoration to combat LSCD.
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Affiliation(s)
- Mohammad Soleimani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 1336616351, Iran
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Kasra Cheraqpour
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran 1336616351, Iran
| | - Raghuram Koganti
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Seyed Mahbod Baharnoori
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Ali R. Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
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Mini-Conjunctival Limbal Autograft (Mini-CLAU) Using Platelet-Rich Plasma Eye Drops (E-PRP): A Case Series. Cornea 2022:00003226-990000000-00145. [PMID: 36730781 DOI: 10.1097/ico.0000000000003156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 08/14/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE The purpose of this study was to introduce a new method of limbal stem cell transplantation using autologous platelet-rich plasma (E-PRP) eye drops for unilateral total limbal stem cell deficiency. METHODS Patients with total unilateral limbal stem cell deficiency due to chemical burn underwent mini-conjunctival limbal autograft using autologous E-PRP drops. One small limbal block, measuring 2 × 2 mm, was harvested from the patients' contralateral healthy eye and transplanted to the diseased eye. All patients received E-PRP drops until achieving complete corneal epithelialization. Subsequent corneal transplantation was performed in eyes with significant stromal opacification. Corneal buttons obtained during corneal transplantation underwent immunohistochemistry for the evaluation of limbal stem cell markers (ABCG2 and P63). Visual acuity, epithelial healing, corneal clarity, and regression of corneal conjunctivalization/vascularization were evaluated after surgery. RESULTS Ten patients with acid (n = 7) or alkali (n = 3) burn were included. The mean follow-up period was 21.7 ± 5.8 months (range, 12-32 months). Corneas were completely reepithelialized within 14.9 ± 3.5 days (range, 11-21 days). Corneal conjunctivalization/vascularization dramatically regressed 1 to 2 months after surgery in all cases, and corneal clarity considerably improved in 7 patients. In the 3 eyes with significant stromal opacification, subsequent optical penetrating keratoplasty was performed. The ocular surface was stable throughout the follow-up period in all eyes. BSCVA improved to 0.60 ± 0.0.32 and 0.46 ± 0.0.25 logMAR in eyes with and without corneal transplantation, respectively, at the final follow-up visit. ABCG2 and P63 markers were detected on corneal buttons after keratoplasty. CONCLUSIONS Based on our clinical and laboratory findings, mini-conjunctival limbal autograft using E-PRP can be considered as a promising alternative to ocular surface reconstruction.
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Jongkhajornpong P, Anothaisintawee T, Lekhanont K, Numthavaj P, McKay G, Attia J, Thakkinstian A. Short-term Efficacy and Safety of Biological Tear Substitutes and Topical Secretagogues for Dry Eye Disease: A Systematic Review and Network Meta-analysis. Cornea 2022; 41:1137-1149. [PMID: 34924549 PMCID: PMC9365259 DOI: 10.1097/ico.0000000000002943] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE The purpose of this study was to assess short-term efficacy and safety of tear promotion eye drops (biological tear substitutes and topical secretagogues) for treating dry eye disease. METHODS Randomized controlled trials comparing short-term effects of biological tear substitutes or topical secretagogues versus placebo or other topical dry eye treatments in adults with dry eye disease were identified from the MEDLINE, Embase, Scopus, ClinicalTrials.gov , and World Health Organization International Clinical Trials Registry Platform databases. Pairwise meta-analysis and network meta-analysis were performed. Outcomes were ocular symptoms, ocular surface staining, tear break-up time, Schirmer test, and adverse events. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS Thirty-nine randomized controlled trials (3693 patients) were eligible. Using artificial tears as a reference, autologous platelet lysate was the most effective treatment for lowering ocular surface disease index (unstandardized mean difference [USMD] -31.85; 95% confidence interval [CI]: -43.19 to -20.51) and platelet rich plasma showed the most reduction in corneal fluorescein staining scores (standardized mean difference -2.52; 95% CI: -3.23 to -1.82). Cord blood serum was the most effective treatment for increasing tear break-up time (USMD 2.67; 95% CI: 0.53-4.82), and eledoisin was superior to others in improving Schirmer scores (USMD 2.28; 95% CI: 0.14-4.42). Most interventions did not significantly increase ocular adverse events compared with artificial tears. CONCLUSIONS Biological tear substitutes, including autologous serum, autologous platelet lysate, platelet rich plasma, and cord blood serum, might be the most effective treatment among tear promotion eye drops in relieving dry eye symptoms without increasing adverse events. However, there remains uncertainty around these findings because of low/very low certainty of evidence.
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Affiliation(s)
- Passara Jongkhajornpong
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Thunyarat Anothaisintawee
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Department of Family Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Kaevalin Lekhanont
- Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pawin Numthavaj
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Gareth McKay
- Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland; and
| | - John Attia
- School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia
| | - Ammarin Thakkinstian
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Diaz‐Valle D, Burgos‐Blasco B, Rego‐Lorca D, Puebla‐Garcia V, Perez‐Garcia P, Benitez‐del‐Castillo JM, Herrero‐Vanrell R, Vicario‐de‐la‐Torre M, Gegundez‐Fernandez JA. Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea. Acta Ophthalmol 2022; 100:e912-e919. [PMID: 34407296 DOI: 10.1111/aos.14997] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/21/2021] [Accepted: 08/04/2021] [Indexed: 01/01/2023]
Abstract
PURPOSE To investigate the effect of topical insulin on epithelization in persistent epithelial defects (PED) refractory to usual treatment compared to autologous serum. DESIGN Retrospective, consecutive case-control series. METHODS The charts of 61 consecutive patients with PED treated with topical insulin (case group) and 23 treated with autologous serum (control group) were reviewed. Primary efficacy end points were the percentage of patients in which epithelization was achieved, as well as the rate and time until epithelization. Secondary efficacy point was need for amniotic membrane transplantation (AMT) or other surgeries. RESULTS Mean time between PED diagnosis and start of topical insulin was 22.7 ± 18.5 days (range 13-115) and the mean area was 14.8 ± 16.2 mm2 (range 1.1-70.6). In the control group, mean time was 27.9 ± 16.8 days, mean epithelial defect area being 18.6 ± 15.0 mm2 (range 1.7-52.9). No differences in baseline characteristics were found between groups (p > 0.05). Epithelization was achieved in 51 patients (84%) on insulin and 11 patients (48%) on autologous serum (p = 0.002). In those patients, mean time until reepithelization was 32.6 ± 28.3 days (range 4-124) in the insulin group and 82.6 ± 82.4 days (range 13-231) in the autologous serum group (p = 0.011). The need for AMT was significantly lower in the insulin group (p = 0.005). PED recurrence was higher in patients treated on autologous serum (43%) compared with insulin (11%) (p = 0.002). CONCLUSIONS Topical insulin is an effective treatment and safely promotes healing of PED. In our series, topical insulin presented better epithelization outcomes than autologous serum and could thus be considered as a first-line treatment.
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Affiliation(s)
- David Diaz‐Valle
- Servicio de Oftalmología Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) Hospital Clinico San Carlos Madrid Spain
| | - Barbara Burgos‐Blasco
- Servicio de Oftalmología Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) Hospital Clinico San Carlos Madrid Spain
| | - Daniela Rego‐Lorca
- Servicio de Oftalmología Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) Hospital Clinico San Carlos Madrid Spain
| | | | - Pilar Perez‐Garcia
- Servicio de Oftalmología Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) Hospital Clinico San Carlos Madrid Spain
| | - Jose M. Benitez‐del‐Castillo
- Servicio de Oftalmología Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) Hospital Clinico San Carlos Madrid Spain
| | - Rocio Herrero‐Vanrell
- Departamento de Farmacia y Tecnología Farmacéutica Facultad de Farmacia Universidad Complutense de Madrid Madrid España
| | - Marta Vicario‐de‐la‐Torre
- Departamento de Farmacia y Tecnología Farmacéutica Facultad de Farmacia Universidad Complutense de Madrid Madrid España
| | - Jose A. Gegundez‐Fernandez
- Servicio de Oftalmología Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) Hospital Clinico San Carlos Madrid Spain
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Comparison of epitheliotrophic factors in platelet-rich plasma versus autologous serum and their treatment efficacy in dry eye disease. Sci Rep 2022; 12:8906. [PMID: 35618742 PMCID: PMC9135723 DOI: 10.1038/s41598-022-12879-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/16/2022] [Indexed: 11/25/2022] Open
Abstract
Current treatment of severe dry eye disease (DED) includes blood-derived eye drops, such as autologous serum (AS), which lubricate the eyes and provide factors that improve ocular surface and aid in wound healing. Recent studies indicated that platelet-rich plasma (PRP) was also effective. This study aims to compare the concentration and stability of epitheliotrophic factors in AS and PRP and their efficacy in DED patients. Epitheliotrophic factors of interest are epidermal growth factor (EGF), fibronectin, platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-beta1 (TGF-β1). We determined that all epitheliotrophic factors were present in AS and PRP at baseline and did not decrease in concentrations in all storage conditions (4 °C for 1 week and at − 20 °C for 1 and 3 months). However, differences in concentrations in AS and PRP were observed. PRP was also shown not to be inferior to AS in terms of efficacy in DED treatment in a prospective randomized control trial which evaluated ocular surface disease index, dry eye questionnaire, ocular surface staining, tear breakup time, and Schirmer test at baseline and at 1-month follow-up. Therefore, with its shorter preparation time, PRP could be considered as an alternative to AS for the treatment of DED.
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Koay SY, Larkin DFP. New Pharmacological Approaches for the Treatment of Neurotrophic Keratitis. Front Pharmacol 2022; 13:796854. [PMID: 35392574 PMCID: PMC8981034 DOI: 10.3389/fphar.2022.796854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 03/07/2022] [Indexed: 11/24/2022] Open
Abstract
Neurotrophic keratitis (NK) is a rare degenerative condition that is caused by damage to the trigeminal nerve, with partial or complete loss of corneal sensory innervation. The loss of innervation leads to impaired healing of corneal epithelium, which subsequently results in punctate epithelial erosions, persistent epithelial defects, corneal ulcers and corneal perforation. Management of NK is often supportive and aims to promote epithelial healing and prevent progression of disease. Multiple novel pharmacological approaches have been proposed to address the underlying pathophysiology of NK, which are discussed in this paper.
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Affiliation(s)
- Su Yin Koay
- Cornea and External Diseases Service, Moorfields Eye Hospital, London, United Kingdom
| | - Daniel F P Larkin
- Cornea and External Diseases Service, Moorfields Eye Hospital, London, United Kingdom
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Elhusseiny AM, Soleimani M, Eleiwa TK, ElSheikh RH, Frank CR, Naderan M, Yazdanpanah G, Rosenblatt MI, Djalilian AR. OUP accepted manuscript. Stem Cells Transl Med 2022; 11:259-268. [PMID: 35303110 PMCID: PMC8968724 DOI: 10.1093/stcltm/szab028] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/06/2021] [Indexed: 11/24/2022] Open
Abstract
The corneal epithelium serves to protect the underlying cornea from the external environment and is essential for corneal transparency and optimal visual function. Regeneration of this epithelium is dependent on a population of stem cells residing in the basal layer of the limbus, the junction between the cornea and the sclera. The limbus provides the limbal epithelial stem cells (LESCs) with an optimal microenvironment, the limbal niche, which strictly regulates their proliferation and differentiation. Disturbances to the LESCs and/or their niche can lead to the pathologic condition known as limbal stem cell deficiency (LSCD) whereby the corneal epithelium is not generated effectively. This has deleterious effects on the corneal and visual function, due to impaired healing and secondary corneal opacification. In this concise review, we summarize the characteristics of LESCs and their niche, and present the current and future perspectives in the management of LSCD with an emphasis on restoring the function of the limbal niche.
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Affiliation(s)
- Abdelrahman M Elhusseiny
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
- Department of Ophthalmology, Harvey and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Mohammad Soleimani
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Taher K Eleiwa
- Department of Ophthalmology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Reem H ElSheikh
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Charles R Frank
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Morteza Naderan
- Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghasem Yazdanpanah
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Mark I Rosenblatt
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Ali R Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
- Corresponding author: Ali R. Djalilian, Cornea Service, Stem Cell Therapy and Corneal Tissue Engineering Laboratory, Illinois Eye and Ear Infirmary, 1855 W. Taylor Street, M/C 648, Chicago, IL 60612, USA.
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Effect of Platelet-Rich Plasma on Corneal Epithelial Healing after Phototherapeutic Keratectomy: An Intraindividual Contralateral Randomized Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5752248. [PMID: 34873572 PMCID: PMC8643227 DOI: 10.1155/2021/5752248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 09/09/2021] [Accepted: 11/16/2021] [Indexed: 12/04/2022]
Abstract
Purpose To assess the effect of platelet-rich plasma (PRP) on the healing response of the corneal epithelium in eyes undergoing phototherapeutic keratectomy (PTK). Methods We prospectively examined 20 eyes of 10 patients undergoing bilateral PTK for granular corneal dystrophy or band keratopathy. Patients were randomly assigned to start topical administration of PRP ophthalmic suspension (PRP group) or artificial tears (control group) 4 times daily for 2 weeks. Immediately, 1, and 2 days, and 1 week after PTK, we quantitatively measured the staining area of the corneal epithelium, using slit-lamp photography. We also determined the subjective symptoms and the satisfaction, using the visual analogue system (VAS). Results The staining area in the PRP group was significantly smaller than that in the control group on days 1 and 2 (Wilcoxon signed-rank test, p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). The recovery rate of the corneal epithelium in the PRP group was significantly higher than that in the control group on days 1 and 2 (p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). We found no significant differences in pain (p = 0.139), foreign body sensation (p = 0.108), epiphora (p = 1.000), or satisfaction (p = 0.295), between the two groups. Postoperative complications did not occur in any of the eyes in the study. Conclusions The PRP treatment was effective for enhancing corneal epithelial recovery in the early postoperative period, without significant adverse events, in post-PTK-treated eyes, suggesting that it may hold promise as one of the treatment options for treating such postsurgical patients.
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Fitriana PO, Pawiroranu S, Widayanti TW, Wirohadidjojo YW, Mahayana IT. Autologous platelet-rich plasma eye drop for moderate-to-severe bacterial corneal ulcers: Changes in interleukin-6 tear concentration and clinical outcomes. Taiwan J Ophthalmol 2021; 12:457-461. [PMID: 36660115 PMCID: PMC9843573 DOI: 10.4103/tjo.tjo_42_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 09/30/2021] [Indexed: 01/22/2023] Open
Abstract
PURPOSE The objective of this study was to evaluate interleukin-6 (IL-6) tear concentration and clinical outcome in patients with moderate-to-severe bacterial corneal ulcers post autologous platelet-rich plasma (PRP) eye drop therapy. MATERIALS AND METHODS This was a pre-post designed study involving 21 moderate-severe corneal ulcer patients who got autologous PRP eye drop. Subjects were got autologous PRP eye drop as adjuvant therapy. Patients with moderate-to-severe infectious bacterial corneal ulcers were included in this study. Tear sampling was performed before therapy using sterile Schirmer paper from conjunctival inferior fornix. PRP therapy was performed for 7 days. Data recording and tear sampling were then performed at day 0 (pre-PRP), day 7 (D+7), and day 14 (D+14) after PRP therapy. Data recording included presence of pericorneal injection, blepharospasm, size of corneal defects, and hypopyon. RESULTS There was a decrease in IL-6 tear concentration by day 14 after PRP therapy (P < 0.001). IL-6 concentration at day 7 after therapy (7525.67 ± 7092 pg/mL) tended to be lower before therapy (10,599 ± 6158 pg/mL), but not statistically significant (P = 0.156). The size of corneal defects decreased significantly post PRP at day 7 (P = 0.035) and at day 14 (P = 0.001). There was a significant blepharospasm at day 7 (P = 0.012) and day 14 (P < 0.001). There was a significant pericorneal injection only at day 14 (P = 0.002). There was no significant decreased hypopyon. CONCLUSION There was a significant reduction in IL-6 tear concentration and clinical improvement in moderate-to-severe bacterial corneal ulcers which got autologous PRP eye drop as adjuvant therapy.
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Affiliation(s)
- Prili Olda Fitriana
- Department of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Suhardjo Pawiroranu
- Department of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Tri Wahyu Widayanti
- Department of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Yohanes Widodo Wirohadidjojo
- Department of Dermato and Venereology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | - Indra Tri Mahayana
- Department of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia,Address for correspondence: Dr. Indra Tri Mahayana, Department of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Jl. Farmako, Sekip Utara, Yogyakarta, 55284, Indonesia. E-mail: ;
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Peláez P, Damiá E, Torres-Torrillas M, Chicharro D, Cuervo B, Miguel L, del Romero A, Carrillo JM, Sopena JJ, Rubio M. Cell and Cell Free Therapies in Osteoarthritis. Biomedicines 2021; 9:1726. [PMID: 34829953 PMCID: PMC8615373 DOI: 10.3390/biomedicines9111726] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/12/2021] [Accepted: 11/16/2021] [Indexed: 12/18/2022] Open
Abstract
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients' function, decreasing quality of life. There are many limitations regarding OA conventional therapies-pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies' efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.
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Affiliation(s)
- Pau Peláez
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Elena Damiá
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Marta Torres-Torrillas
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Deborah Chicharro
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Belén Cuervo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Laura Miguel
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Ayla del Romero
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Jose Maria Carrillo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Joaquín J. Sopena
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Mónica Rubio
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
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Amin S, Jalilian E, Katz E, Frank C, Yazdanpanah G, Guaiquil VH, Rosenblatt MI, Djalilian AR. The Limbal Niche and Regenerative Strategies. Vision (Basel) 2021; 5:vision5040043. [PMID: 34698278 PMCID: PMC8544688 DOI: 10.3390/vision5040043] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/27/2021] [Accepted: 09/16/2021] [Indexed: 12/17/2022] Open
Abstract
The protective function and transparency provided by the corneal epithelium are dependent on and maintained by the regenerative capacity of limbal epithelial stem cells (LESCs). These LESCs are supported by the limbal niche, a specialized microenvironment consisting of cellular and non-cellular components. Disruption of the limbal niche, primarily from injuries or inflammatory processes, can negatively impact the regenerative ability of LESCs. Limbal stem cell deficiency (LSCD) directly hampers the regenerative ability of the corneal epithelium and allows the conjunctival epithelium to invade the cornea, which results in severe visual impairment. Treatment involves restoring the LESC population and functionality; however, few clinically practiced therapies currently exist. This review outlines the current understanding of the limbal niche, its pathology and the emerging approaches targeted at restoring the limbal niche. Most emerging approaches are in developmental phases but show promise for treating LSCD and accelerating corneal regeneration. Specifically, we examine cell-based therapies, bio-active extracellular matrices and soluble factor therapies in considerable depth.
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Affiliation(s)
- Sohil Amin
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
| | - Elmira Jalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
| | - Eitan Katz
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
| | - Charlie Frank
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
| | - Ghasem Yazdanpanah
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
- Richard and Loan Hill Department of Bioengineering, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Victor H. Guaiquil
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
| | - Mark I. Rosenblatt
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
| | - Ali R. Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA; (S.A.); (E.J.); (E.K.); (C.F.); (G.Y.); (V.H.G.); (M.I.R.)
- Correspondence:
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Pérez ML, Barreales S, Sabater-Cruz N, Martinez-Conesa EM, Vilarrodona A, Casaroli-Marano RP. Amniotic membrane extract eye drops: a new approach to severe ocular surface pathologies. Cell Tissue Bank 2021; 23:473-481. [PMID: 34549352 DOI: 10.1007/s10561-021-09962-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 09/13/2021] [Indexed: 10/20/2022]
Abstract
A protocol for processing amniotic membrane as an extract to be re-hydrated and administered topically as eye drops (amniotic membrane extract eye drops, AMEED) has been developed. Safety and efficacy of AMEED was assessed in patients with severe ocular surface pathologies. prospective clinical follow-up of ocular surface symptoms before and after regular application of the AMEED for at least 4 weeks on patients with severe ocular surface disorders as chronic dry eye disease, limbal stem cell deficiency, neurotrophic ulcer and permanent and disabling symptomatology that were refractory to conventional treatment. Efficacy and tolerability were assessed based on patient-reported symptoms, objective measurements, and reports of adverse events. Thirty-six eyes from 25 patients were included. Although the visual quality function score, by means of a VQF25 questionnaire, was not statistically different after the treatment (p = 0.4657), there was a clear trend, statistically significant, towards the improvement in ocular symptoms like foreign body sensation, itching and stinging (p < 0.05) and clinical presentation of the pathology. All patients with corneal ulcer showed complete epithelization. Topically applied AMEED proved to be safe, well tolerated and effective in reducing the symptoms and clinical signs of severe ocular disease. Further studies are needed to confirm the best indications for AMEED use.
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Affiliation(s)
- Maria Luisa Pérez
- Barcelona Tissue Bank- Banc de Sang i Teixits (BTB), Barcelona, Spain. .,Institute of Biomedical Research (IIB-Sant Pau; SGR1113), Barcelona, Spain.
| | - Saúl Barreales
- Barcelona Tissue Bank- Banc de Sang i Teixits (BTB), Barcelona, Spain
| | - Noelia Sabater-Cruz
- Institut Clinic d'Oftalmologia (ICOF), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Eva Maria Martinez-Conesa
- Barcelona Tissue Bank- Banc de Sang i Teixits (BTB), Barcelona, Spain.,Institute of Biomedical Research (IIB-Sant Pau; SGR1113), Barcelona, Spain
| | - Anna Vilarrodona
- Barcelona Tissue Bank- Banc de Sang i Teixits (BTB), Barcelona, Spain.,Institute of Biomedical Research (IIB-Sant Pau; SGR1113), Barcelona, Spain
| | - Ricardo P Casaroli-Marano
- Barcelona Tissue Bank- Banc de Sang i Teixits (BTB), Barcelona, Spain.,Department of Surgery, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
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Abstract
PURPOSE OF REVIEW Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED. RECENT FINDINGS Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types. SUMMARY Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.
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Affiliation(s)
- Rhiya Mittal
- Ophthalmology, Miami Veterans Affairs Medical Center, Miami, FL, USA
- Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA
| | - Sneh Patel
- Ophthalmology, Miami Veterans Affairs Medical Center, Miami, FL, USA
- Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA
| | - Anat Galor
- Ophthalmology, Miami Veterans Affairs Medical Center, Miami, FL, USA
- Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA
- Research Services, Miami Veterans Affairs Medical Center, Miami, FL, USA
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Farghali HA, AbdElKader NA, AbuBakr HO, Ramadan ES, Khattab MS, Salem NY, Emam IA. Corneal Ulcer in Dogs and Cats: Novel Clinical Application of Regenerative Therapy Using Subconjunctival Injection of Autologous Platelet-Rich Plasma. Front Vet Sci 2021; 8:641265. [PMID: 33816586 PMCID: PMC8012907 DOI: 10.3389/fvets.2021.641265] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/28/2021] [Indexed: 02/03/2023] Open
Abstract
Background: Corneal ulcer could be a major source of distress in small animals, with many contributing agents. In recent years, few studies evaluated the efficacy of platelet-rich plasma (PRP) in healing corneal ulcers. Aim: This study aimed to assess the ability of subconjunctival injection of autologous PRP in the treatment of corneal ulcers in dogs and cats as well as estimate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and oxidative stress biomarkers in these patients. Methods: A total number of 28 animals (16 cats and 12 dogs) were enrolled in this study. Each animal was subjected to clinical, neurologic, and ophthalmic examinations where the type of ulcer was documented. Tear samples were collected for evaluation of oxidative biomarkers and MMPs; conjunctival swabs were taken to identify the involved organism. PRP was prepared from each animal and given as subconjunctival injection; numbers of injections were done according to case response. Clinical follow-up was done and documented for each case. Results: In cat patients, female and Persian cats were most affected; unilateral and superficial ulcers were most recorded. In male dogs, unilateral, and superficial ulcers were most recorded. FHV-1 was most identified in cats, while Staphylococcus aureus was most identified in dogs. Numbers of injections needed to achieve healing were recorded, with 50% of dogs needing two injections with 1-week intervals and 50% of cats needed three injections with 1-week intervals. Alterations in both oxidative biomarkers and MMPs were recorded in affected animals. Conclusion: The use of autologous PRP as a subconjunctival injection in treating corneal ulcers in dogs and cats is effective. The number of injections is the case and corneal ulcer type-dependent. Clinical Significance: Autologous PRP as a subconjunctival injection in treating corneal ulcer is a relatively cheap, safe method and can be done in the clinical setting.
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Affiliation(s)
- Haithem A Farghali
- Department of Surgery, Anaesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Naglaa A AbdElKader
- Department of Surgery, Anaesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Huda O AbuBakr
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Eman S Ramadan
- Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Marwa S Khattab
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Noha Y Salem
- Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Ibrahim A Emam
- Department of Surgery, Anaesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
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Abstract
PURPOSE Autologous hemoderivative eye drops have a role in the management of persistent epithelial defects (PEDs), but their use may be limited by cost and availability. Finger-prick autologous blood (FAB) treatment uses whole capillary blood, obtained from a sterilized fingertip, as an alternative form of hemoderivative eye drop therapy. To date, 1 report has described the safe and effective use of FAB for dry eye and PEDs. We report the results of 10 eyes (10 patients) treated with FAB for PEDs. METHODS Ten patients with PEDs in 1 eye for a mean of 259 ± 201 days due to diabetic neurotrophic keratopathy (n = 3), herpetic keratitis (n = 3), postpenetrating keratoplasty (n = 1), keratoconjunctivitis sicca (n = 1), postradiotherapy (n = 1), and neuropathic ulcer (n = 1) were treated with FAB 4 times a day for 28 days in addition to conventional therapies. All patients had been unsuccessfully treated with conventional therapy before commencing on FAB. None of the patients had received any surgical treatment for PED. RESULTS At day 28, the PED had healed in 60% (n = 6) of the eyes. In 1 eye, the PED reduced in size by half. Thirty percent (n = 3) of patients had incomplete follow-up data at the end of the study. CONCLUSIONS FAB in combination with conventional treatment may be successfully used in the management of refractory PEDs. No adverse effects arising from FAB treatment were observed.
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Panda BB, Mohapatra S, Parida S. Update on the role of Eye platelet-rich plasma (E-PRP) in the treatment of ocular surface disorders. INDIAN JOURNAL OF CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 2020; 6:487-496. [DOI: 10.18231/j.ijceo.2020.106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2024]
Abstract
Platelet rich plasma is the highly concentrated form of autologous human platelets in a small amount of plasma which contains important growth factors and plasma proteins that plays a significant role in wound healing process by epithelial differentiation and collagen bundle organization. In this article, we aim to provide an update on the current literature regarding the eye platelet rich plasma, its methods of preparation, physiological and biochemical properties, its clinical applications, safety and efficacy as compared to other blood derived products etc. In ophthalmology, this product is being used in the management of symptomatic dry eyes, corneal ulcers, periocular chemical and thermal burns, Idiopathic macular hole, Skin rejuvenation post Blepharoplasties and more recently actinic elastosis in the lower eyelid regions. The role of eye platelet rich plasma in ocular surface disorders has been sparsely studied in literature with more studies and reports on the application of autologous and allogeneic serum eye drops and therefore, it becomes very important to update ourselves with more studies in this topic to prove the efficiency of this blood derived product. Moreover, the role of other platelet derived products like platelet rich growth factors, platelet lysate in ocular surface disorders have also been discussed.
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41
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Nosrati H, Abpeikar Z, Mahmoudian ZG, Zafari M, Majidi J, Alizadeh A, Moradi L, Asadpour S. Corneal epithelium tissue engineering: recent advances in regeneration and replacement of corneal surface. Regen Med 2020; 15:2029-2044. [PMID: 33169642 DOI: 10.2217/rme-2019-0055] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Currently, many corneal diseases are treated by corneal transplantation, artificial corneal implantation or, in severe cases, keratoprosthesis. Owing to the shortage of cornea donors and the risks involved with artificial corneal implants, such as infection transmission, researchers continually seek new approaches for corneal regeneration. Corneal tissue engineering is a promising approach that has attracted much attention from researchers and is focused on regenerative strategies using various biomaterials in combination with different cell types. These constructs should have the ability to mimic the native tissue microenvironment and present suitable optical, mechanical and biological properties. In this article, we review studies that have focused on the current clinical techniques for corneal replacement. We also describe tissue-engineering and cell-based approaches for corneal regeneration.
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Affiliation(s)
- Hamed Nosrati
- Department of Tissue Engineering & Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Zahra Abpeikar
- Department of Tissue Engineering & Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Zahra Gholami Mahmoudian
- Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mahdi Zafari
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Jafar Majidi
- Cellular & Molecular Research Center, Basic Health Science Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Akram Alizadeh
- Department of Tissue Engineering & Applied Cell Sciences, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Lida Moradi
- The Ronald O Perelman Department of Dermatology, New York University, School of Medicine, New York, NY 10016, USA.,Department of Cell Biology, New York University, School of Medicine, New York, NY, 10016 USA
| | - Shiva Asadpour
- Department of Tissue Engineering & Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.,Cellular & Molecular Research Center, Basic Health Science Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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42
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Trufanov SV, Subbot AM, Shakhbazyan NP. [Modern biotechnological treatment methods of persistent corneal epithelial defects]. Vestn Oftalmol 2020; 136:277-282. [PMID: 33063977 DOI: 10.17116/oftalma2020136052277] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The article reviews modern methods of treatment of persistent corneal epithelial defects and considers the factors involved in the development of this pathology, including the limbal stem cell deficiency, which is likely to play the main role. The most promising treatment methods are described, particularly the use of blood derivatives and cell therapy.
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Affiliation(s)
- S V Trufanov
- Research Institute of Eye Diseases, Moscow, Russia
| | - A M Subbot
- Research Institute of Eye Diseases, Moscow, Russia
| | - N P Shakhbazyan
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
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43
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You J, Hodge C, Hoque M, Petsoglou C, Sutton G. Human Platelets and Derived Products in Treating Ocular Surface Diseases - A Systematic Review. Clin Ophthalmol 2020; 14:3195-3210. [PMID: 33116370 PMCID: PMC7567560 DOI: 10.2147/opth.s265701] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/26/2020] [Indexed: 12/26/2022] Open
Abstract
Human platelet products have emerged as an alternative treatment for a range of ocular surface diseases such as dry eye and corneal ulceration. With significant therapeutic potential and increasing popularity, this study aimed to conduct a systematic review to detail the various production methods involved in generating platelet-derived products, compare and analyze clinical findings across available studies, and disseminate the relative advantages, limitations, and challenges of using platelet products to treat ocular surface disease. Thirty-eight clinical studies were identified, excluding studies conducted in animals and non-English language. Studies reported clinical outcomes, which included ocular surface disease index, best-corrected visual acuity, and corneal fluorescein staining. Most clinical studies reported improved patient signs and symptoms with an increasing variety of human platelet products including platelet rich plasma eye drops, human platelet lysate and platelet gels. However, due to variations in production methods, and study designs as well as confusing terminology, it was suggested that characterization of platelet products is needed for proper evaluation across studies.
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Affiliation(s)
- Jingjing You
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia
| | - Chris Hodge
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Vision Eye Institute, Chatswood, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia.,Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia
| | | | - Constantinos Petsoglou
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia
| | - Gerard Sutton
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Vision Eye Institute, Chatswood, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia
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44
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Priyadarsini S, Whelchel A, Nicholas S, Sharif R, Riaz K, Karamichos D. Diabetic keratopathy: Insights and challenges. Surv Ophthalmol 2020; 65:513-529. [PMID: 32092364 PMCID: PMC8116932 DOI: 10.1016/j.survophthal.2020.02.005] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 02/10/2020] [Accepted: 02/11/2020] [Indexed: 12/11/2022]
Abstract
Ocular complications from diabetes mellitus are common. Diabetic keratopathy, the most frequent clinical condition affecting the human cornea, is a potentially sight-threatening condition caused mostly by epithelial disturbances that are of clinical and research attention because of their severity. Diabetic keratopathy exhibits several clinical manifestations, including persistent corneal epithelial erosion, superficial punctate keratopathy, delayed epithelial regeneration, and decreased corneal sensitivity, that may lead to compromised visual acuity or permanent vision loss. The limited amount of clinical studies makes it difficult to fully understand the pathobiology of diabetic keratopathy. Effective therapeutic approaches are elusive. We summarize the clinical manifestations of diabetic keratopathy and discuss available treatments and up-to-date research studies in an attempt to provide a thorough overview of the disorder.
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Affiliation(s)
- S Priyadarsini
- Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - A Whelchel
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - S Nicholas
- Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - R Sharif
- Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - K Riaz
- Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - D Karamichos
- Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
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45
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A humoral solution: Autologous blood products and tissue repair. Cell Immunol 2020; 356:104178. [PMID: 32861105 DOI: 10.1016/j.cellimm.2020.104178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 07/12/2020] [Accepted: 07/13/2020] [Indexed: 12/30/2022]
Abstract
Autologous blood-derived products (ABP) are the focus of growing scientific interest and are investigated and used for multiple medical indications. ABPs hold promise thanks to their availability, ease of preparation, and low risk of adverse allogenic reaction, hypersensitivity, and contamination. Compositional analysis of ABPs reveals a diverse mixture of cellular components, cytokines and growth factors that play roles in healing processes such as tissue proliferation and angiogenesis, modulation of the local environment through chemotaxis and regulation of inflammation and the extracellular matrix, as well as several immunomodulatory actions. Thus, the administration of ABP induces supraphysiological levels of components necessary for orchestrating reparative efforts in currently difficult-to-treat medical conditions. In this article, we review the variety of autologous blood-derived products, their composition, current clinical uses, regulatory climate, and mechanisms of action.
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46
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Rodriguez AE, Gisbert S, Palazón A, Alio JL. Quantification of Growth Factors and Fibronectin in Diverse Preparations of Platelet-Rich Plasma for the Treatment of Ocular Surface Disorders (E-PRP). Transl Vis Sci Technol 2020; 9:22. [PMID: 32821519 PMCID: PMC7409215 DOI: 10.1167/tvst.9.6.22] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 03/26/2020] [Indexed: 01/11/2023] Open
Abstract
Purpose The purpose of this study was to quantify the presence of growth factors (GFs) and fibronectin in autologous platelet-rich plasma for topical ocular use (E-PRP) comparing their concentration when different preparation and preservation procedures were applied. Methods E-PRP was prepared with blood from healthy volunteers. The count of platelets, leukocytes, and red blood cells in the whole blood and E-PRP were performed. The concentration of the GFs platelet-derived growth factor BB (PDGF-BB), transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF), vascular endothelial growth factor A (VEGF-A), and fibronectin was determined in each of the four procedures applied including fresh, frozen at −20°C for 3 months, fresh-spin, and frozen-spin at −20°C E-PRP samples. Posterior statistical analysis was performed to establish significant differences between groups and between GFs in relation to the amounts of platelets. Results Platelets in the E-PRP doubled in the number of basal values of whole blood (P ≤ 0.01). The blood cells in the E-PRP decreased drastically in red cells (99%) and also in leukocytes (82%). The concentration of PDGF-BB and EGF was significantly higher (P < 0.01) when the E-PRP samples were frozen at −20°C. However, no significant differences were observed for TGF-β1, VEGF-A, and fibronectin (P > 0.05). The concentration of GFs in the E-PRP did not necessarily correlate with the number of platelets. Conclusions Freezing the E-PRP for 3 months at −20°C increased the concentration of important proteins, such as PDGF-BB and EGF, and maintained the levels of others. These findings are essential because treatments, such as E-PRP, used by patients with ocular surface dysfunctions tend to prolong it in time. In addition, subsequent centrifugation of the E-PRP decreased the values of TFG-β1, but not the other GFs, which would allow adjusting the concentration of TFG-β1, as necessary. This procedure guarantees their correct conservation and viability. Translational Relevance This work demonstrates how clinical application can be improved by starting from basic research. The quantification of GFs and fibronectin in platelet-rich plasma (PRP) helps to clarify which is the best mode of preparation and preservation of PRP for clinical applications. This allows to optimize the product that is delivered to the patients as a treatment for the dysfunctions of the ocular surface, guaranteeing that the conservation does not affect at all the quality of the PRP that it is going to be used.
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Affiliation(s)
- Alejandra E Rodriguez
- Research and Development Laboratory, Vissum Miranza, Alicante, Spain.,Department of Cornea and Refractive Surgery, Vissum Miranza, Alicante, Spain.,Department of Ophthalmology, Miguel Hernandez University, Alicante, Spain
| | - Sandra Gisbert
- Research and Development Laboratory, Vissum Miranza, Alicante, Spain
| | - Antonio Palazón
- Department of Clinical Medicine, Miguel Hernandez University, Alicante, Spain
| | - Jorge L Alio
- Department of Cornea and Refractive Surgery, Vissum Miranza, Alicante, Spain.,Department of Ophthalmology, Miguel Hernandez University, Alicante, Spain
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47
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Autologous platelet-rich plasma in the treatment of refractory corneal ulcers: A case report. Am J Ophthalmol Case Rep 2020; 20:100838. [PMID: 32913920 PMCID: PMC7472805 DOI: 10.1016/j.ajoc.2020.100838] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Revised: 06/25/2020] [Accepted: 07/15/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose To evaluate the efficacy of a low-cost preparation of platelet-rich plasma (PRP) eye drops in the treatment of persistent non-infectious corneal ulcer. Observations A 67-year-old female presented to our clinic with a wide corneal ulcer and severe paracentral corneal thinning refractory to medical therapy with antibiotics, lubricant and contact lens bandage. The patient received a novel preparation of PRP solution. After 15 days of therapy, we observed complete resolution of the corneal ulcer with regrowth of the epithelium and a reduction in corneal opacity. Conclusion and importance Although the low-cost PRP preparation gives a lower platelet concentration than standard procedures, our work shows this preparation to be effective in the treatment of refractory non-infectious corneal ulcer.
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48
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Egrilmez S, Yildirim-Theveny Ş. Treatment-Resistant Bacterial Keratitis: Challenges and Solutions. Clin Ophthalmol 2020; 14:287-297. [PMID: 32099313 PMCID: PMC6996220 DOI: 10.2147/opth.s181997] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 12/10/2019] [Indexed: 12/18/2022] Open
Abstract
Bacterial keratitis is an important ophthalmic emergency and one of the most common causes of corneal blindness. The main causes of treatment resistance in bacterial keratitis are failure to eliminate predisposing factors, misdiagnosis and mistreatment. At first, exogenous, local and systemic predisposing factors that disturbing ocular surface must be eliminated to improve corneal ulcers and to prevent recurrences. Smears and scrapings for staining and culture are indispensable diagnostic tools for cases of sight-threatening keratitis (centrally located, multifocal, characterized by melting, painful). Main treatment agents in bacterial keratitis treatment are topical antibiotics. Until the results of culture antibiograms reach the ophthalmologist, empirical antibiotic selections based on direct microscopic examination and gram stain findings are the most appropriate initial treatment approach currently. S. aureus and coagulase-negative staphylococci (CoNS), the most common gram-positive agents, have resistance rates of more than 30% for fluoroquinolone and methicillin. Multidrug resistance rates are similarly high in these microorganisms. P. aeruginosa is the most common gram-negative micro-organism, in case of multidrug-resistant isolates, both functional and anatomical prognosis of the eyes are very poor. In cases of sight-threatening and resistant keratitis, antibiotic susceptibility testing containing imipenem, colistin, and linezolid is seeming to be an important requirement. Despite its efficiency limited to superficial cases, a nonpharmaceutical anti-infective treatment option such as corneal crosslinking for bacterial keratitis is an emerging hope, while antibiotic resistance increases. ![]()
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/wQSeNbG9dtI
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49
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Ibares-Frías L, Gallego-Muñoz P, Orive G, Anitua E, Cantalapiedra-Rodríguez R, Merayo-Lloves J, Martínez-García M. Potential Effect of Plasma Rich in Growth Factors-Endoret in Stromal Wound Healing in Additive Surgery. Ophthalmic Res 2019; 63:203-212. [DOI: 10.1159/000501507] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 06/17/2019] [Indexed: 11/19/2022]
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50
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Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology. Ophthalmology 2019; 127:128-133. [PMID: 31561880 DOI: 10.1016/j.ophtha.2019.08.018] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 08/16/2019] [Accepted: 08/16/2019] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To describe the safety and effectiveness of using autologous serum-based eye drops for the treatment of severe dry eye and persistent corneal epithelial defect. METHODS Literature searches of the PubMed and Cochrane Library databases were conducted most recently in March 2019. The searches identified 281 citations, which were reviewed in abstract form. Of these, 48 were selected for a full-text review, and 13 met the inclusion criteria and were assigned a quality-of-evidence rating by the panel methodologist. Eight of these studies were rated level II and 5 were rated level III; there were no level I studies. RESULTS This analysis included 10 studies of the use of autologous serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight of the studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all of the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. CONCLUSIONS Although autologous serum-based tears may be effective in the treatment of severe dry eye and persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.
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